Modulation of GLUT4 and FOXO1 Expression by SH-MSC and Alkaline Water in Experimental Type 2 Diabetes Mellitus

Dian Fatmawati; Agung  Putra; Eko  Setiawan

doi:10.56303/jhnresearch.v4i3.562

Authors

Dian Fatmawati Postgraduate Student of the Biomedical Sciences Department, Universitas Islam Sultan Agung, Indonesia
Agung Putra Department of Postgraduate Biomedical Science, Universitas Islam Sultan Agung, Indonesia
Eko Setiawan Department of Postgraduate Biomedical Science, Universitas Islam Sultan Agung, Indonesia

Keywords:

alkaline water, FOX01, GLUT4, SH-MSC, Type 2 Diabetes Mellitus

Abstract

Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder characterized by insulin resistance, which is associated with the dysregulation of glucose transporter 4 (GLUT4) and forkhead box protein O1 (FOXO1). The secretome from hypoxia-preconditioned mesenchymal stem cells (SH-MSC) and alkaline water have been proposed as potential therapies to modulate these molecular targets and improve glycemic control; however, their combined effects remain unexplored. Using an experimental post-test-only control group design, this study aimed to assess the possible additive effect of SH-MSC and alkaline water on the expression of GLUT4 and FOXO1 in Wistar rats with type 2 diabetes. Twenty-five male Wistar rats were split into five groups: healthy control (G1), T2DM control (G2), T2DM with metformin (G3), T2DM with SH-MSC (G4), and T2DM with SH-MSC and alkaline water (G5). Streptozotocin and nicotinamide were utilized to induce T2DM, and qRT-PCR was used to measure the expression of GLUT4 and FOXO1 in pancreatic tissue. One-way ANOVA and a post hoc LSD test were used for statistical analysis. The findings recognized that while GLUT4 expression was decreased, T2DM induction markedly increased fasting blood glucose levels and FOXO1 expression. SH-MSC treatment significantly upregulated GLUT4 and downregulated FOXO1 equated to the control T2DM group, and while the addition of alkaline water showed a further trend of improvement, this difference was not statistically significant. These findings suggest that SH-MSC therapy effectively improves glucose metabolism by modulating GLUT4 and FOXO1 expression, with the potential for alkaline water as an adjunctive therapy in T2DM management

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