Patients with diabetes mellitus type1 (DM1) have a relative insulin deficiency with elevated triacylglycerides (TAG) production. Adipokines are important in fat distribution, inflammation, and endothelial function. Dapagliflozin (Dapa) and pioglitazone (Pio) are oral hypoglycemic drugs for the treatment of DM2. They have also pleiotropic effects on lipid profile and body weight. The effect of these drugs on lipoproteins and adipokines levels in DM1 is poorly understood.
Design and method:
DM1 in male Wistar rats was induced by a single dose of streptozotocin (STZ). Animals were then divided into five groups: Controls, diabetic animals (DM), DM treated with Dapa, DM treated with Pio, DM treated with combination DapaPio. Therapies were mixed in rat chow. Control and DM groups received standard chow. After 6 weeks of treatment serum glucose and lipid levels were determined. Visceral adipose tissue (VAT) gene expression of leptin (Lep), adiponectin (AdipoQ), hormone-sensitive lipase (HSL), lipoprotein lipase (LPL), tumor necrosis factor-alpha (TNFa) and interleukin 6 (IL6) were measured by RT qPCR and their levels in plasma were determined by ELISA method.
STZ injection led to a significant increase in both fasting and postprandial glucose levels and all levels of lipoproteins except high-density lipoproteins (HDL), which were decreased. We also found decreased levels of Lep, AdipoQ, LPL, and IL6, and increased HSL and TNFa in plasma in DM group. These results were supported by the same significant changes in gene expression in VAT. A combination of DapaPio resulted in a significant decrease in serum levels of both glucose levels. Pio and DapaPio administration decreased TAG and total cholesterol and increased HDL. Lep, AdipoQ, LPL and IL6 plasma levels were increased, and HSL, TNFa were decreased after administration of Dapa, Pio and their combination. Both monotherapy and combination significantly modulated Lep, TNFa and IL6 gene expression in VAT.
DM1 in rats influenced not only glucose levels but also lipoproteins and adipokines in plasma, which could be affected by Dapa, Pio and DapaPio. Therapy can also change the gene expression of Lep, AdipoQ, TNFa, and IL6 in adipose tissue in rats with DM1.