Repurposing Pitavastatin and L-Glutamine: Replenishing -Cells in Hyperlipidemic Type 2 Diabetes Mouse Model

Type 2 diabetes (T2D) is associated with obesity and declining beta-cells. L-glutamine has been implicated in the amelioration of T2D by virtue of its incretin secretagogue property while, there are mixed reports on pitavastatin's adiponectin potentiating ability. We aimed to investigate the effect of pitavastatin (P), L-glutamine (LG), and combination (P + LG) on glycemic control and beta-cell regeneration in a high-fat diet (HFD) + streptozotocin (STZ)-induced T2D mouse model. C57BL6/J mice treated with HFD + STZ were divided into four groups: diabetes control (HFD + STZ), P, LG, and P + LG, while the control group (NCD) was fed with the normal-chow diet. Significant amelioration was observed in the combination therapy as compared to monotherapies in respect of (i) insulin resistance, glucose intolerance, lipid profile, adiponectin levels, and mitochondrial complexes I, II, and III activities, (ii) reduced phosphoenolpyruvate carboxykinase, glucose 6-phophatase, glycogen phosphorylase, and GLUT2 transcript levels with increased glycogen content in the liver, (iii) restoration of insulin receptor 1 beta, pAkt/Akt, and AdipoR1 protein levels in skeletal muscle, and (iv) significant increase in islet number due to beta-cell regeneration and reduced beta-cell death. L-glutamine and pitavastatin in combination can ameliorate T2D by inducing beta-cell regeneration and regulating glucose homeostasis.