Expression of constitutively activated Giα2 in vivo ameliorates Streptozotocin-induced diabetes

Streptozotocin treatment in vivo generates a model of insulin-dependent diabetes mellitus via destruction of the pancreatic beta-cells responsible for insulin secretion. Tissue-specific expression of the Q205L constitutively activated mutant form of the G-protein G(i alpha 2) in vivo ameliorates streptozotocin-induced insulin-dependent diabetes mellitus in transgenic mice. Conditional expression of Q205L G(i alpha 2) in vivo in liver, skeletal muscle, and adipose tissue markedly rectifies glucose tolerance, fasting glucose levels, and glycogen synthase activation in the mice with insulin-dependent diabetes mellitus, providing a novel therapeutic target for diabetes.