Insulin restores neuronal nitric oxide synthase expression and function that is lost in diabetic gastropathy. Academic Article uri icon

Overview

abstract

  • Gastrointestinal dysfunction is common in diabetic patients. In genetic (nonobese diabetic) and toxin-elicited (streptozotocin) models of diabetes in mice, we demonstrate defects in gastric emptying and nonadrenergic, noncholinergic relaxation of pyloric muscle, which resemble defects in mice harboring a deletion of the neuronal nitric oxide synthase gene (nNOS). The diabetic mice manifest pronounced reduction in pyloric nNOS protein and mRNA. The decline of nNOS in diabetic mice does not result from loss of myenteric neurons. nNOS expression and pyloric function are restored to normal levels by insulin treatment. Thus diabetic gastropathy in mice reflects an insulin-sensitive reversible loss of nNOS. In diabetic animals, delayed gastric emptying can be reversed with a phosphodiesterase inhibitor, sildenafil. These findings have implications for novel therapeutic approaches and may clarify the etiology of diabetic gastropathy.

publication date

  • August 1, 2000

Research

keywords

  • Diabetes Mellitus
  • Insulin
  • Nitric Oxide Synthase
  • Stomach Diseases

Identity

PubMed Central ID

  • PMC314323

Scopus Document Identifier

  • 0033847010

Digital Object Identifier (DOI)

  • 10.1172/JCI8273

PubMed ID

  • 10930440

Additional Document Info

volume

  • 106

issue

  • 3