Direct effect of insulin and insulin-like growth factor-I on the secretory activity of rat pancreatic beta cells.
Purified pancreatic Beta cells were labelled with 3H-tyrosine before studying their secretory activity in perifusion. At 1.4 mmol/l glucose, the cells released similar fractions (0.01% per min) of their contents in preformed and in newly formed insulin. At 20 mmol/l glucose plus 10(-8) mol/l glucagon, these fractional release rates increased by 16 and 40-fold respectively. The preferential release of newly synthesized as compared to stored insulin is attributable to a heterogeneity in individual cell responses. The secretory responsiveness to glucose plus glucagon was completely suppressed by 10(-7) mol/l clonidine. Insulin induced a 20% reduction at 10(-6) mol/l, but remained without effect at 10(-7) mol/l. Insulin-like growth factor-I provoked a 30% decrease at 5.10(-9) mol/l. It is concluded that the type-I insulin-like growth factor receptors on pancreatic Beta cells mediate a suppressive action on the insulin release process. Their high affinity for insulin-like growth factor-I allows physiologic levels of this peptide to participate in the regulation of insulin release. Their low affinity for insulin provides the basis for a minor feedback action by this hormone at concentrations exceeding the normal circulating levels.
Van Schravendijk
C F
CF
Department of Metabolism and Endocrinology, Vrije Universiteit Brussel, Belgium.
Heylen
L
L
Van den Brande
J L
JL
Pipeleers
D G
DG
D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium
D007328:Insulin; D014316:Tritium; D007334:Insulin-Like Growth Factor I; D005934:Glucagon; D005947:Glucose; D003000:Clonidine