EXPRESSION OF CONSTITUTIVELY ACTIVATED G(I-ALPHA-2) IN-VIVO AMELIORATES STREPTOZOTOCIN-INDUCED DIABETES

Streptozotocin treatment in vivo generates a model of insulin-dependen t diabetes mellitus via destruction of the pancreatic beta-cells respo nsible 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 mel litus in transgenic mice. Conditional expression of Q205L G(i alpha 2) in vivo in liver, skeletal muscle, and adipose tissue markedly rectif ies glucose tolerance, fasting glucose levels, and glycogen synthase a ctivation in the mice with insulin-dependent diabetes mellitus, provid ing a novel therapeutic target for diabetes.