Triphenyltin impairs insulin secretion by decreasing glucose-induced NADP(H) and ATP production in hamster pancreatic β-cells

Oral administration of triphenyltin chloride (TPT) (6 mg/100 g body weight) inhibits insulin secretion by decreasing glucose-induced cytoplasmic Ca2+ concentration ([Ca2+]i) in pancreatic β-cells of the hamster. To test the possibility that the abnormal level of the [Ca2+]i induced by TPT administration could be due to a defect in the metabolic signal of glucose in the β-cells, we tested the effects of TPT administration on the glucose-induced NAD(P)H and ATP production, and on the changes of membrane potential and [Ca2+]i by glucose and high K+ in the β-cells. The [Ca2+]i was measured in islet cells loaded with fura-2. TPT administration significantly reduced the NAD(P)H and ATP production, the depolarization of plasma membrane, and insulin secretion by 15 mM glucose in islet cells. TPT administration also reduced the insulin secretion by 10 mM dihydroxyacetone and glyceraldehyde. However, TPT administration did not affect the increase of [Ca2+]i and the insulin secretion by 30 mM K+ or 100 μM tolbutamide, and the membrane potential by 30 mM K+, and the insulin secretion by 10 mM α-ketoisocaproic acid and 0.5 mM formycin A, an analog of ATP in the presence of 15 mM glucose. These results suggested that the pathogenesis of TPT-induced hyperglycemia in hamster involves the reduction of [Ca2+]i and insulin secretion in response to KATP channel-dependent depolarization, which is related to the decrease of NAD(P)H and ATP production in pancreatic islet cells after glucose metabolism.