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Glucose stimulated insulin secretion: Effect of chronic acidosis and alkalosis in MIN6 cells
Author(s) -
Gu Xiang Q,
Ryu Julie,
Sun Xiaolu,
Yao Hang,
Gavrialov Orit,
LuBo Ying,
Cirulli Vincenzo,
Haddad Gabriel G.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1035.9
Subject(s) - extracellular , medicine , alkalosis , endocrinology , acidosis , chemistry , intracellular ph , insulin , rheobase , secretagogue , electrophysiology , biochemistry , biology
In addition to exacerbating insulin resistance, obesity has been associated with obstructive sleep apnea and hypercapnia. To explore the underlying mechanisms of these latter phenomena on glucose‐stimulated insulin secretion, we explored the effect of CO 2 /HCO 3 − /pH alterations in mouse secretagogue‐responsive insulinoma cells MIN6 exposed to different extracellular pHs ([pH] o ) for 6 days, and measured glucose‐stimulated insulin secretion (GSIS), and passive and active electrophysiological membrane properties. We found that 1) when the extracellular [pH] o was alkaline (7.9) (fixing CO 2 concentration at 5% and increasing NaHCO 3 concentrations from 18 to 50 mM) GSIS decreased significantly and this was accompanied by a significantly hyperpolarized V m , decreased R i and increase in rheobase; 2) by fixing NaHCO 3 at 18 mM and increasing the CO 2 concentration from 5% to 15%, there was no effect on GSIS, resting membrane potential (V m ), and input resistance (R i ); 3) a decrease in extracellular pH (a pH of 6.5 or below with 5% CO 2 and 0 mM NaHCO 3 ) inhibited GSIS, and this was accompanied by a significantly depolarized V m , decreased R i and increase in rheobase. We conclude that 1) although GSIS does not depend on extracellular pH when extracellular pH is between 7.1 and 7.7, GSIS decreased when pH was outside this range; 2) uncompensated extracellular pH by eliminating NaHCO 3 reduces GSIS, and this may involve a chloride‐dependent mechanism. These findings have important implications for the management of insulin resistance and diabetes in obese patients.