ABSTRACT Elevated level of basal insulin secretion is a characteristic of type 2 diabetes mellitus. The mechanism underlying the phenomenon is poorly understood. We found T-type Ca2+ channel window currents contributive to increased basal [Ca2+]i in β-cells. Rat islet cells incubated in 11.1 mM glucose were found to have up-regulated Cav3.1/3.2 mRNA and protein expression and elevated basal [Ca2+]i. The increase in basal [Ca2+]i was substantially decreased in the presence of NNC 55-0396 and siRNA targeting Cav3.1 and Cav3.2. High glucose exposure also contributed to elevated basal insulin secretion, which was reduced by chelating intracellular calcium or calcium antagonists. An in vivo study showed that T-type Ca2+ channel antagonists greatly reduced stable levels of insulin in a diabetic rodent model.
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