Massive augmentation of stimulated insulin secretion induced by fatty acid-free BSA in rat pancreatic islets.
Incubation of rat pancreatic islets for 4-6 h with 100 micromol/l fatty acid-free BSA induced a 3- to 10-fold enhancement of insulin release to a subsequent challenge with 16.7 mmol/l glucose, without changing the typical biphasic pattern of the response. A similar enhancement was observed with other stimuli, such as leucine, depolarizing concentrations of KCl and tolbutamide, pointing to a general phenomenon and common mechanism for the augmentation. Norepinephrine completely blocked the stimulated response. The protein kinase C (PKC) inhibitor Ro 31-8220, which acts at the ATP-binding site and inhibits all PKC isoforms, strongly inhibited the enhancement of a subsequent glucose challenge when present during the BSA pretreatment period. In contrast, Go 6976, an inhibitor of conventional PKC isoforms, was without effect, even at the high concentration of 1 micromol/l. Preincubation with calphostin C, which competes for the diacylglycerol (DAG)-binding site, therefore inhibiting conventional, novel, and PKC isoforms of the PKD type, completely abolished the enhancing effect of the BSA but did not affect secretion in islets treated with 10 micromol/l fatty acid-free BSA. We conclude that the remarkable enhancement of insulin release is due to a change in glucose signaling and activation of a novel PKC isoform or a DAG-binding protein.
Straub
Susanne G
SG
Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. sgs4@cornell.edu
Sharp
Geoffrey W G
GW
D000818:Animals; D003981:Diazoxide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D014044:Tolbutamide / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007211:Indoles; D007328:Insulin; D012710:Serum Albumin, Bovine; D011189:Potassium Chloride; D014044:Tolbutamide; D011493:Protein Kinase C; D003981:Diazoxide; C064758:Ro 31-8220; D009638:Norepinephrine