Interplay of nutrients and hormones in the regulation of insulin release

Endocrinology. 1985 Sep;117(3):824-33. doi: 10.1210/endo-117-3-824.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / pharmacology*
  • Animals
  • Arginine / pharmacology
  • Bucladesine / pharmacology
  • Cyclic AMP / metabolism
  • Epinephrine / pharmacology
  • Flow Cytometry
  • Glucagon / pharmacology
  • Glucose / pharmacology*
  • In Vitro Techniques
  • Insulin / metabolism*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Leucine / pharmacology
  • Male
  • Microscopy, Electron
  • Pancreatic Hormones / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Somatostatin / pharmacology

Substances

  • Amino Acids
  • Insulin
  • Pancreatic Hormones
  • Somatostatin
  • Bucladesine
  • Glucagon
  • Arginine
  • Cyclic AMP
  • Leucine
  • Glucose
  • Epinephrine