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Renoprotective Effect of Gemigliptin, a Dipeptidyl Peptidase-4 Inhibitor, in Streptozotocin-Induced Type 1 Diabetic Mice
Gwon-Soo Jung, Jae-Han Jeon, Mi Sun Choe, Sung-Woo Kim, In-Kyu Lee, Mi-Kyung Kim, Keun-Gyu Park
Diabetes Metab J. 2016;40(3):211-221.   Published online March 31, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.3.211
  • 6,476 View
  • 54 Download
  • 22 Web of Science
  • 22 Crossref
AbstractAbstract PDFPubReader   
Background

Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used in the treatment of patients with type 2 diabetes and have proven protective effects on diabetic kidney disease (DKD). Whether DPP-4 inhibitors have renoprotective effects on insulin-deficient type 1 diabetes has not been comprehensively examined. The aim of this study was to determine whether gemigliptin, a new DPP-4 inhibitor, has renoprotective effects in streptozotocin (STZ)-induced type 1 diabetic mice.

Methods

Diabetes was induced by intraperitoneal administration of a single dose of STZ. Mice with diabetes were treated without or with gemigliptin (300 mg/kg) for 8 weeks. Morphological changes of the glomerular basement membrane (GBM) were observed by electron microscopy and periodic-acid Schiff staining. In addition, we measured blood glucose and urinary albumin excretion and evaluated fibrotic markers using immunohistochemical staining, quantitative reverse transcription polymerase chain reaction analysis, and Western blot analysis.

Results

Gemigliptin did not reduce the blood glucose levels of STZ-treated mice. In gemigliptin-treated mice with STZ, a significant reduction in urinary albumin excretion and GBM thickness was observed. Immunohistological examination revealed that gemigliptin attenuated renal fibrosis induced by STZ and decreased extracellular matrix protein levels, including those of type I collagen and fibronectin, and Smad3 phosphorylation. In cultured rat renal cells, gemigliptin inhibited transforming growth factor β-stimulated type I collagen and fibronectin mRNA and protein levels via down-regulation of Smad3 phosphorylation.

Conclusion

Our data demonstrate that gemigliptin has renoprotective effects on DKD, regardless of its glucose-lowering effect, suggesting that it could be used to prevent DKD, including in patients with type 1 diabetes.

Citations

Citations to this article as recorded by  
  • Diabetic fibrosis
    Izabela Tuleta, Nikolaos G. Frangogiannis
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2021; 1867(4): 166044.     CrossRef
  • Protective roles of thymoquinone and vildagliptin in manganese-induced nephrotoxicity in adult albino rats
    Heba El-Sayed Mostafa, Eman Ahmed Alaa El-Din, Dalia Abdallah El-Shafei, Nehal S. Abouhashem, Aisha Abdallah Abouhashem
    Environmental Science and Pollution Research.2021; 28(24): 31174.     CrossRef
  • Evogliptin, a Dipeptidyl Peptidase-4 Inhibitor, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice
    Mi-Jin Kim, Na-young Kim, Yun-A Jung, Seunghyeong Lee, Gwon-Soo Jung, Jung-Guk Kim, In-Kyu Lee, Sungwoo Lee, Yeon-Kyung Choi, Keun-Gyu Park
    Diabetes & Metabolism Journal.2020; 44(1): 186.     CrossRef
  • Gemigliptin Attenuates Renal Fibrosis Through Down-Regulation of the NLRP3 Inflammasome
    Jung Beom Seo, Yeon-Kyung Choi, Hye-In Woo, Yun-A Jung, Sungwoo Lee, Seunghyeong Lee, Mihyang Park, In-Kyu Lee, Gwon-Soo Jung, Keun-Gyu Park
    Diabetes & Metabolism Journal.2019; 43(6): 830.     CrossRef
  • Recent advances in the pathogenesis of microvascular complications in diabetes
    Sungmi Park, Hyeon-Ji Kang, Jae-Han Jeon, Min-Ji Kim, In-Kyu Lee
    Archives of Pharmacal Research.2019; 42(3): 252.     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
  • Mechanisms and pathways of anti‐inflammatory activity of DPP‐4 inhibitors in cardiovascular and renal protection
    Katarina Tomovic, Jelena Lazarevic, Gordana Kocic, Marina Deljanin‐Ilic, Marko Anderluh, Andrija Smelcerovic
    Medicinal Research Reviews.2019; 39(1): 404.     CrossRef
  • Effects of Dipeptidyl Peptidase-4 Inhibitors on Renal Outcomes in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis
    Jae Hyun Bae, Sunhee Kim, Eun-Gee Park, Sin Gon Kim, Seokyung Hahn, Nam Hoon Kim
    Endocrinology and Metabolism.2019; 34(1): 80.     CrossRef
  • The emerging role of novel antihyperglycemic agents in the treatment of heart failure and diabetes: A focus on cardiorenal outcomes
    Kelly R. McHugh, Adam D. DeVore, Robert J. Mentz, Daniel Edmonston, Jennifer B. Green, Adrian F. Hernandez
    Clinical Cardiology.2018; 41(9): 1259.     CrossRef
  • Acute Kidney Injury and Progression of Diabetic Kidney Disease
    Samuel Mon-Wei Yu, Joseph V. Bonventre
    Advances in Chronic Kidney Disease.2018; 25(2): 166.     CrossRef
  • Recombinant human GLP-1(rhGLP-1) alleviating renal tubulointestitial injury in diabetic STZ-induced rats
    Weiqin Yin, Shiqing Xu, Zai Wang, Honglin Liu, Liang Peng, Qing Fang, Tingting Deng, Wenjian Zhang, Jinning Lou
    Biochemical and Biophysical Research Communications.2018; 495(1): 793.     CrossRef
  • Chronic inhalation of e-cigarette vapor containing nicotine disrupts airway barrier function and induces systemic inflammation and multiorgan fibrosis in mice
    Laura E. Crotty Alexander, Christopher A. Drummond, Mark Hepokoski, Denzil Mathew, Alex Moshensky, Andrew Willeford, Soumita Das, Prabhleen Singh, Zach Yong, Jasmine H. Lee, Kevin Vega, Ashley Du, John Shin, Christian Javier, Jiang Tian, Joan Heller Brown
    American Journal of Physiology-Regulatory, Integrative and Comparative Physiology.2018; 314(6): R834.     CrossRef
  • Renoprotective effect of fucoidan from Acaudina molpadioides in streptozotocin/high fat diet-induced type 2 diabetic mice
    Shiwei Hu, Jinhui Wang, Jingfeng Wang, Shijie Li, Wei Jiang, Yu Liu
    Journal of Functional Foods.2017; 31: 123.     CrossRef
  • Dipeptidyl peptidase-4 inhibition and renoprotection
    Yuta Takagaki, Daisuke Koya, Keizo Kanasaki
    Current Opinion in Nephrology and Hypertension.2017; 26(1): 56.     CrossRef
  • Treatment of diabetic kidney disease: current and future targets
    Mi-Kyung Kim
    The Korean Journal of Internal Medicine.2017; 32(4): 622.     CrossRef
  • Pharmacological Treatment in Diabetes Mellitus Type 1 – Insulin and What Else?
    Ewa Otto-Buczkowska, Natalia Jainta
    International Journal of Endocrinology and Metabolism.2017;[Epub]     CrossRef
  • GLP-1 and the kidney: from physiology to pharmacology and outcomes in diabetes
    Marcel H. A. Muskiet, Lennart Tonneijck, Mark M. Smits, Michaël J.B. van Baar, Mark H. H. Kramer, Ewout J. Hoorn, Jaap A. Joles, Daniël H. van Raalte
    Nature Reviews Nephrology.2017; 13(10): 605.     CrossRef
  • Efficacy, safety and albuminuria‐reducing effect of gemigliptin in Korean type 2 diabetes patients with moderate to severe renal impairment: A 12‐week, double‐blind randomized study (the GUARD Study)
    Sun A. Yoon, Byoung G. Han, Sung G. Kim, Sang Y. Han, Young I. Jo, Kyung H. Jeong, Kook H. Oh, Hyeong C. Park, Sun H. Park, Shin W. Kang, Ki R. Na, Sun W. Kang, Nam H. Kim, Young H. Jang, Seong H. Shin, Dae R. Cha
    Diabetes, Obesity and Metabolism.2017; 19(4): 590.     CrossRef
  • Sodium butyrate has context-dependent actions on dipeptidyl peptidase-4 and other metabolic parameters
    Eun-Sol Lee, Dong-Sung Lee, Prakash Raj Pandeya, Youn-Chul Kim, Dae-Gil Kang, Ho-Sub Lee, Byung-Chul Oh, Dae Ho Lee
    The Korean Journal of Physiology & Pharmacology.2017; 21(5): 519.     CrossRef
  • Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor γ Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice
    Kwi-Hyun Bae, Jung Beom Seo, Yun-A Jung, Hye-Young Seo, Sun Hee Kang, Hui-Jeon Jeon, Jae Man Lee, Sungwoo Lee, Jung-Guk Kim, In-Kyu Lee, Gwon-Soo Jung, Keun-Gyu Park
    Endocrinology and Metabolism.2017; 32(1): 115.     CrossRef
  • Gemigliptin: An Update of Its Clinical Use in the Management of Type 2 Diabetes Mellitus
    Sung-Ho Kim, Jung-Hwa Yoo, Woo Je Lee, Cheol-Young Park
    Diabetes & Metabolism Journal.2016; 40(5): 339.     CrossRef
  • Risk assessment and management of post-transplant diabetes mellitus
    Eugene Han, Myoung Soo Kim, Yu Seun Kim, Eun Seok Kang
    Metabolism.2016; 65(10): 1559.     CrossRef
The Effect of DPP-4 Inhibitors on Metabolic Parameters in Patients with Type 2 Diabetes
Eun Yeong Choe, Yongin Cho, Younjeong Choi, Yujung Yun, Hye Jin Wang, Obin Kwon, Byung-Wan Lee, Chul Woo Ahn, Bong Soo Cha, Hyun Chul Lee, Eun Seok Kang
Diabetes Metab J. 2014;38(3):211-219.   Published online June 17, 2014
DOI: https://doi.org/10.4093/dmj.2014.38.3.211
  • 4,817 View
  • 72 Download
  • 27 Web of Science
  • 25 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   
Background

We evaluated the effects of two dipeptidyl peptidase-4 (DPP-4) inhibitors, sitagliptin and vildagliptin, on metabolic parameters in patients with type 2 diabetes mellitus.

Methods

A total of 170 type 2 diabetes patients treated with sitagliptin or vildagliptin for more than 24 weeks were selected. The patients were separated into two groups, sitagliptin (100 mg once daily, n=93) and vildagliptin (50 mg twice daily, n=77). We compared the effect of each DPP-4 inhibitor on metabolic parameters, including the fasting plasma glucose (FPG), postprandial glucose (PPG), glycated hemoglobin (HbA1c), and glycated albumin (GA) levels, and lipid parameters at baseline and after 24 weeks of treatment.

Results

The HbA1c, FPG, and GA levels were similar between the two groups at baseline, but the sitagliptin group displayed a higher PPG level (P=0.03). After 24 weeks of treatment, all of the glucose-related parameters were significantly decreased in both groups (P=0.001). The levels of total cholesterol and triglycerides were only reduced in the vildagliptin group (P=0.001), although the sitagliptin group received a larger quantity of statins than the vildagliptin group (P=0.002).The mean change in the glucose- and lipid-related parameters after 24 weeks of treatment were not significantly different between the two groups (P=not significant). Neither sitagliptin nor vildagliptin treatment was associated with a reduction in the high sensitive C-reactive protein level (P=0.714).

Conclusion

Vildagliptin and sitagliptin exert a similar effect on metabolic parameters, but vildagliptin exerts a more potent beneficial effect on lipid parameters.

Citations

Citations to this article as recorded by  
  • Insulin Tregopil: An Ultra-Fast Oral Recombinant Human Insulin Analog: Preclinical and Clinical Development in Diabetes Mellitus
    Shashank Joshi, Vathsala Jayanth, Subramanian Loganathan, Vasan K. Sambandamurthy, Sandeep N. Athalye
    Drugs.2023; 83(13): 1161.     CrossRef
  • Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study
    Jun Sung Moon, Sunghwan Suh, Sang Soo Kim, Heung Yong Jin, Jeong Mi Kim, Min Hee Jang, Kyung Ae Lee, Ju Hyung Lee, Seung Min Chung, Young Sang Lyu, Jin Hwa Kim, Sang Yong Kim, Jung Eun Jang, Tae Nyun Kim, Sung Woo Kim, Eonju Jeon, Nan Hee Cho, Mi-Kyung Ki
    Diabetes & Metabolism Journal.2021; 45(5): 675.     CrossRef
  • Vasculoprotective Effects of Vildagliptin. Focus on Atherogenesis
    Michał Wiciński, Karol Górski, Eryk Wódkiewicz, Maciej Walczak, Magdalena Nowaczewska, Bartosz Malinowski
    International Journal of Molecular Sciences.2020; 21(7): 2275.     CrossRef
  • Anti-inflammatory properties of antidiabetic drugs: A “promised land” in the COVID-19 era?
    Niki Katsiki, Ele Ferrannini
    Journal of Diabetes and its Complications.2020; 34(12): 107723.     CrossRef
  • Effect of Switching from Linagliptin to Teneligliptin Dipeptidyl Peptidase-4 Inhibitors in Older Patients with Type 2 Diabetes Mellitus


    Eugene Han, Minyoung Lee, Yong-ho Lee, Hye Soon Kim, Byung-wan Lee, Bong-Soo Cha, Eun Seok Kang
    Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2020; Volume 13: 4113.     CrossRef
  • Combined vildagliptin and memantine treatment downregulates expression of amyloid precursor protein, and total and phosphorylated tau in a rat model of combined Alzheimer’s disease and type 2 diabetes
    Samar S. Khalaf, Mohamed M. Hafez, Eman T. Mehanna, Noha M. Mesbah, Dina M. Abo-Elmatty
    Naunyn-Schmiedeberg's Archives of Pharmacology.2019; 392(6): 685.     CrossRef
  • Therapeutic experience of saxagliptin as first add-on after metformin in Indian type 2 diabetes patients: A non-interventional, prospective, observational study (ONTARGET-INDIA)
    Sanjay Kalra, Sarita Bajaj, AG Unnikrishnan, ManashP Baruah, Rakesh Sahay, V Hardik, Amit Kumar
    Indian Journal of Endocrinology and Metabolism.2019; 23(3): 312.     CrossRef
  • Cardiovascular Outcome Trials of the Incretin-Based Therapies: What Do We Know So Far?
    Pablo F. Mora, Eric L. Johnson
    Endocrine Practice.2017; 23(1): 89.     CrossRef
  • Treatment of Dyslipidemias to Prevent Cardiovascular Disease in Patients with Type 2 Diabetes
    Maryam Khavandi, Francisco Duarte, Henry N. Ginsberg, Gissette Reyes-Soffer
    Current Cardiology Reports.2017;[Epub]     CrossRef
  • Sodium butyrate has context-dependent actions on dipeptidyl peptidase-4 and other metabolic parameters
    Eun-Sol Lee, Dong-Sung Lee, Prakash Raj Pandeya, Youn-Chul Kim, Dae-Gil Kang, Ho-Sub Lee, Byung-Chul Oh, Dae Ho Lee
    The Korean Journal of Physiology & Pharmacology.2017; 21(5): 519.     CrossRef
  • Risk of Myopathy Associated With DPP-4 Inhibitors in Combination With Statins: A Disproportionality Analysis Using Data From the WHO and French Spontaneous Reporting Databases
    Vanessa Labat, Mickael Arnaud, Ghada Miremont-Salamé, Francesco Salvo, Bernard Bégaud, Antoine Pariente
    Diabetes Care.2017; 40(3): e27.     CrossRef
  • Soluble DPP-4 up-regulates toll-like receptors and augments inflammatory reactions, which are ameliorated by vildagliptin or mannose-6-phosphate
    Dong-Sung Lee, Eun-Sol Lee, Md. Morshedul Alam, Jun-Hyeog Jang, Ho-Sub Lee, Hyuncheol Oh, Youn-Chul Kim, Zahid Manzoor, Young-Sang Koh, Dae-Gil Kang, Dae Ho Lee
    Metabolism.2016; 65(2): 89.     CrossRef
  • A Multifactorial Approach to Reduce Cardiovascular Disease in Type 2 Diabetes Mellitus: Now More Than Ever
    Jan N. Basile
    Hospital Practice.2016; 44(1): 9.     CrossRef
  • Association between DPP4 gene polymorphism and serum lipid levels in Chinese type 2 diabetes individuals
    Xiaomin Xing, Yi Han, Xiaojun Zhou, Bo Zhang, Yan Li, Zhongsu Wang, Lin Liao, Lequn Su
    Neuropeptides.2016; 60: 1.     CrossRef
  • Common medications used by patients with type 2 diabetes mellitus: what are their effects on the lipid profile?
    Paul D. Rosenblit
    Cardiovascular Diabetology.2016;[Epub]     CrossRef
  • Dipeptidyl peptidase-4 inhibition and narrow-band ultraviolet-B light in psoriasis (DINUP): study protocol for a randomised controlled trial
    Maeve Lynch, Tomás B. Ahern, Irene Timoney, Cheryl Sweeney, Genevieve Kelly, Rosalind Hughes, Anne-Marie Tobin, Donal O’Shea, Brian Kirby
    Trials.2016;[Epub]     CrossRef
  • Efficacy of different dipeptidyl peptidase-4 (DPP-4) inhibitors on metabolic parameters in patients with type 2 diabetes undergoing dialysis
    Se Hee Park, Joo Young Nam, Eugene Han, Yong-ho Lee, Byung-Wan Lee, Beom Seok Kim, Bong-Soo Cha, Chul Sik Kim, Eun Seok Kang
    Medicine.2016; 95(32): e4543.     CrossRef
  • Incretin-based therapies for obesity treatment
    Aline Haas de Mello, Morgana Prá, Larissa Colonetti Cardoso, Rosiane de Bona Schraiber, Gislaine Tezza Rezin
    Metabolism.2015; 64(9): 967.     CrossRef
  • Brain Signaling Systems in the Type 2 Diabetes and Metabolic Syndrome: Promising Target to Treat and Prevent These Diseases
    Alexander O Shpakov, Kira V Derkach, Lev M Berstein
    Future Science OA.2015;[Epub]     CrossRef
  • Comparative analysis of therapeutic efficiency and costs (experience in Bulgaria) of oral antidiabetic therapies based on glitazones and gliptins
    Elena Pavlova Filipova, Katya Hristova Uzunova, Toni Yonkov Vekov
    Diabetology & Metabolic Syndrome.2015;[Epub]     CrossRef
  • Antidiabetic Effect of Galantamine: Novel Effect for a Known Centrally Acting Drug
    Mennatallah A. Ali, Hanan S. El-Abhar, Maher A. Kamel, Ahmed S. Attia, John Calvert
    PLOS ONE.2015; 10(8): e0134648.     CrossRef
  • The Nonglycemic Actions of Dipeptidyl Peptidase-4 Inhibitors
    Na-Hyung Kim, Taeyang Yu, Dae Ho Lee
    BioMed Research International.2014; 2014: 1.     CrossRef
  • A Post Hoc Analysis of HbA1c, Hypoglycemia, and Weight Change Outcomes with Alogliptin vs Glipizide in Older Patients with Type 2 Diabetes
    Morgan Bron, Craig Wilson, Penny Fleck
    Diabetes Therapy.2014; 5(2): 521.     CrossRef
  • Response: The Effect of DPP-4 Inhibitors on Metabolic Parameters in Patients with Type 2 Diabetes (Diabetes Metab J2014;38:211-9)
    EunYeong Choe, Eun Seok Kang
    Diabetes & Metabolism Journal.2014; 38(4): 319.     CrossRef
  • Letter: The Effect of DPP-4 Inhibitors on Metabolic Parameters in Patients with Type 2 Diabetes (Diabetes Metab J2014;38:211-9)
    Seung-Hwan Lee
    Diabetes & Metabolism Journal.2014; 38(4): 317.     CrossRef

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