Metformin Modulates GLP-1- and GIP-Mediated Intracellular Signaling under Normoglycemic ConditionsReportar como inadecuado




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GLP-1 and GIP promote insulin secretion frompancreatic β-cells by inducingintracellular signals such as Ca2+ and cAMP. Metformin primarilyacts by inhibiting glucogenesis in the liver and promoting glucose metabolismin the muscle. It is used as a concomitant drug with the incretin in thetreatment of T2D. We focused on intracellular signals under various glucoseconcentrations and assessed the effects of metformin on incretin signaling inMIN6 β-cells. Metformin inhibited incretin-induced Ca2+i in the presence of 5.5 mM glucose but not 16.7 mM glucose. In accordance withlow Ca2+i, insulin secretion from MIN6 cells declined,despite enhanced incretin-induced cAMP production. Abundant expressions of Adcy 6 and 9, which are negativelycontrolled by Ca2+ signals, were detected in MIN6 cells. Thus, increasingcAMP production was associated with the inhibition of Ca2+ mobilization by metformin. However, we show that metformin controls insulinsecretion by inhibiting incretin-mediated Ca2+i undernormoglycemic conditions.



KEYWORDS

Metformin; GLP-1; GIP; Calcium; cAMP; Insulin Secretion

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.





Autor: Kyoko Shinmura, Takaharu Negoro, Shunichi Shimizu, Giovanna Roncador, Tsutomu Hirano, Yasuko Nakano

Fuente: http://www.scirp.org/



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