Abstract
Type 2 diabetes mellitus is a chronic metabolic disease characterized by resistance to peripheral insulin actions. Mesenchymal stem cells have been studied for years in T2DM therapy, including adipose tissue-derived mesenchymal stem cells (AD-MSCs). Orexin neuropeptides (A and B) are well-known regulators of appetite and physical activity. The aim of this work was to elucidate the possible therapeutic effect of AD-MSC preconditioning with orexin A (OXA) on insulin resistance in rats. Twenty-eight adult male albino rats were divided into 4 equal groups: a normal control group and 3 diabetic groups (a control T2DM group, diabetic rats treated by an AD-MSCs group, and diabetic rats treated by AD-MSCs preconditioned with OXA). We noticed that the treated groups showed a significant alleviation of insulin resistance parameters as shown in lowering the serum levels of glucose, insulin, total cholesterol, inflammatory markers, and HOMA-IR as compared to the control diabetic group with more significant reduction observed in the OXA-pretreated AD-MSCs-administrated group. More improvement was also noted in the glucose uptake and GLUT-4 gene expression in the skeletal muscle and adipose tissue in the OXA-pretreated AD-MSCs-administrated group compared to the untreated diabetic group. Conclusion. Preconditioning of AD-MSCs with OXA can significantly increase their potential to reduce the insulin resistance in the rat model of T2DM.
Highlights
Diabetes mellitus is a common public health problem worldwide, with extensive medical, economic, and social consequences
The schematic figure illustrating the timeline of the experimental protocol is shown in Figure 1: group I, normal control group; group II, diabetic control T2DM rats with no treatment given; group III, T2DM rats received four infusions of adipose tissue-derived mesenchymal stem cells (AD-Mesenchymal stem cells (MSCs)); and group IV, T2DM rats received AD-MSCs pretreated with orexin A (OXA)
We found that AKT2 mRNA gene expression was significantly decreased in both muscle and adipose tissue in the control diabetic rats compared to the normal control group (p < 0:05)
Summary
Diabetes mellitus is a common public health problem worldwide, with extensive medical, economic, and social consequences. Type 2 diabetes (T2D) is known as the adult-onset or non-insulin-dependent diabetes (NIDDM). It accounts for over 90% of all diabetics [1]. Obesity is the most common risk factor for the development of T2D. The link between insulin resistance (IR) and T2D was confirmed for a long time. T2D is a complex metabolic disorder characterized by alterations in lipid metabolism, hyperglycemia, basal hyperinsulinemia, insulin resistance, and pancreatic β-cell dysfunction [2]
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