Interplay of nutrients and hormones in the regulation of insulin release.
Single pancreatic B cells are purified by autofluorescence-activated cell sorting, and their secretory activity is measured after overnight culture. Compared to intact islets, the isolated cells release 2-fold more insulin under basal conditions and 5-fold less during nutrient stimulation. Their secretory activity can be induced by glucose, leucine, or arginine, but only 0.3-1.7% of their hormone content is liberated at 20 mM nutrient concentrations. This poor nutrient-induced insulin release from purified B cells is attributed to their low cAMP levels and is markedly increased after addition of (Bu)2cAMP, of glucagon, or of pancreatic A cells. These results strongly support the concept that the potent in vivo insulin-releasing action of glucose and leucine is not only dependent on their fuel capacity in pancreatic B cells but also on the concurrent cAMP levels in these cells. In isolated islets, endogenously released glucagon apparently determines the cAMP production in B cells and thus participates in the nutrient-induced secretory process. Somatostatin and epinephrine were shown to exert their suppressive effects via the glucagon-dependent messenger system. It is concluded that nutrients and hormones interact with two different messenger systems which amplify each others' stimulatory effect upon insulin release. cAMP might represent the hormone-induced messenger which sets the B cell's sensitivity and secretory capacity for nutrient stimuli such as glucose. The higher insulin secretory response observed after reaggregation of single B cells could not be attributed to an altered activity in the nutrient or hormonal regulatory units, raising the possibility that the aggregated state of the cells is rather responsible for a better organization or cooperation of the secretory effector unit.
Pipeleers
D G
DG
Schuit
F C
FC
in't Veld
P A
PA
Maes
E
E
Hooghe-Peters
E L
EL
Van de Winkel
M
M
Gepts
W
W
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D005434:Flow Cytometry; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007930:Leucine / Q000494:pharmacology; D008297:Male; D008854:Microscopy, Electron; D010187:Pancreatic Hormones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000494:pharmacology
D000596:Amino Acids; D007328:Insulin; D010187:Pancreatic Hormones; D013004:Somatostatin; D003994:Bucladesine; D005934:Glucagon; D001120:Arginine; D000242:Cyclic AMP; D007930:Leucine; D005947:Glucose; D004837:Epinephrine