Evidence for cholinergic and vagal noncholinergic mechanisms modulating plasma motilin-like immunoreactivity.
Basal concentrations of plasma motilin-like immunoreactivity (MLI) and responses to insulin-induced hypoglycemia were measured in healthy subjects (n = 13) in diabetics with clinical evidence of autonomic neuropathy (AN; n = 7), in diabetics without AN (n = 9), and in five recently (6--12 months) vagotomized subjects. Mean basal MLI concentrations were similar in the healthy subjects (141 +/- 21.5 pg/ml) and diabetics without AN (124 +/- 22.4 pg/ml), but were significantly higher in diabetics with AN (349 +/- 71.5 pg/ml) and in vagotomized subjects (381 +/- 47.6 pg/ml). In both healthy subjects and diabetics without AN, the acute administration of insulin (0.1--0.2 U/kg) caused a fall in the mean MLI concentration, reaching a nadir within 20 min, returning to the basal concentration by 60 min, and rising above basal levels by 90 min. In diabetics with AN and vagotomized subjects, the fall in MLI persisted for 90 min. Intravenous atropine administered 15 min after the insulin injection in healthy subjects did not impair the return to basal. The responses were not related to the degree of hypoglycemia, the absolute or relative fall in blood glucose concentrations, or differences in blood glucose among healthy subjects, diabetics, or vagotomized subjects. It appears, therefore, that insulin lowers plasma MLI levels, which are restored to basal by a vagal noncholinergic mechanism. Furthermore, the vagus exerts a suppressive effect on basal MLI levels, and vagotomy and diabetic autovagotomy are associated with abnormal elevation of MLI levels. Since motilin is thought to be important in interdigestive intestinal motility, abnormalities in MLI secretion in diabetics with autonomic neuropathy may contribute to gastrointestinal stasis and erratic diabetic control.
D001285:Atropine / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood; D003929:Diabetic Neuropathies / Q000097:blood; D005768:Gastrointestinal Hormones / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D009037:Motilin / Q000097:blood*; D011950:Receptors, Cholinergic / Q000502:physiology*; D013997:Time Factors; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*
D001786:Blood Glucose; D005768:Gastrointestinal Hormones; D007328:Insulin; D011950:Receptors, Cholinergic; D009037:Motilin; D001285:Atropine