Simultaneous Metformin and Sitagliptin Effect on Proteins Content Involved in Insulin Resistance in Human Adipose Tissue of Type 2 Diabetes: A Clinical Trial

  • Reza Didehdar Department of Biochemistry and Molecular Biology, Faculty of Medicine, International Campus of Shahid Saduoghi University of Medical Sciences, Yazd, Iran
  • Yousof Naghiaee Department of Biochemistry and Molecular Biology, Faculty of Medicine, Shahid Saduoghi University of Medical Sciences, Yazd, Iran
  • Javad Mohiti-Ardekani Department of Biochemistry and Molecular Biology, Faculty of Medicine, Shahid Saduoghi University of Medical Sciences, Yazd, Iran
  • Naeimeh Heiranizadeh Department of General Surgery, Faculty of Medicine, Shahid Saduoghi University of Medical Sciences, Yazd, Iran.
  • Masaoud Rahmanian Department of Internal Medicine, Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Keywords: Insulin Resistance, Metformin, Sitagliptin, Diabetes, Glucose transporter 4

Abstract

Objective: Obesity ultimately results in a variety of metabolic changes, the most significant of which is insulin resistance, which is a contributing factor to both type 2 diabetes and permanent insulin resistance? The purpose of this study was to determine whether these two medications break down insulin resistance concurrently and, if so, what modifications are made to the levels of the targeted proteins in the insulin signaling pathway in type 2 diabetic adipose tissue in humans.

Materials and Methods: A clinical trial is described in this article. We used (sodium dodecyl sulfate poly- acrylamide gel electrophoresis (SDSPAGE) and western blot analyses to identify the presence of insulin resistance-related proteins Insulin Receptor Substrate-1 (IRS-1), phosphatidylinositol 3 kinase (PI3K), and Mammalian Target of Rapamycin (mTOR) in the adipose tissue of type 2 diabetic patients. We looked at six individuals who were receiving simultaneous treatment with metformin and sitagliptin for three months, four of whom returned after treatment.

Results: Increases in glucose disposal, decreases in serum glucose levels (P< 0.05), decreased insulin resistance (P< 0.05), and changes in serum insulin levels were seen after concurrent therapy with metformin and sitagliptin. Conversely, an increase in the proteins implicated in insulin resistance, including PI3K, mTOR, and IRS-1, was noted in the adipose tissue of diabetic individuals (P< 0.05).

Conclusion: The insulin resistance-related proteins IRS-1, PI3K, and mTOR in type 2 diabetic adipose tissue were markedly improved by concurrent metformin and sitagliptin treatment.

Published
2025-07-28
Section
Articles