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J Clin Invest. 2000 Aug;106(3):373-84.

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

Author information

1
Department of Neuroscience, The Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.

Erratum in

  • J Clin Invest 2000 Sep;106(6):803.

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.

PMID:
10930440
PMCID:
PMC314323
DOI:
10.1172/JCI8273
[Indexed for MEDLINE]
Free PMC Article

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