Targeting the Triumvirate in Type 2 Diabetes Mellitus

Background Diabetes mellitus remains a global health burden. The pathophysiology of type 2 diabetes (T2D) includes insulin resistance, oxidative stress, and inflammation. These mechanisms may underlie the development of diabetic kidney, non-alcoholic fatty liver, and cardiovascular diseases. Aim The aim of the present study was to explore the therapeutic effects of mesenchymal stem cells (MSCs) on the kidney, liver, and heart in a rat model of T2D. Methods Thirty male Wistar rats weighing 150-200 grams were divided equally into: 1-Control (C) group (received 5 consecutive intraperitoneal (i.p.) injections as well as a single intravenous (i.v.) injection of 0.9% saline), 2-Diabetes mellitus (DM) group (received 5 consecutive i.p. injections of streptozotocin (50 mg/kg), as well as a single i.v. injection of 0.9% saline 4 weeks after the induction of diabetes), 3-Diabetes mellitus treated with mesenchymal stem cells (DM+MSCs) group (received 5 consecutive i.p. injections of streptozotocin (50 mg/kg), as well as MSCs in a dose of 2 million cells per rat as an i.v. injection via rat tail vein 4 weeks after the induction of diabetes). At the end of the study, 24-hour urine and fasting blood samples were collected. The kidney, liver, heart, pancreas, and gastrocnemius muscle were removed and used for histopathological RT-PCR studies. Results Induction of diabetes mellitus resulted in significant deterioration in kidney, liver, and heart functions in the DM group when compared to the C group. Gene expression of GLUT4 was significantly decreased in the heart and gastrocnemius muscles in the DM group. Expression of mTOR was increased, while Nrf2 was decreased in the kidney, liver, heart, and pancreas in the DM group when compared to the C group. There was a significant improvement in the kidney, liver, and heart functions in the DM+MSCs group when compared to the DM group. Treatment with MSCs significantly restored the gene expression of GLUT4, mTOR, and Nrf2 when compared to the DM group but not to the C group. MSCs had anti-inflammatory and angiogenic capacities. Conclusion Cell-based therapeutic strategies can play a pivotal role in the complex pathophysiology of T2D. The treatment with MSCs significantly countered the deleterious effects on the kidney, liver, and heart in rat model of T2D. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.