Respiration and insulin release in mouse pancreatic islets. Effects of L-leucine and 2-ketoisocaproate in combination with D-glucose and L-glutamine.
In order to further evaluate the importance of B-cell metabolism for the stimulation of insulin release, respiration and insulin release were studied in mouse pancreatic islets. Leucine and 2-ketoisocaproate stimulated insulin release during an initial 1-h period, whereas there was no stimulation during two subsequent 1-h periods. This effect was in contrast to that of 16.7 mM glucose, which was a potent stimulator through all the 3 h. Furthermore, the presence of glucose (5.6 mM) or glutamine together with either leucine or 2-ketoisocaproate enhanced the insulin release and prolonged the stimulation. When the kinetics of islet respiration were studied both leucine and 2-ketoisocaproate exerted an initial stimulation on the O2 uptake which, however, was short-lived (less than 30 min). The presence of 5.6 mM glucose strongly delayed the respiratory retardation seen after the initial stimulation. Similarly, glutamine enhanced the leucine- and 2-ketoisocaproate-stimulated respiratory rates and prevented the respiratory retardation otherwise observed. Leucine (20 mM) and 2-ketoisocaproate (10 and 20 mM) stimulated the oxidation of glucose (5.6 mM). It is concluded that there is a strong correlation between respiratory stimulation and the enhancement of insulin release and that leucine and 2-ketoisocaproate depend on the presence of endogenous fuels for their ability to stimulate islet functions in vitro.
D000818:Animals; D002208:Caproates / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D005973:Glutamine / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007651:Keto Acids / Q000494:pharmacology*; D007700:Kinetics; D007930:Leucine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010101:Oxygen Consumption / Q000187:drug effects*
D002208:Caproates; D007328:Insulin; D007651:Keto Acids; D005973:Glutamine; C013082:alpha-ketoisocaproic acid; D007930:Leucine; D005947:Glucose