Oral administration of
triphenyltin chloride (
TPT) (6 mg/100g
body weight) inhibits insulin secretion by decreasing
glucose-induced cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) in pancreatic β-cells of the hamster. To test the possibility that the abnormal level of the [Ca(2+)](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 [Ca(2+)](i) by
glucose and high K(+) in the β-cells. The [Ca(2+)](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 10mM
dihydroxyacetone and
glyceraldehyde. However,
TPT administration did not affect the increase of [Ca(2+)](i) and the insulin secretion by 30 mMK(+) or 100 μM
tolbutamide, and the membrane potential by 30 mMK(+), and the insulin secretion by 10mM α-ketoisocaproic
acid and 0.5mM
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 [Ca(2+)](i) and insulin secretion in response to K(
ATP) channel-dependent depolarization, which is related to the decrease of
NAD(P)H and
ATP production in pancreatic islet cells after
glucose metabolism.