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The vascular endothelium is a site of pathological changes in patients with diabetes mellitus that may be related to severe chronic hyperglycemia. However, it is unclear whether transient hyperglycemia alters vascular function in an otherwise healthy human forearm. To test the hypothesis that acute, moderate hyperglycemia impairs endothelium-dependent forearm vasodilation, we measured vasodilator responses in 25 healthy volunteers (11 F, 14 M) assigned to one of three protocols. In protocol 1, glucose was varied to mimic a postprandial pattern (i.e., peak glucose ~11.1 mmol/l) commonly observed in individuals with impaired glucose tolerance. Protocol 2 involved 6 h of mild hyperglycemia (~7 mmol/l). Protocol 3 involved 6 h of euglycemia. Glucose concentration was maintained with a variable systemic glucose infusion. Insulin concentrations were maintained at ~65 pmol/l by means of a somatostatin and 'basal' insulin infusion. Glucagon and growth hormone were replaced at basal concentrations. Forearm blood flow (FBF) was calculated from Doppler ultrasound measurements at the brachial artery. In each protocol, FBF dose responses to intrabrachial acetylcholine (ACh) and sodium nitroprusside (NTP) were assessed at baseline and at 60, 180, and 360 min of glucose infusion. Peak endothelium-dependent vasodilator responses to ACh were not diminished by hyperglycemia in any trial. For example, peak responses to ACh during protocol 2 were 307 [+ or -] 47 ml/min at euglycemic baseline and 325 [+ or -] 52, 353 [+ or -] 65, and 370 [+ or -] 70 ml/min during three subsequent hyperglycemic trials (P = 0.46). Peak endothelium-independent responses to NTP infusion were also unaffected. We conclude that acute, moderate hyperglycemia does not cause short-term impairment of endothelial function in the healthy human forearm. endothelial function; vasodilation; postprandial hyperglycemia

Portal infusion of glucose at rates approximating endogenous glucose production (EGP) causes paradoxical hypoglycemia in wild-type but not GLUT2 null mice, implying activation of a specific portal glucose sensor. To determine whether this occurs in humans, glucose containing [3-[sup.3]H]glucose was infused intraduodenally at rates of 3.1 mg*[kg.sup.-1]*[min.sup.-1] (n = 5), 1.55 mg*[kg.sup.-1]*[min.sup.-1] (n = 9), or 0/0.1 mg*[kg.sup.-1]* [min.sup.-1] (n = 9) for 7 h in healthy nondiabetic subjects. [6,6-[sup.2][H.sub.2]]glucose was infused intravenously to enable simultaneous measurement of EGP, glucose disappearance, and the rate of appearance of the intraduodenally infused glucose. Plasma glucose concentrations fell (P < 0.01) from 90 [+ or -] 1 to 84 [+ or -] 2 mg/dl during the 0/0.1 mg*[kg.sup.-1]*[min.sup.-1] id infusions but increased (P < 0.001) to 104 [+ or -] 5 and 107 [+ or -] 3 mg/dl, respectively, during the 1.55 and 3.1 mg*[kg.sup.-1]*[min.sup.-1] id infusions. In contrast, insulin increased (P < 0.05) during the 1.55 and 3.0 mg*[kg.sup.-1]*[min.sup.-1] infusions, reaching a peak of 10 [+ or -] 2 and 18 [+ or -] 5 [micro]U/ml, respectively, by 2 h. Insulin concentrations then fell back to concentrations that no longer differed by study end (7 [+ or -] 1 vs. 8 [+or 1] [micro]U/ml). This resulted in comparable suppression of EGP by study end (0.84 [+or 1] 0.2 and 0.63 [+ or -] 0.1 mg*[kg.sup.-1])*[min.sup.-1]). Glucose disappearance was higher (P < 0.01) during the final hour of the 3.1 than 1.55 mg*[kg.sup.-1])*[min.sup.-1] id infusion (4.47 [+ or -] 0.2 vs. 2.6 [+ or -] 0.1 mg*[kg.sup.-1])*[min.sup.-1], likely because of the slightly, but not significantly, higher glucose and insulin concentrations. We conclude that, in contrast to mice, selective portal glucose delivery at rates approximating EGP does not cause hypoglycemia in humans. portal signal; splanchnic glucose extraction; glucose uptake; endogenous glucose production

Portal infusion of glucose at rates approximating endogenous glucose production (EGP) causes paradoxical hypoglycemia in wild-type but not GLUT2 null mice, implying activation of a specific portal glucose sensor. To determine whether this occurs in humans, glucose containing [3-³H]glucose was infused intraduodenally at rates of 3.1 mg·kg[sup -1] · min[sup -1] (n = 5), 1.55 mg·kg[sup -1]·min[sup -1] (n = 9), or 0/0.1 mg·kg[sup -1]·min[sup -1] (n = 9) for 7 h in healthy nondiabetic subjects. [6,6-²H[sub 2]]glucose was infused intravenously to enable simultaneous measurement of EGP, glucose disappearance, and the rate of appearance of the intraduodenally infused glucose. Plasma glucose concentrations fell (P < 0.01) from 90 ± 1 to 84 ± 2 mg/dl during the 0/0.1 mg·kg[sup -1]·min[sup -1] id infusions but increased (P < 0.001) to 104 ± 5 and 107 ± 3 mg/dl, respectively, during the 1.55 and 3.1 mg·kg[sup -1]·min[sup -1] id infusions. In contrast, insulin increased (P < 0.05) during the 1.55 and 3.0 mg·kg[sup -1]·min[sup -1] infusions, reaching a peak of 10 ± 2 and 18 ± 5 µU/ml, respectively, by 2 h. Insulin concentrations then fell back to concentrations that no longer differed by study end (7 ± 1 vs. 8 ± 1 µU/ml). This resulted in comparable suppression of EGP by study end (0.84 ± 0.2 and 0.63 ± 0.1 mg·kg[sup -1]. min[sup -1]). Glucose disappearance was higher (P < 0.01) during the final hour of the 3.1 than 1.55 mg·kg[sup -1]·min[sup -1] id infusion (4.47 ± 0.2 vs. 2.6 ± 0.1 mg·kg[sup -1]·min[sup -1]), likely because of the slightly, but not significantly, higher glucose and insulin concentrations. We conclude that, in contrast to mice, selective portal glucose delivery at rates approximating EGP does not cause hypoglycemia in humans. [ABSTRACT FROM AUTHOR]

Presents a study that examined the effect of enteral delivery of glucose on splanchnic glucose metabolism. Assessment of concentrations of glucose, insulin and C-peptide; Measurement of the rates of intravenous and intraduodenal glucose infusion; Analysis of endogenous glucose production and glucose disappearance.

Examines whether type 2 diabetes mellitus alters systemic and regional free fatty acid metabolism. Correlation between abdominal fat compartments and systemic palmitate release; Controversy regarding insulin's effect on antilipolysis in type 2 diabetes; Markers associated with abdominal visceral fat content.

Studies the impact of the lack of suppression of glucagon on glucose tolerance in humans. Plasma insulin, glucagon, C-peptide, and growth hormone concentrations; Endogenous glucose production; Rates of endogenous glucose production during either diabetic and nondiabetic insulin profiles.

Numerous studies have used the dual-tracer method to assess postprandial glucose metabolism. The present experiments were undertaken to determine whether the marked tracer nonsteady state that occurs with the dual-tracer approach after food ingestion introduces error when it is used to simultaneously measure both meal glucose appearance (R(a meal)) and endogenous glucose production (EGP). To do so, a novel triple-tracer approach was designed: 12 subjects ingested a mixed meal containing [1-(13)C]glucose while [6-(3)H]glucose and [6,6-(2)H(2)]glucose were infused intravenously in patterns that minimized the change in the plasma ratios of [6-(3)H]glucose to [1-(13)C]glucose and of [6,6-(2)H(2)]glucose to endogenous glucose, respectively. R(a meal) and EGP measured with this approach were essentially model independent, since non-steady-state error was minimized by the protocol. Initial splanchnic glucose extraction (ISE) was 12.9% +/- 3.4%, and suppression of EGP (EGPS) was 40.3% +/- 4.1%. In contrast, when calculated with the dual-tracer one-compartment model, ISE was higher (P < 0.05) and EGPS was lower (P < 0.005) than observed with the triple-tracer approach. These errors could only be prevented by using time-varying volumes different for R(a meal) and EGP. Analysis of the dual-tracer data with a two-compartment model reduced but did not totally avoid the problems associated with marked postprandial changes in the tracer-to-tracee ratios. We conclude that results from previous studies that have used the dual-tracer one-compartment model to measure postprandial carbohydrate metabolism need to be reevaluated and that the triple-tracer technique may provide a useful approach for doing so.