Stimulation of Insulin Output by Monosaccharides and Monosaccharide Derivatives

Abstract

The ability of various sugars and closely related substances to stimulate insulin secretion was studied by means of pancreatic-femoral cross-circulation experiments between hepatectomized donor dogs and normal recipients. In other experiments, the test substance was injected directly into the pancreatic artery of normal dogs. The administration of d-glucose, d-galactose or d-ribose was followed by a prompt hypoglycemia, suggesting insulin secretion; d-arabinose caused an unexplained delayed hypoglycemia, while d-fructose, d-mannose, d-xylose, l-arabinose, 3-methylglucose, d-glucosamine, galacturonic acid and saline had no effect. The tentative hypothesis that insulin secretion is stimulated by sugars which are both utilizable and insulin-sensitive is offered. No relationship between chemical structure and ability to cause insulin release was found.

Studies on Carbohydrate Metabolism in Patients With Neoplastic Disease. Ii. Reponse to Insulin Administration*†

“…This is indicated by the finding that the ratio of the rate constants, kI/kG, did not differ significantly in the patient and control groups. In view of the evidence that the rate of blood glucose disappearance during hyperglycemia may be determined by endogenous insulin secretion (3,4), these observations are compatible with the concept that impaired glucose tolerance in patients with neoplastic disease may be a manifestation of a decreased responsiveness to endogenous insulin.…”

“…In view of suggestions (3,4) that endogenous insulin secretion determines the rate of blood glucose disappearance, the decreased glucose tolerance might reflect either diminished secretion of, or a diminished responsiveness to, endogenous insulin. On the assumption that sensitivity to exogenously administered insulin reflects responsiveness to the endogenously secreted hormone, insulin response tests have been performed in patients with neoplastic disease.…”

Mannose Utilization in Man*

“…Since mannose does not accelerate peripheral glucose uptake by stimulating measurable release of insulin (19,20) and since small changes in peripheral glucose uptake would normally be compensated by increased hepatic glucose production, these observations suggest that mannose may induce hypoglycemia by decreasing hepatic glucose production. Isotopic studies in vitro (1) have shown almost equal metabolism of glucose and mannose by rat liver slices with mutual competitive inhibition.…”

“…mannose, in contrast to glucose, fails to stimulate measurable pancreatic release of insulin in both dogs . ( 19) and man (20)'. Last, mannose appears in significant amounts in the urine after oral administration (16), suggesting a low or absent renal threshold.…”

Transient Intolerance to Exogenous Fructose in the Newborn *

“…There is evidence suggesting that the hypoglucosemia is not due to increased peripheral uptake. Fructose injected directly into the pancreatic artery of the dog does not produce hypoglucosemia, suggesting that fructose does not stimulate the release of insulini (13). Although the infusion of fructose in nornmal men increases the rate of disappearance of ani exogenous glucose load, an increase in insuliln-like activity in the serum could not be detected (14).…”