Interleukin 1 is a potent stimulator of islet insulin secretion and phosphoinositide hydrolysis.
The insulin stimulatory effect of 7 mM glucose on isolated perifused rat islets is dramatically potentiated by the monokine interleukin 1 (IL-1). At levels (10(-10) -10(-8) M) noted in vivo during sepsis, it reversibly amplifies peak second phase insulin release to the hexose. At 2.75 mM glucose, however, IL-1 has no effect on insulin secretion. IL-1 also potentiates glyceraldehyde (2 mM)- and alpha-ketoisocaproate (5 mM)-induced insulin secretion. In islets whose phosphoinositides were prelabeled with myo-[2-3H]inositol, 2.0-5.0 nM IL-1 increases the efflux of [3H]inositol from subsequently perifused islets, the parallel accumulation of labeled inositol phosphates, and insulin secretion in the simultaneous presence of 7 mM glucose but not 2.75 mM glucose. In support of these in vitro observations, the in vivo infusion of IL-1 (40 micrograms/kg body wt) elevated circulating plasma insulin levels two-to fourfold. These results establish IL-1 as a potent, readily reversible, glucose-dependent modulator of stimulated insulin secretion and further suggest that its positive impact on insulin release is mediated, at least in part, by phosphoinositide-derived second messenger molecules. IL-1-induced insulin secretion may participate in the multiple metabolic and immunologic adaptations occurring during sepsis.
Zawalich
W S
WS
Yale University School of Nursing, New Haven, Connecticut 06536-0740.
Zawalich
K C
KC
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D005985:Glyceraldehyde / Q000494:pharmacology; D006868:Hydrolysis; D007294:Inositol / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007651:Keto Acids / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D007375:Interleukin-1; D007651:Keto Acids; D010716:Phosphatidylinositols; D005985:Glyceraldehyde; D007294:Inositol; C013082:alpha-ketoisocaproic acid; D005947:Glucose