Elegant studies from Wang and colleagues demonstrate that insulin induces activation of GABA(A) receptors in the alpha cells by GABA receptor translocation via an Akt kinase-dependent pathway. This leads to membrane hyperpolarization in the alpha cells and, ultimately, suppression of glucagon secretion. Hence, insulin may directly inhibit glucagon secretion, and indirectly potentiate the inhibitory effects of GABA concomitant released by β -cells-See Intra-islet insulin suppresses glucagon release via GABA-GABA(A) receptor system. Cell Metab. 2006 Jan;3(1):47-58
Global control of gluconeogenesis is mediated by glucagon ( released when blood glucose is low ); it triggers phosphorylation of enzymes and regulatory proteins by Protein Kinase A (a cyclic AMP regulated kinase) resulting in inhibition of glycolysis and stimulation of gluconeogenesis. Recent studies have shown that the absence of hepatic glucose production has no major effect on the control of fasting plasma glucose concentration. Compensatory induction of gluconeogenesis occurs in the kidneys and intestine, driven by glucagon , glucocorticoids , and acidosis.