title: Interleukin-1 beta depletes insulin messenger ribonucleic acid and increases the heat shock protein hsp70 in mouse pancreatic islets without impairing the glucose metabolism.
abstract: In order to further characterize the actions of recombinant interleukin-1 beta (rIL-1 beta) on the function of insulin-producing cells, the effects of different concentrations of the cytokine were studied on islets obtained from four different mouse strains (NMRI, NOD, C57BL/6, and C57BL/Ks). For this purpose the islets were exposed to rIL-1 beta (25, 50, or 100 U/ml) for a 48-h period in medium RPMI 1640 containing 10% calf serum and 11.1 mM glucose. In all groups and at the various rIL-1 beta concentrations tested, there was a similar 30-50% inhibition in glucose-induced insulin release, a 70-80% decrease in islet insulin content, and no significant differences in islet DNA content or insulin accumulation in the culture medium. To clarify the mechanisms underlying the decreased islet insulin content, rates of (pro)insulin biosynthesis and insulin messenger RNA (mRNA) contents were determined. Exposure of NMRI and C57BL/6 islets to 50 U/ml rIL-1 beta reduced the (pro)insulin biosynthesis by 40-50% and the insulin mRNA contents by 80-90%. The cytokine also induced an increased cellular content of the heat shock protein hsp70, as measured by western blot analysis, and a decrease in DNA biosynthesis, as measured by [methyl-3H]thymidine incorporation. However, exposure to rIL-1 beta did not decrease islet total protein biosynthesis, glucose oxidation, ATP content, ATP/ADP ratio, cAMP content, or polyamine contents. In conclusion, these data suggest that exposure of mouse islets to rIL-1 beta reduces DNA synthesis, insulin mRNA levels, and the biosynthesis of (pro)insulin, without equally impairing other cellular functions. The mechanisms behind these reductions seem to be different from those observed in rat islets, where a rIL-1 beta-induced impairment of substrate metabolism at the mitochondrial level seems to be related to the decrease of several cellular functions.
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Sweden.
authors.forename: D L
authors.initials: DL
authors.lastname: Eizirik
authors.forename: M
authors.initials: M
authors.lastname: Welsh
authors.forename: E
authors.initials: E
authors.lastname: Strandell
authors.forename: N
authors.initials: N
authors.lastname: Welsh
authors.forename: S
authors.initials: S
authors.lastname: Sandler
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D005947:Glucose / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007328:Insulin / Q000096:biosynthesis / Q000235:genetics*; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins
chemical_list: D006360:Heat-Shock Proteins; D007328:Insulin; D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D004247:DNA; D000242:Cyclic AMP; D005947:Glucose