Interleukin 1 is a potent stimulator of islet insulin secretion and phosphoinositide hydrolysis

• Published in: The American journal of physiology Vol. 256; no. 1 Pt 1; p. E19
• Main Authors: Zawalich, W S, Zawalich, K C
• Format: Journal Article
• Language: English
• Published: United States 01.01.1989
• Subjects: Animals; Dose-Response Relationship, Drug; Drug Synergism; Glucose - administration & dosage; Glucose - pharmacology; Glyceraldehyde - pharmacology; Hydrolysis; Inositol - metabolism; Insulin - metabolism; Insulin Secretion; Interleukin-1 - administration & dosage; Interleukin-1 - pharmacology; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Keto Acids - pharmacology; Kinetics; Male; Phosphatidylinositols - metabolism; Rats; Rats, Inbred Strains
• ISSN: 0002-9513; 2163-5773
• DOI: 10.1152/ajpendo.1989.256.1.e19

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.