Efficacy of insulin targeted gene therapy for type 1 diabetes mellitus: A systematic review and meta-analysis of rodent studies

Document Type: Review Article

Authors

1 Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Food Security Research Center, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran

3 The Early Life Research Unit, Division of Child Health, Obstetrics and Gynaecology, and Nottingham Digestive Disease Centre and Biomedical Research Centre, School of Medicine, University of Nottingham, Nottingham, UK

4 Department of Genetics & Maternal-Fetal Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

5 Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

6 3 The Early Life Research Unit, Division of Child Health, Obstetrics and Gynaecology, and Nottingham Digestive Disease Centre and Biomedical Research Centre, School of Medicine, University of Nottingham, Nottingham, UK

7 Gerfa Namayesh Azmayesh (GENAZMA) Science and Research Institute, Isfahan, Iran

Abstract

Objective(s): Diabetes mellitus (DM) is a major worldwide public health challenge, for which gene therapy offers a potential therapeutic approach. To date, no systematic review or meta-analysis has been published in this area, so we examined all relevant published studies on rodents to elucidate the overall effects of gene therapy on bodyweight, intraperitoneal glucose tolerance test (IPGTT), fasting blood glucose, and insulin in animals with type 1 DM.
Materials and Methods: The Cochrane Library, PubMed, Embase, ISI Web of Science, SCOPUS, and Google Scholar were systematically searched for potentially relevant studies. Mean±standard deviation (SD) was pooled using a random-effects model.
Results: After the primary search, out of 528 studies identified, 16 studies were in concordance with predefined criteria and selected for the final assessment. Of these, 12 studies used viral manipulation, and 4 employed non-viral vectors for gene delivery. The meta-analysis showed gene therapy with a viral vector decreased mean IPGTT (-12.69 mmol/l, P<0.001), fasting blood glucose (-13.51 mmol/l, P<0.001), insulin (398.28 pmol/l, P<0.001), and bodyweight (24.22 g, P<0.001), whereas non-viral vectors reduced fasting glucose (-29.95 mmol/l, P<0.001) and elevated insulin (114.92 pmol/l, P<0.001).
Conclusion: Gene therapy has favorable effects on alleviating type 1 DM related factors in diabetic rodents.

Keywords


1. World Health Organization. Global report on diabetes: World Health Organization; 2016.
2. Beladi-Mousavi SS, Bashardoust B, Nasri H, Ahmadi A, Tolou-Ghamari Z, Hajian S, et al. The theme of the world diabetes day 2014; healthy living and diabetes; a nephrology viewpoint. J Nephropharmacol. 2014;3:43.
3. Katsarou A, Gudbjörnsdottir S, Rawshani A, Dabelea D, Bonifacio E, Anderson BJ, et al. Type 1 diabetes mellitus. Nat Rev Dis Primers. 2017;3:1-17.
4. Yoon J-W, Jun H-S. Autoimmune destruction of pancreatic β cells. Am. J. Ther. 2005;12:580-91.
5. Guo S. Decoding insulin resistance and metabolic syndrome for promising therapeutic intervention. J Endocrinol 2014;220:E1-3.
6. Nathan DM. Diabetes: advances in diagnosis and treatment. Jama 2015;314:1052-62.
7. American Diabetes Association. Economic Costs of Diabetes in the U.S. in 2012. Available in Diabetes Care. 2013;36:1033-1046.
8. Miraghajani MS, Esmaillzadeh A, Najafabadi MM, Mirlohi M, Azadbakht L. Soy milk consumption, inflammation, coagulation, and oxidative stress among type 2 diabetic patients with nephropathy. Diabetes Care. 2012;35:1981-1985.
9. Miraghajani MS, Najafabadi MM, Surkan PJ, Esmaillzadeh A, Mirlohi M, Azadbakht L. Soy milk consumption and blood pressure among type 2 diabetic patients with nephropathy. J Ren Nutr. 2013;23:277-282.
10. Miraghajani M, Zaghian N, Mirlohi M, Feizi A, Ghiasvand R. The Impact of Probiotic Soy Milk Consumption on Oxidative Stress Among Type 2 Diabetic Kidney Disease Patients: A Randomized Controlled Clinical Trial. J Ren Nutr 2017;27:317-324.
11. Miraghajani M, Zaghian N, Mirlohi M, Ghiasvand R. Probiotic Soy Milk Consumption and Renal Function Among Type 2 Diabetic Patients with Nephropathy: a Randomized Controlled Clinical Trial. Probiotics Antimicrob Proteins. 2017:1-9.
12. Kareem N, Nazar CMJ, Mahmud SN, Ahmed A, Akhtar MH. Diabetes services and care provision. J Nephropharmacol. 2017;6:17.
13. Motedayen M, Sarokhani D, Meysami A, Jouybari L, Sanagoo A, Hasanpour Dehkordi A. The prevalence of hypertension in diabetic patients in Iran; a systematic review and meta-analysis. J Nephropharmacol. 2018;7:137-44.
14. The Diabetes Control and Complications Trial Research Group Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl j Med. 1993;1993:977-986.
15. Nasri H. Ameliorative impact of mycophenolate mofetil on diabetic kidney disease; a review on current knowledge. Immunopathol Persa. 2018;4:e19.
16. Mahmoodnia L, Aghadavod E, Beigrezaei S, Rafieian-Kopaei M. An update on diabetic kidney disease, oxidative stress and antioxidant agents. J Renal Inj Prev. 2017;6:153.
17. Fowler MJ. Microvascular and Macrovascular Complications of Diabetes. CliniCal Diabetes. 2008;26: 77-82.
18. Xu R, Li H, Lai-yin T, Hsiang-fu K, Lu H, Lam K. Diabetes gene therapy: potential and challenges. Curr Gene Ther. 2003;3:65-82.
19. Hosseini SM, Amini M, Roosta S, Beigrezaei S. Trends of serum creatinine among patients with type 2 diabetes in Isfahan endocrine and metabolism research center; a longitudinal study. J Prev Epidemiol. 2016;2: e01.
20. Shrestha N, Araújo F, Sarmento B, Hirvonen J, Santos HA. Gene-based therapy for Type 1 diabetes mellitus: viral and nonviral vectors. Diabetes Management. 2014;4:367.
21. Ren B, O’brien BA, Byrne MR, Ch’ng E, Gatt PN, Swan MA, et al. Long‐term reversal of diabetes in non‐obese diabetic mice by liver‐directed gene therapy. J Gene Med.. 2013;15:28-41.
22. Elsner M, Terbish T, Jörns A, Naujok O, Wedekind D, Hedrich H-J, et al. Reversal of diabetes through gene therapy of diabetic rats by hepatic insulin expression via lentiviral transduction. Mol ther. 2012;20:918-926.
23. Olson DE, Paveglio SA, Huey PU, Porter MH, Thulé PM. Glucose-responsive hepatic insulin gene therapy of spontaneously diabetic BB/Wor rats. Hum gene ther. 2003;14:1401-1413.
24. Rasouli M NAZ, R Omar A, Ahmad Z. Insulin secreted from genetically engineered intestinal cells reduces blood glucose levels in diabetic mice. Curr gene ther. 2013;13:229-239
25. Niu L, DAI Z. Expression of human insulin gene wrapped with chitosan nanoparticles in NIH3T3 cells and diabetic rats. Acta Pharmacol Sin. 2008;29:1342-1349
26. Niu L, Xu Y-C, Dai Z, Tang H-Q. Gene therapy for type 1 diabetes mellitus in rats by gastrointestinal administration of chitosan nanoparticles containing human insulin gene. World j gastroenterol. 2008;14:4209.
27. Cheung AT, Dayanandan B, Lewis JT, Korbutt GS, Rajotte RV, Bryer-Ash M, et al. Glucose-dependent insulin release from genetically engineered K cells. Science. 2000;290:1959-1962.
28. Thulé PM, Campbell AG, Jia D, Lin Y, You S, Paveglio S, et al. Long term glycemic control with hepatic insulin gene therapy in streptozotocin‐diabetic mice. j gene med. 2015;17:141-152.
29. Ren B, O’Brien B, Swan M, Koina M, Nassif N, Wei M, et al. Long-term correction of diabetes in rats after lentiviral hepatic insulin gene therapy. Diabetologia. 2007;50:1910-1920.
30. Hsu PY-J, Kotin RM, Yang Y-W. Glucose-and metabolically regulated hepatic insulin gene therapy for diabetes. Pharm res. 2008;25:1460-1468.
31. Han J, McLane B, Kim E-H, Yoon J-W, Jun H-S. Remission of diabetes by insulin gene therapy using a hepatocyte-specific and glucose-responsive synthetic promoter. Mol ther. 2011;19:470-478.
32. Kolodka TM, Finegold M, Moss L, Woo S. Gene therapy for diabetes mellitus in rats by hepatic expression of insulin. Proc Nati Acad Sci. 1995;92:3293-3297.
33. Elsner M, Jörns A, Lenzen S. Diabetes therapy by lentiviral hepatic insulin gene expression without transformation of liver. Diabetologia. 2008;51:694-695.
34. Oh TK, Li MZ, Kim ST. Gene therapy for diabetes mellitus in rats by intramuscular injection of lentivirus containing insulin gene. Diabetes res clin pract. 2006;71:233-240.
35. Oded Singer FG, Jerry Olefsky, Inder M. Verma. Gene Therapy for Diabetes Using Lentiviral Vectors. Mol Ther 2002;5:S340.
36. Corbella P, Perani L, Mingozzi F, Recchia A, Mavilio F, Roncarolo M, et al. Insulin-gene therapy of diabetes in mice by glucose-regulated helper-dependent adenoviral vectors. Mol ther. 2003;7:79-80.
37. Atkinson MA, Eisenbarth GS. Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet. 2001;358:221-229.
38. Aghadavoud E, Nasri H, Amiri M. Molecular signaling pathways of diabetic kidney disease; new concepts. J Prev Epidemiol. 2017;2:e03
39. Ghaderian SB, Beladi-Mousavi SS. The role of diabetes mellitus and hypertension in chronic kidney disease. J renal inj prev. 2014;3:109-110.
40. Gheith O, Farouk N, Nampoory N, Halim MA, Al-Otaibi T. Diabetic kidney disease: world wide difference of prevalence and risk factors. J nephropharmacol. 2016;5:49-56.
41. Stern MP, Haffner SM. Body fat distribution and hyperinsulinemia as risk factors for diabetes and cardiovascular disease. Arteriosclerosis. 1986;6:123-30.
42. Velayuthan MR, Elumalai R, Periyasamy S, Lakkakula BV. Insulin receptor gene polymorphisms modify the progression of kidney failure in diabetic nephropathy patients. J Prev Epidemiol. 2017;2:e06.
43. Palizban A, Salehi R, Nori N, Galehdari H. In vivo transfection rat small intestine K-cell with pGIP/Ins plasmid by DOTAP liposome. J drug target. 2007;15:351-357.
44. Momenzadeh S, Sadeghi A, Vatandoust N, Salehi R. Evaluation of In Vivo Transfection Efficiency of Eudragit Coated Nano-particles of Chitosan-DNA: A pH-sensitive System Prepared for Oral DNA Delivery. Iran Red Crescent Med J. 2015;17: e16761.
45. Handorf AM, Sollinger HW, Alam T. Insulin gene therapy for type 1 diabetes mellitus. Exp clin transplant. 2015;13:37-45.
46. Yeung C-M, Wong CK, Chung SK, Chung SS, Chow BK. Glucose-dependent insulinotropic polypeptide gene expression in the stomach: revealed by a transgenic mouse study, in situ hybridization and immunohistochemical staining. Mol cell endocrinol. 1999;154:161-170.
47. Cho YM, Kieffer TJ. 4 K-cells and Glucose-Dependent Insulinotropic Polypeptide in Health and Disease. Vitam horm. 2010;84:111.