Faculty Collaboration Database

Biochemical evidence for nitric oxide formation from streptozotocin in isolated pancreatic islets. Biochem Biophys Res Commun 1993 Dec 30;197(3):1458-64

Date

12/30/1993

Pubmed ID

7904159

DOI

10.1006/bbrc.1993.2641

Scopus ID

2-s2.0-0027739947 (requires institutional sign-in at Scopus site)   187 Citations

Abstract

Streptozotocin (STZ) is selectively toxic to insulin-secreting beta-cells of pancreatic islets and induces impairment of islet glucose oxidation and of glucose-induced insulin secretion. Similar effects are induced by Interleukin-1 (IL-1), and the deleterious effects of IL-1 on islets appear to be mediated by nitric oxide (NO). STZ contains a nitroso moiety and may liberate NO by processes analogous to those for the NO-releasing drug nitroprusside. NO is rapidly transformed to nitrite in aqueous solution, and NO activates heme-containing enzymes such as guanylyl cyclase and inhibits iron-sulfur enzymes such as mitochondrial aconitase. Data presented here indicate that incubation of rat islets with STZ at concentrations that impair insulin secretion results in generation of nitrite, stimulation of islet guanylyl cyclase and accumulation of cGMP, and inhibition of islet mitochondrial aconitase activity to a degree similar to that achieved by IL-1. Effects of STZ on beta-cells may be mediated by local liberation of NO from STZ within islets.

Author List

Turk J, Corbett JA, Ramanadham S, Bohrer A, McDaniel ML

Author

John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aconitate Hydratase
Animals
Cyclic GMP
Guanylate Cyclase
Humans
In Vitro Techniques
Insulin
Interleukin-1
Islets of Langerhans
Kinetics
Male
Mitochondria
Nitric Oxide
Nitrites
Nitroprusside
Rats
Rats, Sprague-Dawley
Recombinant Proteins
Streptozocin