Kinetics of insulin secretion in chronic pancreatitis and mild maturity onset diabetes. (Evidence for "gut hormone" action beyond glucoreceptor and cyclic adenosine monophosphate mediated insulin release).
We studied insulin responses to glucose with and without cholecystokinin-pancreozymin and aminophyllin infusions in normal, chronic pancreatitic and genetic (maturity-onset) diabetic subjects. Glucose was given alone as separate 5 and 10 g boluses followed by infusion at 250 mg/min. and 500 mg/min., respectively. Chronic pancreatitis patients and genetic diabetic patients had decreased Imax values, indicating a decreased insulin reserve. Sensitivity to glucose was normal in pancreatitic subjects, but the diabetic subjects had a raised G50 value, compatible with glucoreceptor dysfunction. Infusions of aminophyllin enhanced insulin responses (Imax) to glucose injection in normal subjects and to a lesser degree in pancreatitic subjects, but decreased sensitivity to glucose (increase in G50) in both groups. Although the Imax value in pancreatitic subjects was significantly lower than in the control subjects during the glucose plus aminophyllin infusion, the blood glucose concentration in the pancreatitic subjects was nonetheless decreased. This suggests that pancreatitic subjects have increased endogenous insulin sensitivity. Aminophyllin had no effect in diabetic subjects. Crude cholecystokinin-pancreozymin changed the shape of the glucose/insulin dose response curve in normal, pancreatitic and diabetic subjects. These findings further suggest that the defect in insulin secretion in pancreatitic subjects is partly situated at the cyclic adenosine monophosphate stage of insulin release. Crude cholecystokin-pancreozymin seems to affect insulin release at a point beyond the cyclic adenosine monophosphate stage.
D000328:Adult; D000628:Aminophylline / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology; D002908:Chronic Disease; D000242:Cyclic AMP / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism*; D005768:Gastrointestinal Hormones / Q000502:physiology*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000378:metabolism*; D011955:Receptors, Drug
D005768:Gastrointestinal Hormones; D007328:Insulin; D011955:Receptors, Drug; D000628:Aminophylline; D002766:Cholecystokinin; D000242:Cyclic AMP; D005947:Glucose