Conditional, tissue-specific expression of Q205L G alpha i2 in vivo mimics insulin action.
Deficiency of the G protein subunit G alpha i2 that is known to mediate the inhibitory control of adenylylcyclase impairs insulin action [11]. Using the promoter for the phosphoenolpyruvate carboxykinase gene, conditional tissue-specific expression of the constitutively active mutant form (Q205L) of G alpha i2 was achieved in mice harboring the transgene. Expression of Q205L G alpha i2 was detected in liver and adipose tissue of transgenic mice. Whereas the G alpha i2 deficient mice displayed blunted glucose tolerance, the Q205L G alpha i2 expressing mice displayed enhanced glucose tolerance. Hexose transport and the recruitment of GLUT4, but not GLUT1, transporters to the membrane were elevated in adipocytes from Q205L G alpha i2 expressing mice in the absence of insulin. Additionally, hepatic glycogen synthase was found to be activated in Q205L G alpha i2 expressing mice, in the absence of the administration of insulin. Serum insulin levels in transgenic mice fasted overnight were equivalent to those of their control littermates. These data demonstrate that much as G alpha i2 deficiency leads to insulin resistance, expression of Q205L constitutively active G alpha i2 mimics insulin action in vivo, reflecting a permissive role of G alpha i2 in signaling via this growth factor receptor tyrosine kinase linked pathway.
Chen
J F
JF
Department of Pharmacological Sciences, School of Medicine-HSC, SUNY, Stony Brook 11794-8651, USA.
Guo
J H
JH
Moxham
C M
CM
Wang
H Y
HY
Malbon
C C
CC
D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D006528:Carcinoma, Hepatocellular; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019204:GTP-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4; D006006:Glycogen Synthase / Q000378:metabolism; D006601:Hexoses / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D008099:Liver / Q000737:chemistry / Q000201:enzymology; D008113:Liver Neoplasms; D051379:Mice; D008822:Mice, Transgenic; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D009154:Mutation; D009928:Organ Specificity; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051381:Rats; D014407:Tumor Cells, Cultured
D051275:Glucose Transporter Type 4; D006601:Hexoses; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D011518:Proto-Oncogene Proteins; C495693:Slc2a4 protein, mouse; C495694:Slc2a4 protein, rat; D006006:Glycogen Synthase; D019204:GTP-Binding Proteins; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C498016:Gnai2 protein, mouse; C498017:Gnai2 protein, rat; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D005947:Glucose