143-LB: Calorie Restriction in Combination with GABA Ameliorates Type 2 Diabetes

Abstract

Dysfunction of adipocytes and β-cells are crucial in the progression of obesity-related insulin resistance and type 2 diabetes (T2D). γ-Aminobutyric Acid (GABA) is a key neurotransmitter and is secreted by β-cells. It exerts protective and regenerative effects on β-cells. At the metabolic level, Calorie Restriction (CR) has been shown to improve insulin sensitivity, reduces Fasting Blood Glucose (FBG) and increases insulin levels. GABA and CR are speculated to show an additive effect on insulin secretion and β-cell regeneration via GABA signaling and enhance insulin sensitivity ameliorating T2D manifestations. We have evaluated the effect of GABA and CR combination on β-cell regeneration and insulin sensitivity in High Fat Diet (HFD) and streptozotocin (STZ) induced late stage T2D mouse model. Our results show favorable changes in the measured parameters. GABA+CR group showed reduced FBG levels and improved whole-body insulin responsiveness indicated by increased insulin levels, insulin sensitivity, and glucose tolerance. The combination therapy improved the lipid profile by significantly reducing triglycerides, total cholesterol, and LDL levels and increased HDL levels. The transcript expression profile of metabolic enzymes in the liver indicates a significant decrease in gluconeogenesis and glycogenolysis. The transcript levels indicate decreased lipolysis and increased fatty acid synthesis in the adipose tissue. The transcript levels of mitochondrial biogenesis in the skeletal muscle indicate increased effect of combination therapy, thereby promoting insulin sensitivity. Also, combination therapy promoted β-cell proliferation.

In conclusion, calorie restriction in combination with GABA ameliorates T2D in the mouse model by inducing β-cell regeneration mediated by GABA and increased insulin sensitivity by CR diet.