Human interleukin 1 beta stimulates islet insulin release by a mechanism not dependent on changes in phospholipase C and protein kinase C activities or Ca2+ handling.
Isolated islets from adult rats or obese hyperglycemic (ob/ob) mice were incubated with human recombinant interleukin 1 beta in order to study whether the acute effects of the cytokine on islet insulin release are associated with changes in islet phospholipase C activity, Ca2+ handling or protein phosphorylation. The cytokine stimulated insulin release both at low and high glucose concentrations during one hour incubations. In short-term incubations (less than 1 min) interleukin 1 beta did not affect the production of inositoltrisphosphate. Addition of interleukin 1 beta affected neither the cytoplasmic free Ca2+ concentration at rest nor that observed subsequent to stimulation with a high concentration of glucose. Furthermore, the endogenous protein kinase C activity, as visualized by immunoprecipitation of a 32P-labelled substrate for this enzyme, was not altered by interleukin 1 beta. Separation of 32P-labelled proteins by means of 2-dimensional gel electrophoresis failed to reveal any specific effects of the cytokine on the total protein phosphorylation activity. These results suggest that the stimulatory effects on insulin release exerted by interleukin 1 beta are not caused by acute activation of phospholipase C and protein kinase C or by an alteration of islet Ca2+ handling of the B-cells.
Welsh
N
N
Department of Medical Cell Biology, Uppsala University, Sweden.
Nilsson
T
T
Hallberg
A
A
Arkhammar
P
P
Berggren
P O
PO
Sandler
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D051379:Mice; D008820:Mice, Obese; D010750:Phosphoproteins / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D010738:Type C Phospholipases / Q000378:metabolism*
D007295:Inositol Phosphates; D007328:Insulin; D007375:Interleukin-1; D010750:Phosphoproteins; D011493:Protein Kinase C; D010738:Type C Phospholipases; D002118:Calcium