Diabetes & Metabolism Journal

Review

Complications
Coronavirus Disease 2019 and Diabetes: The Epidemic and the Korean Diabetes Association Perspective: Junghyun Noh, Hyun-Ha Chang, In-Kyung Jeong, Kun Ho Yoon; Diabetes Metab J. 2020;44(3):372-381. Published online June 29, 2020; DOI: https://doi.org/10.4093/dmj.2020.0138

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Diabetes has been associated with more severe outcomes and higher mortality in coronavirus disease 2019 (COVID-19) patients compare to morbidity and mortality in patients without diabetes. Several mechanisms may play a role in this greater morbidity and mortality, especially uncontrolled hyperglycemia, an impaired immune system, pre-existing proinflammatory states, multiple comorbidities, and dysregulated angiotensin-converting enzyme 2 signaling. Thus, the diabetes medical community emergently needs to know about COVID-19 and its effects on patients with diabetes, as they must take precautions to carefully manage these patients during the COVID-19 pandemic. The Korean Diabetes Association provides some guidance and practical recommendations for the management of diabetes during the pandemic. This report provides insight into the association between diabetes and COVID-19, proper management of diabetes in patients with COVID-19 and an official suggestion by the Korean Diabetes Association for managing the COVID-19 outbreak.

Citations

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Medical comorbidities as predictors of COVID-19 short-term mortality: A historical cohort study in Indonesia
RizaldyTaslim Pinzon, Vanessa Veronica
Tzu Chi Medical Journal.2023; 35(1): 53. CrossRef
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Mina Khosravifar, Sogol Koolaji, Negar Rezaei, Ali Ghanbari, Seyedeh Melika Hashemi, Erfan Ghasemi, Ali Bitaraf, Ozra Tabatabaei‐Malazy, Nazila Rezaei, Sahar Mohammadi Fateh, Arezou Dilmaghani‐Marand, Rosa Haghshenas, Ameneh Kazemi, Erfan Pakatchian, Farz
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Yevgeniya Filippenko, Marianna Zagurovskaya, Aigul Abdrakhmanova, Saule Kassenova, Zhanar Zhakenova, Aizat Aimakhanova, Zhamilya Zholdybay
Egyptian Journal of Radiology and Nuclear Medicine.2022;[Epub] CrossRef
Being caught in the perfect storm of a diabetes epidemic and the COVID‐19 pandemic: What should we do for our patients?
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Journal of Diabetes Investigation.2021; 12(3): 297. CrossRef
COVID-19 associated with diabetes and other noncommunicable diseases led to a global health crisis
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Sang Chul Lee, Kang Ju Son, Chang Hoon Han, Seon Cheol Park, Ji Ye Jung
Scientific Reports.2021;[Epub] CrossRef
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Sang Youl Rhee, Jeongwoo Lee, Hyewon Nam, Dae-Sung Kyoung, Dong Wook Shin, Dae Jung Kim
Diabetes & Metabolism Journal.2021; 45(2): 251. CrossRef
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Hun-Sung Kim
Journal of Korean Medical Science.2021;[Epub] CrossRef
Nutritional information access and dietary behavior among people with diabetes during Covid-19 pandemic
Yovita Puri Subardjo, Gumintang Ratna Ramadhan, Dika Betaditya, Muflihatus Syarifah, Nurafifah Fauziana Abidin
IOP Conference Series: Earth and Environmental Science.2021; 746(1): 012027. CrossRef
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2021 Clinical Practice Guidelines for Diabetes Mellitus in Korea
Seung-Hyun Ko
The Journal of Korean Diabetes.2021; 22(4): 244. CrossRef
Clinical Characteristics and Mortality Predictors of COVID-19 Patients Hospitalized at Nationally-Designated Treatment Hospitals
Seong-Su Moon, Kwan Lee, Jungi Park, Seongcheol Yun, Yun Sik Lee, Dong Seok Lee
Journal of Korean Medical Science.2020;[Epub] CrossRef
Response: The Risk of Diabetes on Clinical Outcomes in Patients with Coronavirus Disease 2019: A Retrospective Cohort Study (Diabetes Metab J 2020;44:405–13)
Seung Min Chung, June Hong Ahn, Jun Sung Moon
Diabetes & Metabolism Journal.2020; 44(4): 625. CrossRef
Diabetes Mellitus and COVID-19
Jeong Hyun Park
The Journal of Korean Diabetes.2020; 21(3): 116. CrossRef

Original Articles

Complications
The Risk of Diabetes on Clinical Outcomes in Patients with Coronavirus Disease 2019: A Retrospective Cohort Study: Seung Min Chung, Yin Young Lee, Eunyeong Ha, Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee, Jian Hur, Kyung Soo Hong, Jong Geol Jang, Hyun Jung Jin, Eun Young Choi, Kyeong-Cheol Shin, Jin Hong Chung, Kwan Ho Lee, June Hong Ahn, Jun Sung Moon; Diabetes Metab J. 2020;44(3):405-413. Published online May 21, 2020; DOI: https://doi.org/10.4093/dmj.2020.0105

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Abstract PDF Supplementary Material PubReader

Background

To determine the role of diabetes mellitus (DM) in the coronavirus disease 2019 (COVID-19), we explored the clinical characteristics of patients with DM and compared risk factors such as age, glycemic control, and medications to those without DM.

Methods

This was a retrospective cohort study of 117 confirmed patients with COVID-19 which conducted at a tertiary hospital in Daegu, South Korea. The primary outcome was defined as the severe and critical outcome (SCO), of which the composite outcomes of acute respiratory distress syndrome, septic shock, intensive care unit care, and 28-day mortality. We analyzed what clinical features and glycemic control-related factors affect the prognosis of COVID-19 in the DM group.

Results

After exclusion, 110 participants were finally included. DM patients (n=29) was older, and showed higher blood pressure compared to non-DM patients. DM group showed higher levels of inflammation-related biomarkers and severity score, and highly progressed to SCO. After adjustment with other risk factors, DM increased the risk of SCO (odds ratio [OR], 10.771; P<0.001). Among the DM patients, SCO was more prevalent in elderly patients of ≥70 years old and age was an independent risk factor for SCO in patients with DM (OR, 1.175; P=0.014), while glycemic control was not. The use of medication did not affect the SCO, but the renin-angiotensin system inhibitors showed protective effects against acute cardiac injury (OR, 0.048; P=0.045).

Conclusion

The COVID-19 patients with DM had higher severity and resulted in SCO. Intensive and aggressive monitoring of COVID-19 clinical outcomes in DM group, especially in elderly patients is warranted.

Citations

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Risk phenotypes of diabetes and association with COVID-19 severity and death: an update of a living systematic review and meta-analysis
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COVID-19 and Cardiovascular Comorbidities
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Adithan Ganesh, Michael D. Randall
British Journal of Clinical Pharmacology.2022; 88(6): 2642. CrossRef
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Endocrinology, Diabetes & Metabolism.2022;[Epub] CrossRef
Glycated Albumin and Glycated Albumin/HbA1c Predict the Progression of Coronavirus Disease 2019 from Mild to Severe Disease in Korean Patients with Type 2 Diabetes
Jeongseon Yoo, Youngah Choi, Shin Ae Park, Ji Yeon Seo, Chul Woo Ahn, Jaehyun Han
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Novel Glycemic Index Based on Continuous Glucose Monitoring to Predict Poor Clinical Outcomes in Critically Ill Patients: A Pilot Study
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Jordan Loader, Frances C. Taylor, Erik Lampa, Johan Sundström
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Seong Ho Kim, Ji Young Kim, Eun Song Kim, Il Rae Park, Eun Yeong Ha, Seung Min Chung, Jun Sung Moon, Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee
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Jesús Chávez-Reyes, Carlos E. Escárcega-González, Erika Chavira-Suárez, Angel León-Buitimea, Priscila Vázquez-León, José R. Morones-Ramírez, Carlos M. Villalón, Andrés Quintanar-Stephano, Bruno A. Marichal-Cancino
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Risk phenotypes of diabetes and association with COVID-19 severity and death: a living systematic review and meta-analysis
Sabrina Schlesinger, Manuela Neuenschwander, Alexander Lang, Kalliopi Pafili, Oliver Kuss, Christian Herder, Michael Roden
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Valle Coronado-Vázquez, Maria del Valle Ramírez-Durán, Juan Gómez-Salgado, María Silvia Dorado-Rabaneda, Elena Benito-Alonso, Marina Holgado-Juan, Cristina Bronchalo-González
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Renin‐Angiotensin Aldosterone System Inhibitors in Primary Prevention and COVID‐19
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Letter: The Risk of Diabetes on Clinical Outcomes in Patients with Coronavirus Disease 2019: A Retrospective Cohort Study (Diabetes Metab J 2020;44:405–13)
So-Yeon Kim, Kyung-Soo Kim
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Response: The Risk of Diabetes on Clinical Outcomes in Patients with Coronavirus Disease 2019: A Retrospective Cohort Study (Diabetes Metab J 2020;44:405–13)
Seung Min Chung, June Hong Ahn, Jun Sung Moon
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The Clinical Characteristics and Outcomes of Patients with Moderate-to-Severe Coronavirus Disease 2019 Infection and Diabetes in Daegu, South Korea
Mi Kyung Kim, Jae-Han Jeon, Sung-Woo Kim, Jun Sung Moon, Nan Hee Cho, Eugene Han, Ji Hong You, Ji Yeon Lee, Miri Hyun, Jae Seok Park, Yong Shik Kwon, Yeon-Kyung Choi, Ki Tae Kwon, Shin Yup Lee, Eon Ju Jeon, Jin-Woo Kim, Hyo-Lim Hong, Hyun Hee Kwon, Chi Yo
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Min Cheol Chang, Jong-Moon Hwang, Jae-Han Jeon, Sang Gyu Kwak, Donghwi Park, Jun Sung Moon
Endocrinology and Metabolism.2020; 35(3): 595. CrossRef
Diabetes Mellitus and COVID-19
Jeong Hyun Park
The Journal of Korean Diabetes.2020; 21(3): 116. CrossRef
Management of Diabetes in Coronavirus Disease 2019: Prognosis and Practical Issues
Hye Soon Kim
The Journal of Korean Diabetes.2020; 21(3): 120. CrossRef
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Sun Joon Moon, Eun-Jung Rhee, Jin-Hyung Jung, Kyung-Do Han, Sung-Rae Kim, Won-Young Lee, Kun-Ho Yoon
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Jeong-Hoon Lim, Jang-Hee Cho, Yena Jeon, Ji Hye Kim, Ga Young Lee, Soojee Jeon, Hee Won Noh, Yong-Hoon Lee, Jaehee Lee, Hyun-Ha Chang, Hee-Yeon Jung, Ji-Young Choi, Sun-Hee Park, Chan-Duck Kim, Yong-Lim Kim, Shin-Woo Kim
Scientific Reports.2020;[Epub] CrossRef
Coronavirus Disease 2019 and Diabetes: The Epidemic and the Korean Diabetes Association Perspective
Junghyun Noh, Hyun-Ha Chang, In-Kyung Jeong, Kun Ho Yoon
Diabetes & Metabolism Journal.2020; 44(3): 372. CrossRef
Diabetes and COVID-19: Global and regional perspectives
In-Kyung Jeong, Kun Ho Yoon, Moon Kyu Lee
Diabetes Research and Clinical Practice.2020; 166: 108303. CrossRef

Epidemiology
Impact of Cytomegalovirus Disease on New-Onset Type 2 Diabetes Mellitus: Population-Based Matched Case-Control Cohort Study: Seul Gi Yoo, Kyung Do Han, Kyoung Hwa Lee, Yeonju La, Da Eun Kwon, Sang Hoon Han; Diabetes Metab J. 2019;43(6):815-829. Published online January 21, 2019; DOI: https://doi.org/10.4093/dmj.2018.0167

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Abstract PDF Supplementary Material PubReader

Background

A latent cytomegalovirus (CMV) cause chronic inflammation through undesirable inflation of cell-mediated immune response. CMV immunoglobulin G has been associated with cardiovascular disease and type 1 diabetes mellitus. We evaluated impact of CMV diseases on new-onset type 2 diabetes mellitus (T2DM).

Methods

From the Korean Health Insurance Review and Assessment Service claim database of entire population with 50 million, we retrieved 576 adult case group with CMV diseases diagnosed with International Statistical Classification of Diseases and Related-Health Problems 10th Revision (ICD-10) B25 code between 2010 and 2014 after exclusion of patients with T2DM to 2006. The 2,880 control patients without T2DM from 2006 to cohort entry point were selected between 2010 and 2014 by age, sex matching with case group. The subjects without new-onset T2DM were followed until 2015. T2DM, hypertension (HTN), dyslipidemia (DYS), and end-stage renal disease (ESRD) were coded as ICD-10.

Results

The frequency of new-onset T2DM in case group was significantly higher than that in control (5.6% vs. 2.2%, P<0.001). The group with T2DM (n=95) had higher incidence of CMV diseases than the group without T2DM (n=3,361) (33.7% vs. 16.2%, P<0.001). In multivariate regression model adjusted by age, sex, lower income, HTN, and DYS, the incidence rate (IR) of T2DM in case group was significantly higher than that in the control group (IR per 1,000, 19.0 vs. 7.3; odds ratio, 2.1; 95% confidence interval, 1.3 to 3.2). The co-existence of HTN, DYS, and ESRD with CMV diseases did not influence the IR of T2DM.

Conclusion

CMV diseases increase the patients' risk of developing T2DM.

Citations

Citations to this article as recorded by

An analysis of risk factors for spontaneously occurring type 2 diabetes mellitus in rhesus macaques (Macaca mulatta)
John P. Capitanio, Laura A. Del Rosso, JoAnn Yee, Marie‐Josee Marie‐France Lemoy
Journal of Medical Primatology.2024;[Epub] CrossRef
Virus-induced diabetes mellitus, revisiting infection etiology in light of SARS-CoV-2
Sundararaj Stanleyraj Jeremiah, Abu Saleh Md Moin, Alexandra E. Butler
Metabolism.2024; : 155917. CrossRef
Is Pollution the Primary Driver of Infectious Syndemics?
Merrill Singer
Pathogens.2024; 13(5): 370. CrossRef
Connecting the Dots: How Herpes Viruses Influence Type 2 Diabetes: Insights from Experimental Researches
Ushna Zameer, Eisha Saqib, Muhammad Salman Munshi, Samia Rohail
Clinical Medicine Insights: Endocrinology and Diabetes.2024;[Epub] CrossRef
Infections and immunity: associations with obesity and related metabolic disorders
Amitabha Ray, Melissa J. L. Bonorden, Rajashree Pandit, Katai J. Nkhata, Anupam Bishayee
Journal of Pathology and Translational Medicine.2023; 57(1): 28. CrossRef
The effects of cytomegalovirus on brain structure following sport-related concussion
Jonathan Savitz, Bryna D Goeckner, Bart N Ford, T Kent Teague, Haixia Zheng, Jaroslaw Harezlak, Rebekah Mannix, L Tugan Muftuler, Benjamin L Brett, Michael A McCrea, Timothy B Meier
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Does COVID-19 Infection Increase the Risk of Diabetes? Current Evidence
Rachel Wong, Emily Lam, Carolyn T. Bramante, Steven G. Johnson, Jane Reusch, Kenneth J. Wilkins, Hsin-Chieh Yeh
Current Diabetes Reports.2023; 23(8): 207. CrossRef
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Human MicroRNAs Attenuate the Expression of Immediate Early Proteins and HCMV Replication during Lytic and Latent Infection in Connection with Enhancement of Phosphorylated RelA/p65 (Serine 536) That Binds to MIEP
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Chong Jin Park, Seung Hun Sheen, Jeong Gyun Kim, Hakyung Kim, Yeo Song Kim, In-bo Han, Je Beom Hong, Chun Kee Chung, Seil Sohn
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Carmen Valentina Cristescu, Sophie Alain, Simona Maria Ruță
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Tamara Turk Wensveen, Dora Gašparini, Dario Rahelić, Felix M. Wensveen
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James S. Díaz, Fabián A. Jaimes
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T. N. Markova, M. A. Lysenko, A. A. Ivanova, E. S. Pavlova, A. A. Ponomareva, V. V. Chibisova, T. K. Isaev, D. O. Sinyavkin, A. M. Mkrtumyan
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Others
Factors Associated with Improved Glycemic Control by Direct-Acting Antiviral Agent Treatment in Egyptian Type 2 Diabetes Mellitus Patients with Chronic Hepatitis C Genotype 4: Alaaeldin Abdelsalam Dawood, Mohamed Zakarya Nooh, Ayman Abdelhaleem Elgamal; Diabetes Metab J. 2017;41(4):316-321. Published online August 22, 2017; DOI: https://doi.org/10.4093/dmj.2017.41.4.316

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33 Download
42 Web of Science
43 Crossref

Abstract PDF PubReader

Background

The association of chronic hepatitis C virus (HCV) infection with type 2 diabetes mellitus (T2DM) was first reported in 1994. Little is known about the effect of direct-acting antiviral agents (DAAs) on glycemic control in T2DM patients. The aim of the present study was to evaluate the factors associated with improved glycemic control (IGC) by DAA treatment in Egyptian T2DM patients with chronic HCV genotype 4 infection.

Methods

This study included 460 T2DM patients with chronic HCV genotype 4 infection. Four hundred patients received DAAs and 60 patients did not receive DAAs. Patients with sustained virological response after 3 months of DAAs (378 patients) were allocated into two groups: first group included 292 patients (77.2%) with IGC and second group included 86 patients (22.8%) with non-improved glycemic control (NIGC).

Results

In IGC group, 78 patients (26.7%) needed to decrease the dose of antidiabetic treatment. There were no significant differences between IGC and NIGC groups as regards age, sex, and body mass index. The percentage of patients with positive family history of T2DM, those with Child B class and duration of T2DM were significantly higher in NIGC group compared to IGC.

Conclusion

Diabetic patients receiving DAAs should be closely monitored for reduction of antidiabetic drugs especially insulin and sulfonylurea to avoid hypoglycemic events. Improvement of glycemic control with DAAs is more in patients without family history of T2DM, short duration of diabetes mellitus, and mild liver disease.

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Review

Functional and Mechanistic Integration of Infection and the Metabolic Syndrome: Peter Sommer, Gary Sweeney; Korean Diabetes J. 2010;34(2):71-76. Published online April 30, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.2.71

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Abstract PDF PubReader

The metabolic syndrome refers to a well defined group of risk factors, including central obesity and inflammation, for the development of diabetes and cardiovascular disease. Interestingly, many studies have recently led to the emergence of somewhat unexpected relationships between several infectious diseases and various aspects of the metabolic syndrome. Our understanding of the mechanisms underlying these interactions is also rapidly developing and some of these are summarized in this article. We will focus first on bacterial infection, and most notably the role of gut microbiota in regulaton of both obesity and inflammation. In particular, we focus on the role of inflammasomes and propose that understanding the role of Toll-like receptors and Nod-like receptors in the pathogenesis of inflammatory disorders with or without infection may provide novel targets for prevention and/or treatment of associated diseases. Secondly, chronic bacterial or viral infection and emerging links with metabolism will be reviewed. Finally, consideratons of biomarkers for metabolic syndrome, in particular lipocalin-2, and their link with infection will be discussed.

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Original Articles

Treatment of Type 1 Diabetes through Genetically Engineered K-cell Transplantation in a Mouse Model.: Ju Yeon Sim, Ju Hee Kim, Yu Bae Ahn, Ki Ho Song, Je Ho Han, Bong Yun Cha, Sook Kyung Lee, Sung Dae Moon; Korean Diabetes J. 2009;33(6):466-474. Published online December 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.6.466

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Abstract PDF: BACKGROUND
K-cells function as targets for insulin gene therapy. In a previous study, we constructed EBV-based plasmids expressing rat preproinsulin controlled by glucose-dependent insulinotropic polypeptide promoters. In the present study, we attempted to correct hyperglycemia in vivo using genetically engineered K-cells in a mouse model of type 1 diabetes. METHODS: K-cells expressing insulin were transplanted under the kidney capsules of STZ-induced diabetic mice. The blood glucose levels and body weights of the experimental animals were measured daily. After four weeks, the mice were injected intra-peritoneally with 2 g/kg glucose following a 6 hr fast. Blood glucose levels were measured immediately following glucose injections. All animals were sacrificed at the end of the glucose tolerance study, and pancreas and graft-bearing kidney tissue samples were stained with antibodies against insulin, glucagon, and C-peptide. RESULTS: The body weights of K-cell-transplanted diabetic mice increased after transplantation, whereas those of untreated diabetic control mice continued to decline. The blood glucose levels of K-cell-transplanted diabetic mice decreased gradually during the two weeks following transplantation. After intra-peritoneal injection of glucose into K-cell-transplanted diabetic mice, blood glucose levels increased at 30 minutes, and were restored to the normal range between 60 and 90 minutes, while untreated control diabetic mice continued to experience hyperglycemia. Kidney capsules containing transplanted K-cells were removed, and sections were stained with anti-insulin antibodies. We detected insulin-positive cells in the kidney capsules of K-cell-transplanted diabetic mice, but not in untreated control mice. CONCLUSION: We detected glucose-dependent insulin secretion in genetically engineered K-cells in a mouse model of type 1 diabetes. Our results suggest that genetically modified insulin producing K-cells may act as surrogate beta-cells to effectively treat type 1 diabetes.

Glucose-dependent Insulin Secretion from Genetically Engineered K-cells Using EBV-based Episomal Vector.: Ju Hee Kim, Sung Dae Moon, Seung Hyun Ko, Yu Bai Ahn, Ki Ho Song, Hyang Sook Lim, Sook Kyung Lee, Soon Jip Yoo, Hyun Shik Son, Kun Ho Yoon, Bong Yun Cha, Ho Young Son, Sung Joo Kim, Je Ho Han; Korean Diabetes J. 2007;31(1):9-21. Published online January 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.1.9

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Abstract PDF

BACKGROUND
Type 1 diabetes mellitus is an autoimmune disease resulting in destruction of the pancreatic beta cells. Insulin gene therapy for these patients has been vigorously researched. The strategy for achieving glucose-dependent insulin secretion in gene therapy relies on glucose-responsive transcription of insulin mRNA and the constitutive secretory pathway of target non-beta cells. We observed that genetically engineered K-cells using Epstein-Barr virus (EBV)-based episomal vector can produce glucose-regulated insulin production. METHODS: Green fluorescent protein (GFP) or rat-preproinsulin (PPI) expression cassette transcriptionally controlled by the promoter of glucose dependent insulinotropic peptide (GIPP) is fused to pCEP4 containing the origin of replication (oriP) and Epstein-Barr virus nuclear antigen 1 (EBNA-1). CMV promoter was replaced by subcloning the GIPP into pCEP4 to generate pGIPP/CEP4. Two recombinant EBV-based episomal vectors, pGIPP/GFP/CEP4 and pGIPP/PPI/CEP4, were constructed. pGIPP/GFP/CEP4 and pGIPP/PPI/CEP4 containing K-cell specific GIPP were co-transfected into STC-1. K-cell was isolated from the clonal expansion of the fluorescent cells selected by hygromycin treatment in STC-1, and were analyzed for the expression of glucokinase (GK) or transcription factors involved in pancreas development. K-cells concurrently transfected with pGIPP/PPI/CEP4 and pGIPP/GFP/CEP4 were analyzed for the transcripts of PPI by RT-PCR, and for the glucose dependent insulin expression by immunocytochemistry or insulin assay using ultra-sensitive rat-specific insulin ELISA kit. RESULT: STC-1 was stably-transfected with pGIPP/GFP/CEP4 along with pGIPP/PPI/CEP4. Genetically selected fluorescent K-cells expressed GK and transcription factors involved in pancreas development. And K-cells transfected with pGIPP/PPI/CEP4 contained detectable levels of PPI transcripts and showed glucose-dependent immunoreactive insulin secretion. CONCLUSION: We identified genetically engineered K-cells which exert a glucose-dependent insulin expression using EBV-based episomal vector. The similarities between K-cells and pancreatic beta cells support that K-cells may make effective and ideal targeting cells for insulin gene therapy or alternative cell therapy.

Citations

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Relationship of traditional and nontraditional cardiovascular risk factors to coronary artery calcium in type 2 diabetes
Ju-Yeon Sim, Ju-Hee Kim, Yu-Bae Ahn, Ki-Ho Song, Je-Ho Han, Bong-Yun Cha, Sook-Kyung Lee, Sung-Dae Moon
Korean Diabetes Journal.2009; 33(6): 466. CrossRef
Transdifferentiation of Enteroendocrine K-cells into Insulin-expressing Cells
Esder Lee, Jun Mo Yu, Min Kyung Lee, Gyeong Ryul Ryu, Seung-Hyun Ko, Yu-Bae Ahn, Sung-Dae Moon, Ki-Ho Song
Korean Diabetes Journal.2009; 33(6): 475. CrossRef

Insulin Gene Therapy Using HVJ-liposome and Epstein-Barr Virus Plasmid in Murine Streptozotocin Induced Diabetes.: Yong Deuk Kim, Keun Gyu Park, Seong Wook Han, Jong Doek Ahn, Hyo Jung Lee, Mi Jung Kim, Hye Soon Kim, Nam Hee Park, In Kyu Lee; Korean Diabetes J. 2003;27(5):405-413. Published online October 1, 2003

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Abstract PDF: BACKGROUND
Despite improvement in insulin preparation and delivery, the use of insulin therapy alone to maintain normal glucose concentration and prevent the development of diabetic complication is not easy. Therefore, there has been considerable interest in developing gene therapy to supply insulin. We investigated that the administration of hemagglutinating virus of Japan (HVJ)- liposome complex, containing human insulin construct into the portal vein to control the blood glucose level in murine streptozotocin (STZ)-induced diabetes. METHODS: Human insulin gene was delivered to STZ-induced diabetic rats through the portal vein using HVJ-liposome containing Epstein-Barr virus (EBV) replicon-based plasmid (pEB). Blood glucose and body weight were measured after insulin gene delivery. The animals were sacrificed 28 days later and the livers were collected for immuno-histochemical staining of insulin. In addition plasma insulin and C-peptide levels were measured. RESULTS: Significant decrease in blood glucose levels and an increase in insulin and C-peptide levels were observed in the insulin gene transfection group as compared to the control group. Immunohistochemical staining of insulin also showed significant differences between these two groups. CONCLUSION: This study demonstrated the possibility of insulin gene therapy through the portal vein using pEB and HVJ-liposome method to produce a sustained improvement of diabetic glucose metabolism.

Effect of Gi-proteins on Insulin Binding, Internalization and Recycling of Insulin Receptor in Bovine Aorta Endothelial Cell.: Hyuk Ho Kwon, Hyun Shik Son, Jung Min Lee, Seung Hyun Ko, Ok Ki Hong, Sung Dae Moon, Sang Ah Chang, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2003;27(1):26-38. Published online February 1, 2003

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Abstract PDF: BACKGROUND
Guanine nucleotide binding proteins (G-proteins) play important roles in the hormonal actions of many signal transduction systems. Possible roles for the Gi-protein in insulin action have been suggested. It is reported that Gi-protein is associated with insulin actions to a greater extent than Gs-protein. There are at least three different subtypes of Gi-proteins (Gi(alpha1), Gi(alpha2), and Gi(alpha3)), however, it is not certain which subtypes are associated with insulin receptors and their action. METHODS: To investigate the effects of Gi-proteins on insulin action, the Gi-proteins were overexpressed in cultured bovine aortic endothelial cells (BAEC), using the DNA-polylysine-adenovirus complex transfection method. After incubating for 24 hours, the BAEC were treated with 200 ng/mL insulin to evaluate the insulin binding, receptor internalization and recycling. RESULTS: The following results were found : 1) The binding of specific insulin bindings to the insulin receptors of endothelial cells were time-dependent, reaching their maximal levels in all cells after 30 minutes. The maximal specific bindings of the control, Gi(alpha1), Gi(alpha2), and Gi(alpha3) were 0.58+/-0.1, 0.54+/-0.08, 0.54+/-0.1, 0.53+/-0.09%, respectively. 2) The internalization of 125I-insulin, into endothelial cells, was assessed by the acid washing dissociation method, and occurred rapidly. There was a significant difference in the internalized radioactivity of the 125I-insulin in the overexpressed Gi(alpha2) protein group compared to the two groups. 3) The recycling of the insulin receptors in the three types of Gi-protein showed no significant difference between the three group. CONCLUSION: In conclusion, the Gi(alpha2) protein may be associated with internalization of the insulin-insulin receptor complex, and appears to be important in both the action of insulin and the intracellular processing of insulin receptors.

The Role of Akt-1/PKBalpha on Insulin Action in 3T3-L1 Adipocyte.: Jung Min Lee, Hyun Shik Son, Hyuk Sang Kwon, Seung Ki Kwack, Seung Hyun Ko, Sang Ah Chang, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Prem Sharma; Korean Diabetes J. 2002;26(4):274-285. Published online August 1, 2002

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Abstract PDF: BACKGROUND
S: Akt/PKB as a serine/threonine kinase is stimulated by insulin and other growth factors. And insulin stimulates glucose uptake by promoting the translocation of glucose transporter 4 (GLUT4) to the cell membrane. But, it is not clear that Akt/PKB, a downstream target of PI 3-kinase, is involved in glucose uptake pathway. In this study, we investigated the role of Akt/PKB, especially Akt-1, on insulin action in 3T3-L1 adipocyte. METHODS: We made recombinant Ad5.Akt-1 vector by the insertion of Akt-1 gene to adenoviral vector. And then, we overexpressed Akt-1 proteins(wild type and kinase inactive type) in 3T3-L1 adipocytes by using a adenoviral transfection method. We observed the changes of glucose uptake, glycogen synthesis, activities of mitogen-activated protein kinase (MAPK, also called extracellular signal-regulated kinase), p70 ribosomal s6 protein kinase (p70s6k), and glycogen synthase kinase 3 (GSK3) according to Akt-1 activity and insulin treatment. RESULTS: First, overexpression of Akt-1 did not affect to glucose uptake, whether insulin stimulates or not. Second, overexpression of Akt-1 did not affect the phosphorylation of p44/42-MAPK, either. Third, the glycogen synthesis was increased by overexpression of Akt-1. CONCLUSION: Akt-1 activation is necessary for glycogen synthesis, but is not essential for glucose transport in 3T3-L1 adipocytes.

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