Phosphate depletion reduces potassium-induced insulin secretion.
Potassium-induced insulin secretion is impaired in rats with chronic renal failure and a sustained rise in cytosolic calcium ([Ca2+]i). It has been found that the calcium signal (delta[Ca2+]i) and the delta [Ca2+]i/basal [Ca2+]i in these animals in response to potassium are smaller than those in normal rats and that these defects may underlie, at least in part, the reduced potassium-induced insulin secretion, since the latter depends on an appropriate rise in [Ca2+]i. Since phosphate depletion (PD) is another model associated with a rise in the basal level of [Ca2+]i of pancreatic islets, it provides another metabolic setting for investigating the interaction between high [Ca2+]i of islets and their response to potassium. We examined the potassium-induced insulin secretion, the potassium-induced calcium signal, and the delta [Ca2+]i/basal [Ca2+]i in islets of PD rats with and without elevated [Ca2+]i. The levels of the basal [Ca2+]i in the islets of PD rats were significantly (P less than 0.01) higher than those in pair-weighed (PW) animals and those in PD and PW rats treated with verapamil, which has been shown to prevent the rise in [Ca2+]i in islets of PD rats. Both initial and total insulin secretion, the calcium signal, and the delta [Ca2+]i/basal [Ca2+]i in the islets of PD rats were significantly (P less than 0.01) smaller than those in the other three groups of animals. There were no significant differences in basal levels of [Ca2+]i and in calcium signal, delta [Ca2+]i/basal [Ca2+]i, and insulin secretion among PW rats, verapamil-treated PD rats, and verapamil-treated PW rats. The results are consistent with the notion that elevated resting levels of [Ca2+]i interfere with the magnitude of the calcium signal and the ratio of calcium signal to basal [Ca2+]i, and these derangements, at least in part, underlie the impaired potassium-induced insulin secretion in PD.
Department of Medicine, University of Southern California School of Medicine, Los Angeles 90033.
G Z
GZ
Fadda
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P
Thanakitcharu
S G
SG
Massry
D000818:Animals; D002118:Calcium / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D010710:Phosphates / Q000502:physiology*; D010758:Phosphorus / Q000097:blood; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology
D007328:Insulin; D010710:Phosphates; D010758:Phosphorus; D014700:Verapamil; D011188:Potassium; D002118:Calcium