Polonsky, Kenneth S.

The importance of portal insulin delivery in the regulation of postprandial carbohydrate metabolism is uncertain. To address this question, three groups of dogs were studied: one group in which pancreatic venous drainage was transected and reanastomosed (portal insulin delivery), one in which the pancreatic drainage was transected and anastomosed to the inferior vena cava (peripheral insulin delivery), and one that received only a sham operation. Plasma insulin was greater (P < 0.05) during peripheral insulin delivery than in either the portal or sham groups, respectively, before and after meal ingestion. On the other hand, C-peptide concentrations did not differ between groups, resulting in a higher (P < 0.001) insulin to C-peptide ratio in the peripheral group. This indicated that the hyperinsulinemia in the peripheral group was due to decreased insulin clearance rather than increased insulin secretion. Isotopically determined splanchnic uptake of ingested glucose, postprandial suppression of hepatic glucose release, incorporation of CO2 into glucose (a qualitative measure of gluconeogenesis), and total-body glucose uptake were virtually identical in all groups. Similarly, plasma lipid, β-hydroxybutyrate, and lactate concentrations did not differ between groups. Our data indicate that, despite differences in systemic insulin concentration, portal and peripheral insulin delivery comparably regulate hepatic and extrahepatic carbohydrate metabolism after meal ingestion.

Highly informative yet simple protocols to assess insulin secretion and action would considerably enhance the quality of epidemiological and large-scale clinical trials. In an effort to develop such protocols, a 5-h, 11-sample oral glucose tolerance test (OGTT) was performed in 100 individuals and a 7-h, 21-sample meal in another 100. Plasma glucose, insulin, and C-peptide concentrations were measured. We show that virtually the same minimal model assessment of β-cell responsivity (dynamic [Φd] and static [Φs]), insulin sensitivity (Si), and disposition index (DI) can be obtained with a reduced seven-sample 2-h protocol: Φd, reduced versus full: 871.50 vs. 873.32, r = 0.98 in OGTT and 494.88 vs. 477.99 10−9, r = 0.91 in meal; Φs: 42.36 vs. 44.35, r = 0.88 in OGTT and 35.31 vs. 35.37 10−9 min−1, r = 0.90 in meal; Si: 24.33 vs. 22.77 10−5 dl · kg−1 · min−1 per pmol/l, r = 0.89 in OGTT and 19.03 vs. 19.77 10−5 dl · kg−1 · min−1 per pmol/l, r = 0.85 in meal; and DI: 1,282.26 vs. 1,273.23, r = 0.84 in OGTT and 726.92 vs. 776.97 10−14 dl · kg−1 · min−2 per pmol/l, r = 0.84 in meal. This reduced protocol will facilitate the study of insulin secretion and action under physiological conditions in nondiabetic humans.