Key words Gαi2
Springer Online Journal Archives 1860-2000
Abstract Deficiency of the G protein subunit Gαi2 that is known to mediate the inhibitory control of adenylylcyclase impairs insulin action . Using the promoter for the phosphoenolpyruvate carboxykinase gene, conditional, tissue-specific expression of the constitutively active mutant form (Q205L) of Gαi2 was achieved in mice harboring the transgene. Expression of Q205L Gαi2 was detected in liver and adipose tissue of transgenic mice. Whereas the Gαi2 deficient mice displayed blunted glucose tolerance, the Q205L Gαi2 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 Gαi2 expressing mice in the absence of insulin. Additionally, hepatic glycogen synthase was found to be activated in Q205L Gαi2 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 Gαi2 deficiency leads to insulin resistance, expression of Q205L constitutively active Gαi2 mimics insulin action in vivo, reflecting a permissive role of Gαi2 in signaling via this growth factor receptor tyrosine kinase linked pathway.
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