1. Interleukin-1 Reduces the Glycolytic Utilization of Glucose by Pancreatic Islets and Reduces Glucokinase mRNA Content and Protein Synthesis by a Nitric Oxide-dependent Mechanism
- Author
-
John Turk, Zhongmin Ma, Sasanka Ramanadham, David M. Kipnis, Alan Bohrer, and Michael Landt
- Subjects
Male ,endocrine system ,medicine.medical_specialty ,endocrine system diseases ,Biology ,Nitric Oxide ,Polymerase Chain Reaction ,Biochemistry ,Nitric oxide ,Rats, Sprague-Dawley ,Islets of Langerhans ,chemistry.chemical_compound ,Internal medicine ,Glucokinase ,medicine ,Animals ,Glycolysis ,RNA, Messenger ,Enzyme Inhibitors ,Molecular Biology ,geography ,omega-N-Methylarginine ,geography.geographical_feature_category ,Hydroxyl Radical ,Pancreatic islets ,Interleukin ,Cell Biology ,Islet ,Rats ,Nitric oxide synthase ,Glucose ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Protein Biosynthesis ,biology.protein ,Arachidonic acid ,Nitric Oxide Synthase ,Interleukin-1 - Abstract
Culture of rat pancreatic islets with interleukin-1 (IL-1) results in up-regulation of the inducible isoform of nitric oxide synthase and overproduction of nitric oxide (NO). This is associated with reversible inhibition of both glucose-induced insulin secretion and islet glucose oxidation, and these effects are prevented by the inducible nitric oxide synthase inhibitorN G-monomethylarginine. IL-1 also induces accumulation of nonesterified arachidonic acid in islets by an NO-dependent mechanism, and one potential explanation for that effect would involve an IL-1-induced enhancement of islet glycolytic flux. We have therefore examined effects of IL-1 on islet glycolytic utilization of glucose and find that culture of islets with IL-1 in medium containing 5.5 mm glucose results in suppression of islet glucose utilization subsequently measured at glucose concentrations between 6 and 18 mm. The IL-1-induced suppression of islet glucose utilization is associated with a decline in islet glucokinase mRNA content, as determined by competitive reverse transcriptase-polymerase chain reaction, and in glucokinase protein synthesis, as determined by immuoprecipitation experiments, and all of these effects are prevented byN G-monomethylarginine. These findings suggest that IL-1 can down-regulate islet glucokinase, which is the primary component of the islet glucose-sensor apparatus, by an NO-dependent mechanism. Because reductions in islet glucokinase levels are known to cause a form of type II diabetes mellitus, these observations raise the possibility that factors which increase islet NO levels might contribute to development of glucose intolerance.
- Published
- 1997