The same dose of glucose given intravenously or orally produced a similar increase in serum insulin, although the blood glucose level was much lower after oral administration than after intravenous administration. These findings support the hypothesis that an additional insulinotropic mechanism other than hyperglycemia is associated with the oral administration of glucose. The specificity of this mechanism was investigated by examining the insulin response following oral and intravenous infusions of various monosaccharides other than glucose, e.g., mannose, fructose, galactose, α-methyl glucoside, ribose and xylose. Oral infusion of these monosaccharides, except mannose and fructose, produced a progressive rise in the blood level of the monosaccharides. All monosaccharides examined except α-methyl glucoside led to an increase in serum insulinlevel when given intravenously. However, after oral administration only glucose, galactose and xylose led to an increase in serum insulin, whereas mannose, fructose and ribose had no effect. These findings suggest that the proposed insulinotropic mechanism elicited by oral administration is not specific to glucose but does require an increase in the blood saccharide level after oral administration. However, oral infusion of the sugar analogue, α-methyl glucoside, did not promote insulin secretion despite rapid absorption and marked increase in its level in the blood. This suggests that a sugar, in addition to being absorbed with subsequent increase in blood level, must possess an active reducing group for the elicitation of insulin release.
The intravenous infusion of readily metabolizable sugar (glucose, mannose and fructose) produced marked insulin response whereas similar infusion of xylose, ribose, and galactose elicited only a moderate insulin response. The intravenous injection of a nonmetabolizable sugar, α-methyl glucoside, had no stimulatory effect. These findings suggest that the rise in blood saccharidelevel per se after intravenous administration may not be the sole stimulus for insulin secretion but possibly a metabolite of the infused sugar is a stimulus. This inference was supported by the finding that the intravenous injection of pyruvate enhanced the secretion of insulin.