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Metformin Modulates GLP-1- and GIP-Mediated Intracellular Signaling under Normoglycemic Conditions

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DOI: 10.4236/ojemd.2013.37036    3,031 Downloads   5,622 Views   Citations

ABSTRACT

GLP-1 and GIP promote insulin secretion from pancreatic β-cells by inducing intracellular signals such as Ca2+ and cAMP. Metformin primarily acts by inhibiting glucogenesis in the liver and promoting glucose metabolism in the muscle. It is used as a concomitant drug with the incretin in the treatment of T2D. We focused on intracellular signals under various glucose concentrations and assessed the effects of metformin on incretin signaling in MIN6 β-cells. Metformin inhibited incretin-induced [Ca2+]i in the presence of 5.5 mM glucose but not 16.7 mM glucose. In accordance with low [Ca2+]i, insulin secretion from MIN6 cells declined, despite enhanced incretin-induced cAMP production. Abundant expressions of Adcy 6 and 9, which are negatively controlled by Ca2+ signals, were detected in MIN6 cells. Thus, increasing cAMP production was associated with the inhibition of Ca2+ mobilization by metformin. However, we show that metformin controls insulin secretion by inhibiting incretin-mediated [Ca2+]i under normoglycemic conditions.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

K. Shinmura, T. Negoro, S. Shimizu, G. Roncador, T. Hirano and Y. Nakano, "Metformin Modulates GLP-1- and GIP-Mediated Intracellular Signaling under Normoglycemic Conditions," Open Journal of Endocrine and Metabolic Diseases, Vol. 3 No. 7, 2013, pp. 263-270. doi: 10.4236/ojemd.2013.37036.

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