TY - JOUR
T1 - Insulin restores neuronal nitric oxide synthase expression and function that is lost in diabetic gastropathy
AU - Watkins, Crystal C.
AU - Sawa, Akira
AU - Jaffrey, Samie
AU - Blackshaw, Seth
AU - Barrow, Roxanne K.
AU - Snyder, Solomon H.
AU - Ferris, Christopher D.
PY - 2000
Y1 - 2000
N2 - 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 phos-phodiesterase inhibitor, sildenafil. These findings have implications for novel therapeutic approaches and may clarify the etiology of diabetic gastropathy.
AB - 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 phos-phodiesterase inhibitor, sildenafil. These findings have implications for novel therapeutic approaches and may clarify the etiology of diabetic gastropathy.
UR - http://www.scopus.com/inward/record.url?scp=0033847010&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033847010&partnerID=8YFLogxK
U2 - 10.1172/JCI8273
DO - 10.1172/JCI8273
M3 - Article
C2 - 10930440
AN - SCOPUS:0033847010
SN - 0021-9738
VL - 106
SP - 373
EP - 384
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 3
ER -