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We sought to determine whether treatment of hypoglycemia with a snack containing both protein and carbohydrate results in more prolonged protection against subsequent hypoglycemia than ingestion of carbohydrate alone. We studied six insulin-dependent diabetic subjects on two occasions. On both occasions subjects received a variable overnight insulin infusion to achieve euglycemia followed by a constant insulin infusion (approximately 0.5 mU x kg(-1) x min(-1)) designed to produce hypoglycemia. When glucose reached 50 mg/dL, subjects were fed a snack consisting of either bread (approximately 85 kcal) or bread plus meat (approximately 205 kcal). Both contained 15 g of carbohydrate. The insulin infusion was continued for the next 3 h or until glucose again fell to 50 mg/dL. Although bread plus meat resulted in a more marked rise (P < 0.05) in glucagon than did bread alone, neither the post treatment peak glucose concentration (73 +/- 4 vs. 70 +/- 6 mg/dL) nor the subsequent rate of fall of glucose (0.42 +/- 0.10 us. -0.35 +/- 0.07 mg/dL/min) differed. The present study shows that the rate of redevelopment of hypoglycemia does not differ after eating bread or bread plus meat. Therefore treatment of hypoglycemia with a protein-enriched snack merely adds calories rather prolonged protection against subsequent hypoglycemia.

Insulin-stimulated glucose oxidation is decreased in patients with non-insulin-dependent diabetes mellitus (NIDDM). It is not known whether this decrease is due to a primary defect in the oxidative pathway or is secondary to impaired glucose transport and/or phosphorylation. To address this issue, glucose oxidation was measured under steady-state conditions at low (approximately 270 pmol) and high (approximately 17 mumol) insulin concentrations in seven patients with NIDDM and seven healthy nondiabetic subjects matched for sex, age, and obesity. Glucose oxidation was measured simultaneously by indirect calorimetry and the isotopedilution technique. Although glucose oxidation and nonoxidative storage were lower (P less than 0.05) in diabetic than nondiabetic subjects during the low- and high-dose insulin infusions, oxidation of intracellularly derived glucose, estimated by subtracting the rate of oxidation measured isotopically (i.e., glucose oxidation derived from the extracellular space) from that measured by indirect calorimetry (i.e., total glucose oxidation), did not differ in diabetic and nondiabetic subjects during the low-dose insulin infusion (3.3 +/- 0.1 vs. 3.0 +/- 0.1 mumol.kg-1.min-1). Both techniques provided identical estimates of glucose oxidation during the high-dose insulin infusion. Impaired oxidation of extracellularly but not intracellularly derived glucose strongly suggests that the cause of decreased glucose oxidation in patients with NIDDM is secondary to impaired glucose transport and/or phosphorylation rather than a primary abnormality in the oxidative pathway.

It is well established that patients with non-insulin-dependent diabetes mellitus (NIDDM) are resistant to insulin. However, the contribution of hepatic and extrahepatic tissues to insulin resistance remains controversial. The uncertainty may be at least in part due to errors introduced by the unknowing use in previous studies of impure isotopes to measure glucose turnover. To determine hepatic and extrahepatic responses to insulin in the absence of these errors, steady-state glucose turnover was measured simultaneously with [6-3H]- and [6-14C]glucose during sequential 5- and 4-h infusions of insulin at rates of 0.4 and 10 mU.kg-1.min-1 in diabetic and nondiabetic subjects. At low insulin concentrations, [6-3H]- and [6-14C]glucose gave similar estimates of glucose turnover. Hepatic glucose release was equal to but not below zero in the nondiabetic subjects, but persistent glucose release (P less than 0.001) and decreased glucose uptake (P less than 0.001) was observed in the diabetic patients. At high insulin concentrations, both isotopes underestimated glucose turnover during the 1st h after initiation of the high-dose insulin infusion. More time (P less than 0.05) was required to reachieve steady state in NIDDM than nondiabetic subjects. At steady state, [6-3H]- but not [6-14C]glucose systematically underestimated (P less than 0.05) glucose turnover in both groups due to the presence of a tritiated nonglucose contaminant. The percentage of radioactivity in plasma due to tritiated contaminants was linearly related to turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

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 less than 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 less than 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, beta-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.

A technique of diversion of the gastroduodenal vein in a canine model is described to compare long-term metabolic effects of systemic versus portal pancreatic endocrine drainage. The vein was transected at its entrance into the portal vein and either diverted to the inferior vena cava (systemic group) or reanastomosed to the portal vein (portal group). All remaining venous drainage of the pancreas was interrupted. An additional group of animals underwent laparotomy without manipulation of pancreatic vasculature (sham group). Fasting peripheral insulin and glucose values were determined 3 months postoperatively. Fasting insulin values were significantly higher in the systemic group (mean 10.7 +/- 1.06 U/ml) than in the portal (5.8 +/- 0.70, P = 0.002) and sham (6.4 +/- 0.68, P = 0.01) groups. Fasting glucose values were not significantly different in the three groups. At sacrifice, venous thrombosis was noted in one systemically diverted dog (6.7%). All other anastomoses were patent. No significant collateralization was apparent in any group. No significant complications were noted. This procedure simulates the hormonal milieu created by heterotopic pancreatic transplantation while preserving pancreatic innervation and exocrine function, and serves as an excellent model for investigating the effects of systemic hyperinsulinemia on protein, carbohydrate, and lipid metabolism.