Novel effects of insulin secretagogues on capacitation of insulin release and survival of cultured pancreatic islets.
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.
MacDonald
M J
MJ
Department of Pediatrics, University of Wisconsin Medical School, Madison 53706.
Fahien
L A
LA
McKenzie
D I
DI
Moran
S M
SM
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
D007328:Insulin; D013386:Succinates; D005973:Glutamine; D005985:Glyceraldehyde; D007930:Leucine; D005947:Glucose; C041105:monomethyl succinate