title: Novel effects of insulin secretagogues on capacitation of insulin release and survival of cultured pancreatic islets.
abstract: Agents that stimulate insulin release from fresh pancreatic islets were tested for their ability to capacitate pancreatic islets to secrete insulin and to support beta-cell survival in tissue culture. Capacitation was defined as the ability to release insulin after 24 h in culture in the presence of an insulinotropic concentration of a secretagogue. Viable islets that lose glucose-induced insulin release gradually regain it during culture for 24 h in 20 mM glucose. Survival was defined as the ability to regain glucose-induced insulin release. To measure insulin release after culture, islets were incubated with various secretagogues in Krebs-Ringer buffer for 1 h. Examples of the diverse patterns of responses included the following. Glucose was the only secretagogue that capacitated glucose-induced release. Leucine-, leucine plus glutamine-, and glyceraldehyde-induced release remained capacitated after culture with no secretagogue. Culture at high glucose completely inhibited leucine-induced release. Culture at low glucose (1 mM) or at both high leucine and glutamine abolished glucose-induced release. Only leucine and glutamine capacitated monomethyl succinate-induced release. All agents including subinsulinotropic glucose (1 mM), except D-glyceraldehyde, permitted islet survival. Thus the metabolic pathways for initiation, capacitation, and survival are not identical between and within secretagogues. There is a reciprocal relationship between leucine and glucose with respect to capacitation. Capacitation follows a time course, which suggests that it is regulated by enzyme induction.
authors.affiliation: Department of Pediatrics, University of Wisconsin Medical School, Madison 53706.
authors.forename: M J
authors.initials: MJ
authors.lastname: MacDonald
authors.forename: L A
authors.initials: LA
authors.lastname: Fahien
authors.forename: D I
authors.initials: DI
authors.lastname: McKenzie
authors.forename: S M
authors.initials: SM
authors.lastname: Moran
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D005973:Glutamine / Q000494:pharmacology; D005985:Glyceraldehyde / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D007930:Leucine / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013386:Succinates / Q000494:pharmacology
chemical_list: D007328:Insulin; D013386:Succinates; D005973:Glutamine; D005985:Glyceraldehyde; D007930:Leucine; D005947:Glucose; C041105:monomethyl succinate