Insulin Metabolism Is a Major Factor Responsible for High or Low Peripheral Insulin Levels in Response to Oral Glucose Loading in the Healthy Man

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Abstract
In the present study we evaluated C-peptide peripheral levels after an oral glucose load in 30 healthy subjects (18 females, 12 males, aged from 15 to 55) with high or low insulin response to glucose challenge in order to clarify whether or not their .beta.-cell secretion rate keeps pace with peripheral insulin levels. Moreover, by the study of the relations between C-peptide and insulin in peripheral blood, we had an insight into the extent of insulin metabolism. On the basis of an insulin incremental area higher or lower than the mean .+-. 1 SD after a 100-gram oral glucose load, 6 subjects were classified as ''high insulin responders'' and 6 other subjects as ''low insulin responders''. Their insulin incremental area after glucose averaged 0.25 .+-. 0.01 nmol .cntdot. l-1 .cntdot. min and 0.078 and .+-. 0.005 nmol .cntdot. l-1 min .cntdot. respectively (p < 0.001). The two groups were matched for sex, age and body weight. The glycemic profile after oral glucose load was higher in low insulin responders than in high insulin responders. C-peptide concentrations after glucose load were similar in the two groups, as well as C-peptide incremental areas (0.92 .+-. 0.12 vs. 0.74 .+-. 0.08 nmol .cntdot. l-1 .cntdot. min in high insulin responders and low insulin responders, respectively). The molar ratios of C-peptide to insulin after oral glucose load, as well as the relations between the incremental areas of the two peptides, were significantly lower in high insulin responders than in low insulin responders. We conclude that in the healthy man a ''low'' or ''high'' peripheral insulin response to oral glucose loading is not synonymous with decreased or exaggerated production and/or release of insulin by the pancreatic .beta.-cell. Differences in the metabolic clearance rate of insulin seem primarily to account for the great variability of peripheral insulin levels after glucose challenge.