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Peripheral Neuropathy Phenotyping in Rat Models of Type 2 Diabetes Mellitus: Evaluating Uptake of the Neurodiab Guidelines and Identifying Future Directions
Md Jakir Hossain, Michael D. Kendig, Meg E. Letton, Margaret J. Morris, Ria Arnold
Diabetes Metab J. 2022;46(2):198-221.   Published online March 24, 2022
DOI: https://doi.org/10.4093/dmj.2021.0347
  • 5,474 View
  • 227 Download
  • 4 Web of Science
  • 4 Crossref
AbstractAbstract PDFPubReader   ePub   
Diabetic peripheral neuropathy (DPN) affects over half of type 2 diabetes mellitus (T2DM) patients, with an urgent need for effective pharmacotherapies. While many rat and mouse models of T2DM exist, the phenotyping of DPN has been challenging with inconsistencies across laboratories. To better characterize DPN in rodents, a consensus guideline was published in 2014 to accelerate the translation of preclinical findings. Here we review DPN phenotyping in rat models of T2DM against the ‘Neurodiab’ criteria to identify uptake of the guidelines and discuss how DPN phenotypes differ between models and according to diabetes duration and sex. A search of PubMed, Scopus and Web of Science databases identified 125 studies, categorised as either diet and/or chemically induced models or transgenic/spontaneous models of T2DM. The use of diet and chemically induced T2DM models has exceeded that of transgenic models in recent years, and the introduction of the Neurodiab guidelines has not appreciably increased the number of studies assessing all key DPN endpoints. Combined high-fat diet and low dose streptozotocin rat models are the most frequently used and well characterised. Overall, we recommend adherence to Neurodiab guidelines for creating better animal models of DPN to accelerate translation and drug development.

Citations

Citations to this article as recorded by  
  • SIRT3 alleviates painful diabetic neuropathy by mediating the FoxO3a‐PINK1‐Parkin signaling pathway to activate mitophagy
    Jing Yang, Zhuoying Yu, Ye Jiang, Zixian Zhang, Yue Tian, Jie Cai, Min Wei, Yanhan Lyu, Dongsheng Yang, Shixiong Shen, Guo‐Gang Xing, Min Li
    CNS Neuroscience & Therapeutics.2024;[Epub]     CrossRef
  • Compound Qiying Granules alleviates diabetic peripheral neuropathy by inhibiting endoplasmic reticulum stress and apoptosis
    Yan Hu, Chen Chen, Zhengting Liang, Tao Liu, Xiaoling Hu, Guanying Wang, Jinxia Hu, Xiaolin Xie, Zhiyan Liu
    Molecular Medicine.2023;[Epub]     CrossRef
  • HCV affects KATP channels through GnT-IVa-mediated N-glycosylation of GLUT2 on the surface of pancreatic β-cells leading to impaired insulin secretion
    Ben Niu, Lijing Ma, Lixuan Yao, Yating Zhang, Heng Su
    Endocrine.2023; 84(2): 427.     CrossRef
  • Multimodal Comparison of Diabetic Neuropathy in Aged Streptozotocin-Treated Sprague–Dawley and Zucker Diabetic Fatty Rats
    Annalisa Canta, Valentina A. Carozzi, Alessia Chiorazzi, Cristina Meregalli, Norberto Oggioni, Virginia Rodriguez-Menendez, Barbara Sala, Roberto Cosimo Melcangi, Silvia Giatti, Raffaella Lombardi, Roberto Bianchi, Paola Marmiroli, Guido Cavaletti
    Biomedicines.2022; 11(1): 20.     CrossRef
Short Communication
Others
Synthesis of a New Zinc-Mixed Ligand Complex and Evaluation of Its Antidiabetic Properties in High Fat Diet: Low Dose Streptozotocin Induced Diabetic Rats
Muruganantham Koothappan, Roshana Devi Vellai, Iyyam Pillai Subramanian, Sorimuthu Pillai Subramanian
Diabetes Metab J. 2018;42(3):244-248.   Published online April 24, 2018
DOI: https://doi.org/10.4093/dmj.2018.0002
  • 3,848 View
  • 50 Download
  • 4 Web of Science
  • 4 Crossref
AbstractAbstract PDFPubReader   

Due to the multifactorial and multisystemic nature of diabetes mellitus, it is often treated with a combination of therapeutic agents having different mode of action. Earlier, we have synthesized several organozinc complexes and evaluated their safety and antidiabetic properties in experimental type 2 diabetes mellitus (T2DM). More recently, we have synthesized a metformin-3-hydroxyflavone complex and studied its antidiabetic efficacy in experimental rats. In the present study, a new zinc-mixed ligand (metformin-3-hydroxyflavone) was synthesized, characterized by spectral studies and its antidiabetic properties was evaluated in HFD fed—low dose streptozotocin induced T2DM in rats. The hypoglycemic efficacy of the complex was evaluated through oral glucose tolerance test, homeostasis model assessment of insulin resistance, quantitative insulin sensitivity check index and by determining the status of important biochemical parameters. Oral administration of the complex at a concentration of 10 mg/kg body weight/rat/day for 30 days significantly improved the glucose homeostasis. The complex possesses significant antidiabetic properties relatively at a less concentration than metformin-3-hydroxyflavone complex in ameliorating hyperglycemia.

Citations

Citations to this article as recorded by  
  • Metformin compounds: A review on the importance and the possible applications
    A H Ismail, Z S Al-Garawi, K Al-Shamari, A T Salman
    Journal of Physics: Conference Series.2021; 1853(1): 012060.     CrossRef
  • A Review on Natural Products and Herbs Used in the Management of Diabetes
    Deepshikha Patle, Manish Vyas, Gopal L. Khatik
    Current Diabetes Reviews.2021; 17(2): 186.     CrossRef
  • The role of activation of KАTP channels on hydrogen sulfide induced renoprotective effect on diabetic nephropathy
    Eman A. Elbassuoni, Neven M. Аziz, Wagdу N. Habeeb
    Journal of Cellular Physiology.2020; 235(6): 5223.     CrossRef
  • A comprehensive review on zinc(II) complexes as anti-diabetic agents: The advances, scientific gaps and prospects
    Chika Ifeanyi Chukwuma, Samson S. Mashele, Kenneth C. Eze, Godfrey R. Matowane, Shahidul Md. Islam, Susanna L. Bonnet, Anwar E.M. Noreljaleel, Limpho M. Ramorobi
    Pharmacological Research.2020; 155: 104744.     CrossRef
Original Articles
Obesity and Metabolic Syndrome
Beneficial Effects of Aerobic Exercise Training Combined with Rosiglitazone on Glucose Metabolism in Otsuka Long Evans Tokushima Fatty Rats
Shan-Ji Piao, So Hun Kim, Young Ju Suh, Seong-Bin Hong, Seong Hee Ahn, Da Hae Seo, In-Sun Park, Moonsuk Nam
Diabetes Metab J. 2017;41(6):474-485.   Published online November 15, 2017
DOI: https://doi.org/10.4093/dmj.2017.41.6.474
  • 3,912 View
  • 39 Download
  • 2 Web of Science
  • 2 Crossref
AbstractAbstract PDFPubReader   
Background

Regular aerobic exercise is essential for the prevention and management of type 2 diabetes mellitus and may be particularly beneficial for those treated with thiazolidinediones, since it may prevent associated weight gain. This study aimed to evaluate the effect of combined exercise and rosiglitazone treatment on body composition and glucose metabolism in obese diabetes-prone animals.

Methods

We analyzed metabolic parameters, body composition, and islet profiles in Otsuka Long Evans Tokushima Fatty rats after 28 weeks of aerobic exercise, rosiglitazone treatment, and combined exercise and rosiglitazone treatment.

Results

Combined exercise with rosiglitazone showed significantly less increase in weight and epididymal fat compared to rosiglitazone treatment. Aerobic exercise alone and combined rosiglitazone and exercise treatment led to similar retention of lean body mass. All experimental groups showed a decrease in fasting glucose. However, the combined exercise and rosiglitazone therapy group showed prominent improvement in glucose tolerance compared to the other groups. Rescue of islet destruction was observed in all experimental groups, but was most prominent in the combined therapy group.

Conclusion

Regular aerobic exercise combined with rosiglitazone treatment can compensate for the adverse effect of rosiglitazone treatment and has benefit for islet preservation.

Citations

Citations to this article as recorded by  
  • Impacts of an Exercise Intervention on the Health of Pancreatic Beta-Cells: A Review
    Shuang Zhang, Yaru Wei, Chunxiao Wang
    International Journal of Environmental Research and Public Health.2022; 19(12): 7229.     CrossRef
  • Molecular mechanisms by which aerobic exercise induces insulin sensitivity
    Habib Yaribeygi, Stephen L. Atkin, Luis E. Simental‐Mendía, Amirhossein Sahebkar
    Journal of Cellular Physiology.2019; 234(8): 12385.     CrossRef
Pathophysiology
Protective Effects of Ginger (Zingiber officinale) Extract against Diabetes-Induced Heart Abnormality in Rats
Behrouz Ilkhanizadeh, Alireza Shirpoor, Mohamad hasan Khadem Ansari, Samira Nemati, Yusef Rasmi
Diabetes Metab J. 2016;40(1):46-53.   Published online February 19, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.1.46
  • 4,820 View
  • 71 Download
  • 34 Web of Science
  • 25 Crossref
AbstractAbstract PDFPubReader   
Background

Diabetic cardiomyopathy is an important causal factor in morbidity and mortality among diabetic patients, and currently, no effective means are available to reverse its pathological progress. The purpose of the present study was to investigate the effect of ginger extract on apolipoproteins (apo) A and B, hyperhomocysteinemia, cathepsin G and leptin changes, as well as cardiac fibrosis and heart muscle cell proliferation under hyperglycemic conditions in vivo.

Methods

Twenty-four male Wistar rats were divided into three groups, namely: control, non-treated diabetic, and ginger extract-treated diabetic groups. The ginger extract-treated diabetic group received a 50 mg daily dose of ginger extract intragastrically for 6 weeks.

Results

The results revealed concurrent significant increases in plasma C-reactive protein (CRP), homocysteine (Hcy), cathepsin G and apoB levels and decreases in apoA and leptin levels in the non-treated diabetic group compared to the control group. Moreover, heart structural changes, including fibrosis and heart muscle cell proliferation, were observed in non-treated diabetic rats compared to the control rats. Significant amelioration of changes in the heart structure together with restoration of the elevated levels of Hcy and CRP, leptin, cathepsin G, and apoA and B were found in the ginger extract-treated diabetic group compared to the non-treated diabetic group.

Conclusion

The findings indicated that ginger extract significantly reduces heart structural abnormalities in diabetic rats and that these effects might be associated with improvements in serum apo, leptin, cathepsin G, and Hcy levels and with the antioxidant properties of ginger extract.

Citations

Citations to this article as recorded by  
  • Cardioprotective Activities of some Indian Spices: An Insight into Pharmacology and Phytochemical Investigation
    Kalyani Pathak, Manash Pratim Pathak, Riya Saikia, Urvashee Gogoi, Jon Jyoti Sahariah, Aparoop Das, Mohammad Zaki Ahmad, Tirna Paul, Jyotirmoy Das, Saif Aboud M. Alqahtani
    Current Traditional Medicine.2024;[Epub]     CrossRef
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    Ling Yang, Yang Jian, Zai-Yuan Zhang, Bao-Wen Qi, Yu-Bo Li, Pan Long, Yao Yang, Xue Wang, Shuo Huang, Jing Huang, Long-Fu Zhou, Jie Ma, Chang-Qing Jiang, Yong-He Hu, Wen-Jing Xiao
    World Journal of Diabetes.2023; 14(7): 1057.     CrossRef
  • Evaluating the effect of Ginger Powder on Bilirubin, Creatinine, Urea and Uric Acid on Experimental Diabetic Wistar Rats in Randomized Control Trial
    Maryam Maqsood, Saima Naaz, Huma Bader Ul Ain, Zunaira Mushtaq, Makia Nasir, Aiza Qamar
    Pakistan BioMedical Journal.2022; 5(1): 351.     CrossRef
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    Titin Sulastri, Marleen Sunyoto, Marvel Reuben Suwitono, Jutti Levita
    Journal Of Advanced Pharmacy Education And Research.2022; 12(3): 28.     CrossRef
  • Protective effects of medicinal plant against diabetes induced cardiac disorder: A review
    Sadegh Shabab, Zahra Gholamnezhad, Maryam Mahmoudabady
    Journal of Ethnopharmacology.2021; 265: 113328.     CrossRef
  • Ginger (Zingiber Officinale Roscoe) Extract Protects the Heart Against Inflammation and Fibrosis in Diabetic Rats
    Tara Abdi, Maryam Mahmoudabady, Hadi Zare Marzouni, Saeed Niazmand, Majid Khazaei
    Canadian Journal of Diabetes.2021; 45(3): 220.     CrossRef
  • Combined ginger and garlic extract improves serum lipid profile, oxidative stress markers and reduced IL-6 in diet induced obese rats
    Peter Ifeoluwa Adegbola, Olumide Samuel Fadahunsi, Bamidele Stephen Ajilore, Adebola Olayemi Akintola, Olubukola Sinbad Olorunnisola
    Obesity Medicine.2021; 23: 100336.     CrossRef
  • The Effects of Medicinal Plants and Bioactive Natural Compounds on Homocysteine
    Mohammad Amin Atazadegan, Mohammad Bagherniya, Gholamreza Askari, Aida Tasbandi, Amirhossein Sahebkar
    Molecules.2021; 26(11): 3081.     CrossRef
  • Long-chain noncoding RNA-GAS5/hsa-miR-138-5p attenuates high glucose-induced cardiomyocyte damage by targeting CYP11B2
    Xiaozhen Zhuo, Kai Bai, Yingxian Wang, Peining Liu, Wen Xi, Jianqing She, Junhui Liu
    Bioscience Reports.2021;[Epub]     CrossRef
  • Regulation of Apolipoprotein B by Natural Products and Nutraceuticals: A Comprehensive Review
    Mohammad Bagherniya, Thomas P. Johnston, Amirhossein Sahebkar
    Current Medicinal Chemistry.2021; 28(7): 1363.     CrossRef
  • Ameliorative effects of Hydrolea zeylanica in streptozotocin-induced oxidative stress and metabolic changes in diabetic rats
    Sandeep Kumar Swain, Umesh Chandra Dash, Satish Kanhar, Atish Kumar Sahoo
    Journal of Ethnopharmacology.2020; 247: 112257.     CrossRef
  • The effect of 8 weeks of high-intensity interval training and moderate-intensity continuous training on cardiac angiogenesis factor in diabetic male rats
    Faramarz Yazdani, Fereshteh Shahidi, Pouran Karimi
    Journal of Physiology and Biochemistry.2020; 76(2): 291.     CrossRef
  • DNA methyltransferase-1 inactivation of androgen receptor axis triggers homocysteine induced cardiac fibroblast autophagy in diabetic cardiac fibrosis
    Hui Tao, Peng Shi, Hai-Yang Xuan, Xuan-Sheng Ding
    Archives of Biochemistry and Biophysics.2020; 692: 108521.     CrossRef
  • Ameliorative and protective effects of ginger and its main constituents against natural, chemical and radiation-induced toxicities: A comprehensive review
    Muhammad A. Alsherbiny, Wessam H. Abd-Elsalam, Shymaa A. El badawy, Ehab Taher, Mohamed Fares, Allan Torres, Dennis Chang, Chun Guang Li
    Food and Chemical Toxicology.2019; 123: 72.     CrossRef
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    Оlena Ruban, Malek Alkhalaf, Nataliia Gerbina
    EUREKA: Health Sciences.2019; 3: 26.     CrossRef
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    Bindu Jacob, Narendhirakannan R.T.
    3 Biotech.2019;[Epub]     CrossRef
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    Nur Fatin Nabilah Mohd Sahardi, Suzana Makpol
    Evidence-Based Complementary and Alternative Medicine.2019; 2019: 1.     CrossRef
  • Roles of Spicy Foods and Their Bioactive Compounds in Management of Hypercholesterolemia
    Yimin Zhao, Zhen-Yu Chen
    Journal of Agricultural and Food Chemistry.2018; 66(33): 8662.     CrossRef
  • Relaxant and vasoprotective effects of ginger extracts on porcine coronary arteries
    Hsing‑Chen Wu, Chi‑Ting Horng, Shih‑Chang Tsai, You‑Li Lee, Shou‑Cheng Hsu, Yi‑Jen Tsai, Fuu‑Jen Tsai, Jo‑Hua Chiang, Daih‑Huang Kuo, Jai‑Sing Yang
    International Journal of Molecular Medicine.2018;[Epub]     CrossRef
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    Alireza Shirpoor, Elaheh Heshmati, Fatemeh Kheradmand, Farzaneh Hosseini Gharalari, Leila Chodari, Roya Naderi, Farideh Nezami Majd, Mahrokh Samadi
    Biomedicine & Pharmacotherapy.2018; 105: 144.     CrossRef
  • Ginger extract mitigates ethanol-induced changes of alpha and beta – myosin heavy chain isoforms gene expression and oxidative stress in the heart of male wistar rats
    Alireza Shirpoor, Mitra Zerehpoosh, Mohammad Hasan Khadem Ansari, Fatemeh Kheradmand, Yousef Rasmi
    DNA Repair.2017; 57: 45.     CrossRef
  • Single, repeated dose toxicity and genotoxicity assessment of herb formula KIOM2012H
    Hwayong Park, Youn-Hwan Hwang, Jin Yeul Ma
    Integrative Medicine Research.2017; 6(4): 361.     CrossRef
  • Rescue effects of ginger extract on dose dependent radiation-induced histological and biochemical changes in the kidneys of male Wistar rats
    Hassan Saberi, Behnaz Keshavarzi, Alireza Shirpoor, Farzaneh Hosseini Gharalari, Yousef Rasmi
    Biomedicine & Pharmacotherapy.2017; 94: 569.     CrossRef
  • Promising Antidiabetic Drugs, Medicinal Plants and Herbs: An Update
    Mohd Iqbal Yatoo, Archana Saxena, Arumugam Gopalakris, Mahmoud Alagawany, Kuldeep Dhama
    International Journal of Pharmacology.2017; 13(7): 732.     CrossRef
  • Cardioprotective effects of rutin via alteration in TNF-α, CRP, and BNP levels coupled with antioxidant effect in STZ-induced diabetic rats
    Ravi Saklani, Suresh Kumar Gupta, Ipseeta Ray Mohanty, Binit Kumar, Sushma Srivastava, Rajani Mathur
    Molecular and Cellular Biochemistry.2016; 420(1-2): 65.     CrossRef
Pathophysiology
The Preventive Effects of 8 Weeks of Resistance Training on Glucose Tolerance and Muscle Fiber Type Composition in Zucker Rats
Ji-yeon Kim, Mi Jung Choi, Byunghun So, Hee-jae Kim, Je Kyung Seong, Wook Song
Diabetes Metab J. 2015;39(5):424-433.   Published online October 22, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.5.424
  • 4,740 View
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  • 22 Web of Science
  • 24 Crossref
AbstractAbstract PDFPubReader   
Background

We investigated the therapeutic effects of resistance training on Zucker rats before and after the onset of diabetes to understand the importance of the timing of exercise intervention. We assessed whether 8 weeks of resistance training ameliorated impaired glucose tolerance and altered muscle fiber type composition in Zucker rats.

Methods

Five-week-old male Zucker rats were divided into Zucker lean control (ZLC-Con), non-exercised Zucker diabetic fatty (ZDF-Con), and exercised Zucker diabetic fatty (ZDF-Ex) groups. The ZDF-Ex rats climbed a ladder three times a week for 8 weeks. Intraperitoneal glucose tolerance tests (IPGTT) were performed on the 1st and 8th weeks of training, and grip strength was measured during the last week. We also measured glucose transporter 4 (GLUT4) expression by Western blot and immunofluorescence. Moreover, immunohistochemistry was performed to assess muscle fiber type composition.

Results

Fasting glucose levels and area under the curve responses to IPGTTs gradually increased as diabetes progressed in the ZDF-Con rats but decreased in the ZDF-Ex rats. Grip strength decreased in the ZDF-Con rats. However, resistance training did not improve grip strength in the ZDF-Ex rats. GLUT4 expression in the ZLC-Con and the ZDF-Con rats did not differ, but it increased in the ZDF-Ex rats. The proportions of myosin heavy chain I and II were lower and higher, respectively, in the ZDF-Con rats compared to the ZLC-Con rats. Muscle fiber type composition did not change in the ZDF-Ex rats.

Conclusion

Our results suggest that regular resistance training initiated at the onset of diabetes can improve glucose tolerance and GLUT4 expression without changing muscle morphology in Zucker rats.

Citations

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  • Aerobic and resistance exercises affect the BDNF/TrkB signaling pathway, and hippocampal neuron density of high-fat diet-induced obese elderly rats.
    Keshvari Maryam, Heidarianpour Ali
    Physiology & Behavior.2023; 264: 114140.     CrossRef
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    Yiyuan Zhang, Lu Chen, Jiefang Gao, Yahong Cheng, Fei Luo, Xinying Bai, Hong Ding
    European Journal of Nutrition.2023; 62(8): 3149.     CrossRef
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    Qing Wang, Heng Weng, Yue Xu, Hui Ye, Yongqi Liang, Lulu Wang, Yutong Zhang, Yujie Gao, Jiayi Wang, Yuchen Xu, Zhiling Sun, Guihua Xu
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    Hassan Tavassoli, Ali Heidarianpour, Mehdi Hedayati
    Archives of Physiology and Biochemistry.2022; 128(1): 240.     CrossRef
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    Michihiro Kon, Yasuhiro Suzuki
    Archives of Physiology and Biochemistry.2022; 128(1): 248.     CrossRef
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    Mio Shimomura, Naoki Horii, Shumpei Fujie, Kenichiro Inoue, Natsuki Hasegawa, Keiko Iemitsu, Masataka Uchida, Motoyuki Iemitsu
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    Oak‐Kee Hong, Yoon‐Hee Choi, Hyuk‐Sang Kwon, Hee‐Kyoung Jeong, Jang‐Won Son, Seong‐Su Lee, Sung‐Rae Kim, Kun‐Ho Yoon, Soon Jib Yoo
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    Dengqiu Xu, Zhenzhou Jiang, Zeren Sun, Lu Wang, Guolin Zhao, Hozeifa M. Hassan, Sisi Fan, Wang Zhou, Shuangshuang Han, Luyong Zhang, Tao Wang
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    Parker L. Evans, Shawna L. McMillin, Luke A. Weyrauch, Carol A. Witczak
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    Shan Hu, Yeqing Gu, Zuolin Lu, Qing Zhang, Li Liu, Ge Meng, Zhanxin Yao, Hongmei Wu, Xue Bao, Vu Thi Quynh Chi, Shunming Zhang, Mingyue Liu, Yanyan Wang, Liu Wang, Lixiao Zheng, Xiaona Wang, Chunling Tian, Jingzhu Fu, Shaomei Sun, Ming Zhou, Qiyu Jia, Kun
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    André Junior Santana, Jean Carlos Debastiani, Regina Inês Kunz, Pamela Buratti, Rose Meire Costa Brancalhão, Lucinéia de Fátima Chasko Ribeiro, Márcia Miranda Torrejais, Gladson Ricardo Flor Bertolini
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    Yeon-Hee Kim, Jin-Hwan Yoon, You-Mi Kim
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    Shawna L. McMillin, Denise L. Schmidt, Barbara B. Kahn, Carol A. Witczak
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    Carlos Eduardo C. Martins, Vanessa B. de S. Lima, Brad J. Schoenfeld, Julio Tirapegui
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    Megan E. Rosa‐Caldwell, Jacob L. Brown, David E. Lee, Thomas A. Blackwell, Kyle W. Turner, Lemuel A. Brown, Richard A. Perry, Wesley S. Haynie, Tyrone A. Washington, Nicholas P. Greene
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    Christopher W. MacDonell, Jeremy W. Chopek, Kalan R. Gardiner, Phillip F. Gardiner
    Journal of Neurophysiology.2017; 118(4): 2318.     CrossRef
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    Qimuge Siqin, Tadayuki Nishiumi, Takahisa Yamada, Shuiqing Wang, Wenjun Liu, Rihan Wu, Gerelt Borjigin
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    Jong Cheol Lee, Il Yong Kim, Yeri Son, Seul Kee Byeon, Dong Hyun Yoon, Jun Seok Son, Han Sol Song, Wook Song, Je Kyung Seong, Myeong Hee Moon
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Effect of Livingstone Potato (Plectranthus esculenthus N.E.Br) on Diabetes and Its Complications in Streptozotocin Induced Diabetes in Rats
Chinedum Ogbonnaya Eleazu, Kate Chinedum Eleazu, Adanma Ironkwe, Mercy Amarachi Iroaganachi
Diabetes Metab J. 2014;38(5):366-374.   Published online October 17, 2014
DOI: https://doi.org/10.4093/dmj.2014.38.5.366
  • 3,392 View
  • 30 Download
  • 5 Web of Science
  • 4 Crossref
AbstractAbstract PDFPubReader   
Background

The effect of livingstone potato (Plectranthus esculenthus N.E.Br) on diabetes and its complications in Streptozotocin induced diabetic rats was investigated. The duration of the experiment was 4 weeks.

Methods

The blood glucose level of the rats was measured with a glucometer, the protein and glucose and specific gravity in the urine samples of the rats were measured using urine assay strips and urinometer respectively. The liver and kidney function parameters in the serum of the rats were determined using Biosystem Kits.

Results

The diabetic rats given livingstonepotato incorporated feeds, had 129.7% decrease in their hyperglycemia with corresponding amelioration of their elevated urinary protein, sugars, specific gravity, renal growth, liver growth as well as 15.64% decrease in body weights compared with the nondiabetic rats that had 5.54% decrease in blood glucose and 20.39% increase in body weight unlike the diabetic control rats that had 18.34% decrease in blood glucose and 52.68% decrease in body weight. There were significant differences (P<0.05) in the relative liver, pancreas, and kidney weights of the diabetic rats given livingstone potato feeds compared with the diabetic control while there were no significant differences (P>0.05) in the relative heart weights of all the rats in the three different groups. In terms of liver and kidney function parameters, values obtained for the diabetic rats given livingstone potato incorporated feeds were not significantly different from that of the nondiabetic rats except for total bilurubin, aspartate transaminase, and creatinine (P>0.05) while they were significantly different from the values obtained for the diabetic control rats (P<0.05). In addition, the serum amylase of the diabetic control rats were significantly higher (P<0.05) than that of the nondiabetic and diabetic rats treated with livingstone potato incorporated feeds.

Conclusion

Results show the antidiabetic actions of livingstone potato and its ability to ameliorate glomerular complication and liver hypertrophy in diabetics.

Citations

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    CABI Compendium.2022;[Epub]     CrossRef
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Effect of Treadmill Exercise on Interleukin-15 Expression and Glucose Tolerance in Zucker Diabetic Fatty Rats
Hee-Jae Kim, Jae Young Park, Seung Lyul Oh, Yong-An Kim, Byunghun So, Je Kyung Seong, Wook Song
Diabetes Metab J. 2013;37(5):358-364.   Published online October 17, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.5.358
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AbstractAbstract PDFPubReader   
Background

Interleukin-15 (IL-15), a well-known myokine, is highly expressed in skeletal muscle and is involved in muscle-fat crosstalk. Recently, a role of skeletal muscle-derived IL-15 in the improvement of glucose homeostasis and insulin sensitivity has been proposed. However, little is known regarding the influence of endurance training on IL-15 expression in type 2 diabetic skeletal muscles. We investigated the effect of endurance exercise training on glucose tolerance and IL-15 expression in skeletal muscles using type 2 diabetic animal models.

Methods

Male Zucker diabetic fatty (ZDF) and ZDF lean control (ZLC) rats were randomly divided into three groups: sedentary ZLC, sedentary ZDF (ZDF-Con), and exercised ZDF (ZDF-Ex). The ZDF-Ex rats were forced to run a motor-driven treadmill for 60 minutes once a day 5 times per week for 12 weeks. Intraperitoneal glucose tolerance test (IPGTT) was performed after 12 weeks. Expression of IL-15 was measured using ELISA in extracted soleus (SOL) and gastrocnemius medial muscles.

Results

After 12 weeks of treadmill training, reduction of body weight was observed in ZDF-Ex compared to ZDF-Con rats. Glucose tolerance using IPGTT in diabetic rats was significantly improved in ZDF-Ex rats. Furthermore, the expression of IL-15 was significantly increased (P<0.01) only in the SOL of ZDF-Ex rats compared to ZDF-Con. Additionally, IL-15 expression in SOL muscles was negatively correlated with change of body weight (R=-0.424, P=0.04).

Conclusion

The present study results suggest that 12 weeks of progressive endurance training significantly improved glucose tolerance with concomitant increase of IL-15 expression in SOL muscles of type 2 diabetic rats.

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Effect of Eplerenone, a Selective Aldosterone Blocker, on the Development of Diabetic Nephropathy in Type 2 Diabetic Rats
Jae Hee Ahn, Ho Cheol Hong, Myong Jin Cho, Yoon Jung Kim, Hae Yoon Choi, Chai Ryoung Eun, Sae Jeong Yang, Hye Jin Yoo, Hee Young Kim, Ji A Seo, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi, Nan Hee Kim
Diabetes Metab J. 2012;36(2):128-135.   Published online April 17, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.2.128
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AbstractAbstract PDFPubReader   
Background

Aldosterone antagonists are reported to have beneficial effects on diabetic nephropathy by effective blocking of the renin-angiotensin-aldosterone system. We investigated the renoprotective effect of the selective aldosterone receptor blocker eplerenone, the angiotensin converting enzyme inhibitor lisinopril, and combined eplerenone and lisinopril treatment in type 2 diabetic rats.

Methods

Animals were divided into six groups as follows: Otsuka Long-Evans Tokushima Fatty (OLETF) rat control, OLETF rats treated with a low dose of eplerenone (50 mg/kg/day), OLETF rats treated with a high dose of eplerenone (200 mg/kg/day), OLETF rats treated with lisinopril (10 mg/kg/day), OLETF rats treated with a combination of both drugs (eplerenone 200 mg/kg/day and lisinopril 10 mg/kg/day), and obese non-diabetic Long-Evans Tokushima Otsuka rats for 26 weeks.

Results

Urinary albumin excretion was significantly lower in the lisinopril group, but not in the eplerenone group. Urinary albumin excretion was decreased in the combination group than in the lisinopril group. Glomerulosclerosis and renal expression of type I and type IV collagen, plasminogen activator inhibitor-1, transforming growth factor-β1, connective tissue growth factor, and fibronectin mRNA were markedly decreased in the lisinopril, eplerenone, and combination groups.

Conclusion

Eplerenone and lisinopril combination showed additional benefits on type 2 diabetic nephropathy compared to monotherapy of each drug.

Citations

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  • Up-Date on Diabetic Nephropathy
    Maria Chiara Pelle, Michele Provenzano, Marco Busutti, Clara Valentina Porcu, Isabella Zaffina, Lucia Stanga, Franco Arturi
    Life.2022; 12(8): 1202.     CrossRef
  • The role of free radical oxidation in the kidneys in the nephroprotective action of eplerenone, a mineralocorticoid receptor antagonist, in experimental diabetes mellitus
    A. Yu. Zharikov, S. O. Filinova, O. N. Mazko, O. G. Makarova, I. P. Bobrov, V. M. Bryukhanov
    Bulletin of Siberian Medicine.2021; 20(2): 29.     CrossRef
  • Effect of Mineralocorticoid Receptor Antagonism and ACE Inhibition on Angiotensin Profiles in Diabetic Kidney Disease: An Exploratory Study
    Johannes J. Kovarik, Christopher C. Kaltenecker, Oliver Domenig, Marlies Antlanger, Marko Poglitsch, Chantal Kopecky, Marcus D. Säemann
    Diabetes Therapy.2021; 12(9): 2485.     CrossRef
  • Diabetic nephropathy: An update on pathogenesis and drug development
    Vikram Rao A/L B Vasanth Rao, Sean Hong Tan, Mayuren Candasamy, Subrat Kumar Bhattamisra
    Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2019; 13(1): 754.     CrossRef
  • Effects of mineralocorticoid receptor antagonists on the progression of diabetic nephropathy
    Li‐Jing Sun, Yan‐Ni Sun, Jian‐Ping Shan, Geng‐Ru Jiang
    Journal of Diabetes Investigation.2017; 8(4): 609.     CrossRef
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    Anna Gromotowicz-Poplawska, Piotr Szoka, Patrycjusz Kolodziejczyk, Karol Kramkowski, Marzena Wojewodzka-Zelezniakowicz, Ewa Chabielska
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    Jing Xiao, Weijun Chen, Yijun Lu, Xiaoli Zhang, Chensheng Fu, Zhenwen Yan, Zhenxing Zhang, Zhibin Ye
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    Agnieszka Zakrzeska, Anna Gromotowicz-Popławska, Janusz Szemraj, Piotr Szoka, Wioleta Kisiel, Tomasz Purta, Irena Kasacka, Ewa Chabielska
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Effects of Rosiglitazone on Inflammation in Otsuka Long-Evans Tokushima Fatty Rats
Jin Woo Lee, Il Seong Nam-Goong, Jae Geun Kim, Chang Ho Yun, Se Jin Kim, Jung Il Choi, Young IL Kim, Eun Sook Kim
Korean Diabetes J. 2010;34(3):191-199.   Published online June 30, 2010
DOI: https://doi.org/10.4093/kdj.2010.34.3.191
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AbstractAbstract PDFPubReader   
Background

Inflammation plays a role in the response to metabolic stress in type 2 diabetes. However, the effects of rosiglitazone on inflammation of skeletal muscle have not been fully examined in type 2 diabetes.

Methods

We investigated the effects of the insulin-sensitizing anti-diabetic agent, rosiglitazone, on the progression of skeletal muscle inflammation in Otsuka Long-Evans Tokushima Fatty (OLETF) type 2 diabetic rats. We examined the expression of serologic markers (serum glucose, insulin and free fatty acid) and inflammatory cytokines (tumor-necrosis factor-α, interleukin [IL]-1β and IL-6) in OLETF rats from early to advanced diabetic stage (from 28 to 40 weeks of age).

Results

Serum glucose and insulin concentrations were significantly decreased in rosiglitazone-treated OLETF rats compared to untreated OLETF rats. Rosiglitazone treatment significantly decreased the concentrations of serum inflammatory cytokines from 28 to 40 weeks of age. The mRNA expression of various cytokines in skeletal muscle was reduced in rosiglitazone-treated OLETF rats compared with untreated OLETF rats. Furthermore, rosiglitazone treatment resulted in the downregulation of ERK1/2 phosphorylation and NF-κB expression in the skeletal muscle of OLETF rats.

Conclusion

These results suggest that rosiglitazone may improve insulin sensitivity with its anti-inflammatory effects on skeletal muscle.

Citations

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  • Rosiglitazone Elicits an Adiponectin-Mediated Insulin-Sensitizing Action at the Adipose Tissue-Liver Axis in Otsuka Long-Evans Tokushima Fatty Rats
    Jia Li, Yao-Ming Xue, Bo Zhu, Yong-Hua Pan, Yan Zhang, Chunxia Wang, Yuhao Li
    Journal of Diabetes Research.2018; 2018: 1.     CrossRef
  • Sirt1 and Sirt6 Mediate Beneficial Effects of Rosiglitazone on Hepatic Lipid Accumulation
    Soo Jin Yang, Jung Mook Choi, Eugene Chang, Sung Woo Park, Cheol-Young Park, Aimin Xu
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  • Beneficial effects of co-enzyme Q10 and rosiglitazone in fructose-induced metabolic syndrome in rats
    Suzan M. Mansour, Hala F. Zaki, Ezz-El-Din S. El-Denshary
    Bulletin of Faculty of Pharmacy, Cairo University.2013; 51(1): 13.     CrossRef
  • Chromium Picolinate and Rosiglitazone Improve Biochemical Derangement in a Rat Model of Insulin Resistance: Role of TNF-a and Leptin
    Suzan M. Mansour, Hala F. Zaki, Ezz-El-Din El-Denshar
    Pharmacologia.2013; 4(3): 186.     CrossRef
  • Angiotensin Receptor Blockade Increases Pancreatic Insulin Secretion and Decreases Glucose Intolerance during Glucose Supplementation in a Model of Metabolic Syndrome
    Ruben Rodriguez, Jose A. Viscarra, Jacqueline N. Minas, Daisuke Nakano, Akira Nishiyama, Rudy M. Ortiz
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    Sunil K. Panchal, Lindsay Brown
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  • Letter: Effects of Rosiglitazone on Inflammation in Otsuka Long-Evans Tokushima Fatty Rats (Korean Diabetes J 2010;34:191-9)
    Soo Jin Yang, Cheol-Young Park
    Korean Diabetes Journal.2010; 34(4): 261.     CrossRef
Protective Effects of Lithospermic Acid B on Diabetic Nephropathy in OLETF Rats Comparing with Amlodipine and Losartan.
Eun Seok Kang, Beom Seok Kim, Chul Hoon Kim, Gi Ho Seo, Seung Jin Han, Sung Wan Chun, Kyu Yeon Hur, Chul Woo Ahn, Hunjoo Ha, Mankil Jung, Bong Soo Cha, Hyun Chul Lee
Korean Diabetes J. 2008;32(1):10-20.   Published online February 1, 2008
DOI: https://doi.org/10.4093/kdj.2008.32.1.10
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AbstractAbstract PDF
BACKGROUND
Lithospermic acid B (LAB), an active component isolated from Salvia miltiorrhizae, has been reported to have renoprotective effects in type 1 and type 2 diabetic animal models. We examined the effects of LAB on the prevention of diabetic nephropathy compared with amlodipine, a calcium channel blocker, and losartan, an angiotensin receptor blocker, in Otsuka Long-Evans-Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. METHODS: LAB (20 mg/kg), amlodipine (10 mg/kg), or losartan (10 mg/kg) was given orally once daily to 10-week-old male OLETF rats for 28 weeks. RESULTS: None of LAB, losartan, and amlodipine exhibited effects on blood glucose levels. Treatment with amlodipine or losartan resulted in similar reductions in blood pressure; however, LAB was less effective in lowering blood pressure. Albuminuria was markedly suppressed by losartan and LAB, but not by amlodipine. LAB treatment decreased levels of renal lipid peroxidation, monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-beta1 (TGF-beta1). CONCLUSION: These results suggest that LAB has beneficial effects on the diabetic nephropathy in OLETF rats by decreasing oxidative stress and inflammation as potent as losartan.

Citations

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  • An Overview on Naturally Occurring Phytoconstituent: Lithospermic Acid
    Bhupesh Chander Semwal, Amjad Hussain, Sonia Singh
    The Natural Products Journal.2024;[Epub]     CrossRef
Thiazolidinediones on Insulin Resistance and Insulin Secretion in Obese Diabetic OLETF Rats.
Jung hyun Noh, Seung hyun Hong, Kyoung hee Lee, Kyoung Min Min, Tae young Yang, Myung shik Lee, Kwang won Kim, Moon kyu Lee
Korean Diabetes J. 2007;31(1):33-43.   Published online January 1, 2007
DOI: https://doi.org/10.4093/jkda.2007.31.1.33
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AbstractAbstract PDF
BACKGROUND
Thiazolidinediones are synthetic peroxisome proliferator-activated receptor-gamma agonists that decrease insulin resistance but, as in vitro and in vivo studies suggest, may have direct beneficial effects on pancreatic beta cells. Here, we investigated the effects of thiazolidinediones (TZDs) on the insulin resistance, beta-cell mass and insulin secretion in obese diabetic OLETF rats. METHODS: We studied insulin resistance (by hyperinsulinemic euglycemic clamp) and insulin secretion (by hyperglycemic clamp) in TZDs administered OLETF and LETO rats. Histologic alterations of the islets were observed and beta-cell mass was also measured by point counting method. RESULTS: Chronic administration of troglitazone (TGZ, 0.15%) or pioglitazone (PGZ, 0.02%) prevented the development of glucose intolerance in OLETF rats, as assessed by oral glucose tolerance test. There was significant difference in submaximal glucose infusion rate between TGZ-treated and untreated OLETF rats during euglycemic clamp studies at 24 weeks of age. At 16 and 24 weeks of ages, beta-cell mass significantly increased in TGZ-treated OLETF rats compared to untreated animals. At 19 weeks and 30 weeks of age, first-phase insulin secretion was not different in PGZ-treated OLETF rats from untreated OLETF rats during hyperglycemic clamp study. At 30 weeks of age, late-phase insulin secretion was decreased in PGZ-treated OLETF rats compared to untreated OLETF rats. The expression of alpha-smooth muscle actin, a marker of activated pancreatic stellate cells that are involved in the fibrosis of the pancreas, in the islets was suppressed by TGZ treatment at 24 weeks of age. CONCLUSION: The treatment of TGZ prevented the development of diabetes, and increased insulin sensitivity and pancreatic beta-cell mass in OLETF rats. These results might be related with the suppression of pancreatic stellate cells. Insulin secretion was not affected by PGZ treatment.
Effects of Caloric Restriction on the Expression of PGC-1 and PPARs mRNA in Liver of Otsuka Long-Evans Tokushima Fatty Rats.
Sang Yong Kim, Jin Hwa Kim, Hak Yeon Bae, Byoung Rai Lee
Korean Diabetes J. 2006;30(3):161-169.   Published online May 1, 2006
DOI: https://doi.org/10.4093/jkda.2006.30.3.161
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AbstractAbstract PDF
BACKGROUND
Gluconeogenesis is strongly stimulated during fasting and is aberrantly activated in diabetes mellitus. PPARgamma-coactivator 1 (PGC-1) and Peroxisome proliferator -activated receptors (PPARs) costimulate the expression of key enzymes of gluconeogenetic pathway. This study was performed to evaluate the response to dietary caloric restriction (CR) on the PPARs and PGC-1 expression in liver of diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. METHODS: Diabetic OLETF rats (male, 24 weeks) and Long-Evans Tokushima Otsuka (LETO) rats (male, 24 weeks) were used in this study. Liver PPARs and PGC-1 mRNA, and blood glucose levels were investigated at 1, 2, and 3 weeks after the beginning of 30% CR. PPARs and PGC-1 mRNA were determined by RT-PCR and blood glucose levels were measured by spectrophotometric assay. RESULTS: The liver PGC-1 mRNA expressions were increased to 19% in non-diabetic LETO rats but significant change was not observed in diabetic OLETF rats by 30% CR. The liver PPARgamma mRNA expressions were not changed in non-diabetic LETO rats but increased to 23% in diabetic OLETF rats by 30% CR. The difference of PPARalpha and PPARbeta mRNA expressions in liver of OLETF and LETO rats were not observed. CONCLUSION: The liver PPARgamma and PGC-1 expression response to CR are altered in OLETF rats compared to in LETO rats. These findings suggested that PPARgamma and PGC-1 expression control system altered in diabetic OLETF rat liver and altered PPARgamma and PCG-1 expression may some roles on the aberrantly activated gluconeogenesis in diabetes mellitus.
Protective Effects of Lithospermate B on Diabetic Nephropathy in OLETF Rat.
Hyun Joo Lee, Geun Taek Lee, Eun Seok Kang, Kyu Yeon Hur, Zheng Shan Zhao, Chul Woo Ahn, Hun Joo Ha, Man Kil Jung, Bong Soo Cha, Hyun Chul Lee
Korean Diabetes J. 2005;29(4):322-332.   Published online July 1, 2005
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AbstractAbstract PDF
BACKGROUND
Magnesium lithospermate B(LAB), an active component isolated from Salvia milltiorrhizae, has been reported to have renoprotective effects in type 1 diabetic animal model. The purpose of this study was to examine the effects of LAB on the prevention of diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty(OLETF) rat which is regarded as an animal model of type 2 diabetes. METHODS: Ten microgram of LAB/kg or Vehicle(PBS) was given orally once daily to 10-week-old male OLETF rats and LETO rats for 40 weeks. Intra-peritoneal glucose tolerance test was performed at 50 weeks. 24 hr urinary protein excretion amounts were measured. Lipid peroxidation, TGF-beta1 and ED-1 of renal cortex were measured. RESULTS: The mean body weight of LAB+OLETF was not significantly different from that of OLETF rats. LAB treatment decreased proteinuria, lipid peroxidation, and free fatty acid in OLETF rats without decrease in the plasma glucose concentration. Also, LAB inhibited the progression of glomerular hypertrophy and mesangial expansion. LAB effectively decreased ED-1 positive cells, ECM expansion, and TGF-beta1 level in the renal cortex of OLETF rats. CONCLUSIONS: These results suggest that the beneficial effects of LAB on the diabetic renal damage in the OLETF rats may depend on a mechanism of decreasing oxidative stress. LAB might be a new therapeutic agent for the prevention of nephropathy in type 2 diabetes as well as type 1 diabetes.
High Carbohydrate Diet Effects on the Development of Diabetes Mellitus and Modification of Pancreatic Islets in OLETF Rats.
Sung Ki Kim, Seong Bin Hong, Hwi Ra Park, Eun A Kim, Kyung Wook Lee, Moon Suk Nam, Yong Seong Kim
Korean Diabetes J. 2004;28(3):187-198.   Published online June 1, 2004
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BACKGROUND
Diet has long been believed to be an important risk factor for type 2 diabetes. The composition of carbohydrates in the diet was higher in the past, where as now it is considerably reduced in the diet of Korean peoples, which is probably associated with the risk of developing type 2 diabetes. The aim of the present study was to investigate the long-term effect of high carbohydrate/low protein diets on the glucose and lipid metabolism and the pancreatic islet in OLETF(Otsuka Long-Evans Tokushima Fatty) rats, the animal model of type 2 diabetes. METHODS: Seven week old male OLETF rat were fed a high carbohydrate/low protein diet(carbohydrate 71.0%, fat 14.5%, protein 14.5%) as the experimental group, with an ordinary chow diet(carbohydrate 63.5%, fat 14.5%, protein 22%) fed to the controls. The plasma insulin, lipid profiles, free fatty acid and oral glucose tolerance were analyzed at 16 and 32 weeks. After the glucose tolerance test, the pancreas was excised, and immunohistochemical staining was conducted for the islet morphology and insulin mRNA to quantify the insulin secretory capacity. RESULTS: The basal glucose levels tended to be higher in the control group, but with no significant statistical difference. There were no differences in the serum insulin, total cholesterol, triglyceride, HDL-cholesterol and plasma free fatty acid levels between the two groups. The pancreatic islets of the control group showed multilobulation, with fibrotic changes; where as those of the experimental group were maintained normal profiles. A higher expression of insulin mRNA was observed in the experimental than in the control group. CONCLUSION: A high carbohydrate diet induced lower body weight increases, and protected against beta cell injury and decreased the development of abnormal glucose tolerance in OLETF rats. This may explain the growing incidence of diabetes with respect to the change in carbohydrate composition in the diet of Korean peoples. However, whether the protective effect of a high carbohydrate diet, against the development of diabetes in OLETF rats, can be attributed to small weight increases or if the change in food composition itself, or both needs to be determined.
Effect of Red Ginseng Extract on Lipid Peroxidation in Streptozotocin-induced Diabetic Rats.
Hee Jong Jin, Sung Hee Ihm, Ja Hei Ihm
Korean Diabetes J. 2001;25(5):374-383.   Published online October 1, 2001
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BACKGROUND
Diabetes mellitus is postulated to be associated with increased oxidative stress and lipid peroxidation which may contribute to vascular complications. Recently ginseng (Panax) has been shown to have an antioxidant effect by enhancing nitric oxide synthesis in endothelial cells and by directly scavenging hydroxyl radicals. It is unknown whether ginseng might act as an antioxidant against lipid peroxidation in diabetes. METHODS: We studied the in vitro effect of red ginseng extract on lipid peroxidation employing phospholipid liposome and low-density lipoprotein (LDL) as a model system. To investigate the in vivo effect on lipid peroxidation in diabetes, we administered red ginseng extract (1 g/L in drinking water) to streptozotocin (STZ)- induced diabetic rats for 12 weeks and measured lipid peroxidation products in plasma, liver, kidneys and heart. RESULTS: The Fe(3+)- or Cu(2+)- mediated lipid peroxidation in phospholipid liposome and LDL, measured by the concentration of TBARS, was inhibited in the presence of red ginseng extract. MDA level in plasma measured by HPLC was higher in STZ-induced diabetic rats than in control rats. Plasma MDA level was lower by 41% in red ginseng-treated diabetic rats than in untreated diabetic rats. Tissue MDA levels measured by TBA method in liver, kidneys and heart were higher in STZ-induced diabetic rats than in control rats. In red ginseng-treated diabetic rats tissue MDA levels were lower by 14~30% than in untreated diabetic rats. CONCLUSION: We observed that red ginseng extract has an effect in inhibiting lipid peroxidation both in vitro and in STZ-induced diabetic rats. These results suggest that red ginseng might have a beneficial effect in diabetes as an antioxidant against lipid peroxidation and diabetic vascular complications.

Diabetes Metab J : Diabetes & Metabolism Journal