Expression of constitutively activated Gialpha2 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 Gialpha2 in vivo ameliorates streptozotocin-induced insulin-dependent diabetes mellitus in transgenic mice. Conditional expression of Q205L Gialpha2 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.
Zheng
X L
XL
Department of Molecular Pharmacology, Diabetes and Metabolic Diseases Research Program, University Medical Center, SUNY/Stony Brook, Stony Brook, New York 11794-8651, USA.
Guo
J
J
Wang
H y
Hy
Malbon
C C
CC
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000517:prevention & control; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000517:prevention & control; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000096:biosynthesis / Q000235:genetics*; D005951:Glucose Tolerance Test; D006006:Glycogen Synthase / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism; D017354:Point Mutation; D051381:Rats
D001786:Blood Glucose; D006006:Glycogen Synthase; D019206:GTP-Binding Protein alpha Subunits, Gi-Go