ISSN:
1432-0428
Keywords:
Pancreatic islets
;
insulin release
;
interleukin-1β
;
glucose metabolism
;
amino acid metabolism
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary Acute exposure of pancreatic islets to interleukinl-1β results in an increase in insulin release, while an extension of the exposure time induces a functional suppression and eventually, destruction of the B-cells. We have recently suggested that the interleukin-1β induced inhibition of islet function is mediated through an impairment in oxidative metabolism. The aim of the current study was to investigate if the acute, stimulatory effects of interleukin-1β on islet function could also be related to changes in the substrate metabolism. For this purpose, rat islets were exposed for 90–120 min to 30 pmol/l human recombinant interleukin-1β (biological activity of 2.5 U/ml) and their function and metabolism characterized during this period. The cytokine did not increase insulin release in the presence of 1.7 or 5.5 mmol/l glucose but in both the presence of 16.7 mmol/l glucose or 10 mmol/l leucine + 2 mmol/l glutamine there was a 50% increase in insulin release. Interleukin-1β exposure increased the oxidation of D-[U-14C]glucose at 5.5 mmol/l glucose by 25% and at 16.7 mmol/l glucose by 60%. Carbohydrate and amino acid metabolism were further examined in the presence of D-[5-3H] glucose, D-[6-14C]glucose, [1-14C]pyruvate, L-[U-14C]glutamine, L-[U-14C]leucine and L-[1-14C]leucine. There was no difference between control islets and interleukin-1β exposed islets in terms of D-[5-3H]glucose utilization or [1-14C]pyruvate decarboxylation, but the oxidation of D-[6-14C]glucose was increased by 64% in the interleukin-1β exposed islets. There was also an interleukin-1β induced 45–60% increase in the decarboxylation of L-[1-14C]leucine and oxidation of L-[U-14C]leucine and L-[U-14C]glutamine, all intramitochrondrial events. The stimulation of insulin release by interleukin-1β in the presence of 16.7 mmol/l glucose was abolished in islets incubated in Ca2+ depleted medium, but the rate of D-[6-14C] glucose oxidation remained elevated (47% increase at 16.7 mmol/l glucose). These data indicate an increase in substrate metabolism at the mitochondrial level during acute exposure of rat pancreatic islets to interleukin-1β. The increase in oxidative events can explain the observed interleukin-1β induced increase in insulin release during glucose stimulation. Furthermore, these findings raise the possibility that mitochondria are primary targets of interleukin-1β action in the B-cells.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00264905
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