Temperature dependence of processes proximal and distal to the glucose-induced [Ca2+]i rise in stimulus-secretion coupling in rat pancreatic islets.
Cooling is known to inhibit glucose-induced insulin secretion from pancreatic islets, but temperature-dependent processes in stimulus-secretion coupling remain unclear. In the present study, we examined the effects of cooling on the glucose-induced increase in cytoplasmic Ca2+ concentration ([Ca2+]i) and concomitant insulin secretion in rat pancreatic islets to analyze the temperature dependence of processes proximal and distal to the Ca2+ signal in stimulus-secretion coupling. Rat pancreatic islets were isolated and perifused. [Ca2+]i was measured using fura-2. Glucose (15 mM) caused a triphasic [Ca2+]i response in single islets at 35 degrees C: an initial decrease and a transient increase followed by a gradual increase, on which series of Ca2+ transients were frequently superimposed. Cooling to 30 and 25 degrees C caused slower and smaller [Ca2+]i responses with a Q10 (temperature coefficient) of 1.8. Glucose caused biphasic insulin secretion at 35 degrees C, which was inhibited by cooling, with a Q10 of 11.6. The ratio of glucose-induced insulin secretion to [Ca2+]i rise (IS/Ca) was calculated to represent the efficiency of Ca2+ to cause exocytosis. The Q10 value of the ratio of IS/Ca was 6.6. The Q10 values of the ratio of IS/Ca in the responses to high K+ (30 mM), carbamylcholine (100 microM) and glibenclamide (2 microM) were 5.6, 3.8, and 13.0, respectively. These values were greater than the Q10 values of corresponding [Ca2+]i responses: 1.2, 1.4, and 1.8, respectively. From these results, we conclude that cooling inhibits not only the glucose-induced [Ca2+]i rise but also Ca(2+)-activated exocytosis, and that the latter is much more sensitive to cooling than the former.
Niwa
K
K
Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Shibuya
I
I
Kanno
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D003080:Cold Temperature; D005089:Exocytosis; D005456:Fluorescent Dyes; D016257:Fura-2; D005947:Glucose / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D005456:Fluorescent Dyes; D007328:Insulin; D002217:Carbachol; D005947:Glucose; D011188:Potassium; D005905:Glyburide; D002118:Calcium; D016257:Fura-2