Recent studies have suggested that glucose may activate insulin gene transcription through increases in intracellular Ca2+ concentration, possibly acting via the release of stored insulin. We have investigated this question by dynamic photon-counting imaging of insulin- and c-fos-promoter-firefly luciferase reporter construct activity. Normalized to constitutive viral promoter activity, insulin promoter activity in MIN6 β-cells was increased 1.6-fold after incubation at 30 mM compared with 3 mM glucose, but was unaltered at either glucose concentration by the presence of insulin (100 nM) or the Ca2+ channel inhibitor, verapamil (100 μM). Increases in intracellular [Ca2+] achieved by plasma membrane depolarization with KCl failed to enhance either insulin or c-fos promoter activity in MIN6 cells, but increased c-fos promoter activity 5-fold in AtT20 cells. Together, these results demonstrate that glucose can exert a direct effect on insulin promoter activity in islet β-cells, via a signalling pathway which does not require increases in intracellular [Ca2+] nor insulin release and insulin receptor activation.
Glucose enhances insulin promoter activity in MIN6 β-cells independently of changes in intracellular Ca2+ concentration and insulin secretion
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Helen J. KENNEDY, Imran RAFIQ, Aristea E. POULI, Guy A. RUTTER; Glucose enhances insulin promoter activity in MIN6 β-cells independently of changes in intracellular Ca2+ concentration and insulin secretion. Biochem J 1 September 1999; 342 (2): 275–280. doi: https://doi.org/10.1042/bj3420275
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