Enteral infusion of glucose at rates approximating EGP enhances glucose disposal but does not cause hypoglycemia

2003 ◽  
Vol 285 (2) ◽  
pp. E280-E286 ◽  
Author(s):  
Farhad Zangeneh ◽  
Rita Basu ◽  
Pankaj Shah ◽  
Puneet Arora ◽  
Michael Camilleri ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Glucose Sensor ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Glucose Disposal ◽  
Wild Type ◽  
Glucose Disappearance ◽  
Endogenous Glucose ◽  
Glucose Plasma ◽  
Portal Infusion

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-1 · min-1 ( n = 5), 1.55 mg · kg-1 · min-1 ( n = 9), or 0/0.1 mg · kg-1 · min-1 ( n = 9) for 7 h in healthy nondiabetic subjects. [6,6-2H2]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-1 · min-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-1 · min-1 id infusions. In contrast, insulin increased ( P < 0.05) during the 1.55 and 3.0 mg · kg-1 · min-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-1 · min-1). Glucose disappearance was higher ( P < 0.01) during the final hour of the 3.1 than 1.55 mg · kg-1 · min-1 id infusion (4.47 ± 0.2 vs. 2.6 ± 0.1 mg · kg-1 · min-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.

Suppression of glucose production by GLP-1 independent of islet hormones: a novel extrapancreatic effect

2003 ◽  
Vol 285 (4) ◽  
pp. E701-E707 ◽  
Author(s):  
Ronald L. Prigeon ◽  
Shaista Quddusi ◽  
Breay Paty ◽  
David A. D'Alessio
Keyword(s):  
Plasma Glucose ◽  
Hormone Secretion ◽  
Glucose Production ◽  
Preliminary Evidence ◽  
Endogenous Glucose Production ◽  
Glucose Disposal ◽  
Islet Hormones ◽  
Islet Hormone ◽  
Endogenous Glucose ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1) is an intestinal hormone that stimulates insulin secretion and decreases glucagon release. It has been hypothesized that GLP-1 also reduces glycemia independent of its effect on islet hormones. Based on preliminary evidence that GLP-1 has independent actions on endogenous glucose production, we undertook a series of experiments that were optimized to address this question. The effect of GLP-1 on glucose appearance (Ra) and glucose disposal (Rd) was measured in eight men during a pancreatic clamp that was performed by infusing octreotide to suppress secretion of islet hormones, while insulin and glucagon were infused at rates adjusted to maintain blood glucose near fasting levels. After stabilization of plasma glucose and equilibration of [3H]glucose tracer, GLP-1 was given intravenously for 60 min. Concentrations of insulin, C-peptide, and glucagon were similar before and during the GLP-1 infusion (115 ± 14 vs. 113 ± 11 pM; 0.153 ± 0.029 vs. 0.156 ± 0.026 nM; and 64.7 ± 11.5 vs. 65.8 ± 13.8 ng/l, respectively). With the initiation of GLP-1, plasma glucose decreased in all eight subjects from steady-state levels of 4.8 ± 0.2 to a nadir of 4.1 ± 0.2 mM. This decrease in plasma glucose was accounted for by a significant 17% decrease in Ra, from 22.6 ± 2.8 to 19.1 ± 2.8 μmol · kg–1 · min–1 ( P < 0.04), with no significant change in Rd. These findings indicate that, under fasting conditions, GLP-1 decreases endogenous glucose production independent of its actions on islet hormone secretion.

246-OR: Contribution of Plasma Glucose and Hormones to the Acute Compensatory Rise in Endogenous Glucose Production (EGP) during Glucosuria in T2D Patients

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 246-OR
Author(s):  
MARIAM ALATRACH ◽  
CHRISTINA AGYIN ◽  
NITCHAKARN LAICHUTHAI ◽  
JOHN M. ADAMS ◽  
MUHAMMAD ABDUL-GHANI ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Endogenous Glucose

Acute inhibition of lipolysis does not affect postprandial suppression of endogenous glucose production

2005 ◽  
Vol 289 (6) ◽  
pp. E941-E947 ◽  
Author(s):  
Peter E. Carey ◽  
Jean Gerrard ◽  
Gary W. Cline ◽  
Chiara Dalla Man ◽  
Philip T. English ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Glucose Homeostasis ◽  
Plasma Glucose ◽  
Peak Plasma ◽  
Serum Insulin ◽  
Glucose Production ◽  
Significant Negative Correlation ◽  
Endogenous Glucose Production ◽  
Liver Fat ◽  
Endogenous Glucose

To test the hypothesis that intrahepatic availability of fatty acid could modify the rate of suppression of endogenous glucose production (EGP), acipimox or placebo was administered before and during a test meal. We used a modified isotopic methodology to measure EGP in 11 healthy subjects, and 1H magnetic resonance spectroscopic measurement of hepatic triglyceride stores was also undertaken. Acipimox suppressed plasma free fatty acids markedly before the meal (0.05 ± 0.01 mmol/l at −10 min, P = 0) and throughout the postprandial period (0.03 ± 0.01 mmol/l at 150 min). Mean peak plasma glucose was significantly lower after the meal on acipimox days (8.9 ± 0.4 vs. 10.1 ± 0.5 mmol/l, P < 0.01), as was mean peak serum insulin (653.1 ± 99.9 vs. 909 ± 118 pmol/l, P < 0.01). Fasting EGP was similar (11.15 ± 0.58 μmol·kg−1·min−1 placebo vs. 11.17 ± 0.89 mg·kg−1·min−1 acipimox). The rate of suppression of EGP after the meal was almost identical on the 2 test days (4.36 ± 1.52 vs. 3.69 ± 1.21 μmol·kg−1·min−1 at 40 min). There was a significant negative correlation between the acipimox-induced decrease in peak plasma glucose and liver triglyceride content ( r = −0.827, P = 0.002), suggesting that, when levels of liver fat were low, inhibition of lipolysis was able to affect glucose homeostasis. Acute pharmacological sequestration of fatty acids in triglyceride stores improves postprandial glucose homeostasis without effect on the immediate postprandial suppression of EGP.

Improved tolerance to sequential glucose loading (Staub-Traugott effect): size and mechanisms

2009 ◽  
Vol 297 (2) ◽  
pp. E532-E537 ◽  
Author(s):  
Sandra Bonuccelli ◽  
Elza Muscelli ◽  
Amalia Gastaldelli ◽  
Elisabetta Barsotti ◽  
Brenno D. Astiarraga ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Plasma Glucose ◽  
Cell Function ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Fat Free Mass ◽  
Oral Glucose ◽  
Glucose Response ◽  
Glucose Loading ◽  
Endogenous Glucose

Improved glucose tolerance to sequential glucose loading (Staub-Traugott effect) is an important determinant of day-to-day glycemic exposure. Its mechanisms have not been clearly established. We recruited 17 healthy volunteers to receive two sequential oral glucose tolerance tests (OGTTs), at time 0 min and 180 min ( Study I). The protocol was repeated on a separate day ( Study II) except that plasma glucose was clamped at 8.3 mmol/l between 60 and 180 min. β-Cell function was analyzed by mathematical modeling of C-peptide concentrations. In a subgroup, glucose kinetics were measured by a triple-tracer technique (infusion of [6,6-2H2]glucose and labeling of the 2 glucose loads with [1-2H]glucose and [U-13C]glucose). In both Studies I and II, the plasma glucose response to the second OGTT equaled 84 ± 2% ( P = 0.003) of the response to the first OGTT. Absolute insulin secretion was lower (37.8 ± 4.3 vs. 42.8 ± 5.1 nmol/m2, P = 0.02), but glucose potentiation (i.e., higher secretion at the same glycemia) was stronger (1.08 ± 0.02- vs. 0.92 ± 0.02-fold, P = 0.006), the increment being higher in Study II (+36 ± 5%) than Study I (+19 ± 6%, P < 0.05). In pooled data, a higher glucose area during the first OGTT was associated with a higher potentiation during the second OGTT (rho=0.60, P = 0.002). Neither insulin clearance nor glucose clearance differed between loads, and appearance of glucose over 3 h totalled 60 ± 6 g for the first load and 52 ± 5 g for the second load ( P = not significant). Fasting endogenous glucose production [13.3 ± 0.6 μmol·min−1·kg fat-free mass (FFM)−1] averaged 6.0 ± 3.8 μmol·min−1·kg FFM−1 between 0 and 180 min and 1.7 ± 2.6 between 180 and 360 min ( P < 0.03). Glucose potentiation and stronger suppression of endogenous glucose release are the main mechanisms underlying the Staub-Traugott effect.

scholarly journals Insulin action and glucose metabolism in sheep fed on dried-grass or ground, maize-based diets

1985 ◽  
Vol 54 (2) ◽  
pp. 459-471 ◽  
Author(s):  
A. N. Janes ◽  
T. E. C. Weekes ◽  
D. G. Armstrong
Keyword(s):  
Glucose Metabolism ◽  
Insulin Action ◽  
Plasma Insulin ◽  
Glucose Utilization ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
Glucose Disposal ◽  
Metabolic Clearance ◽  
Endogenous Glucose

1. The effect of an exogenous supply of glucose, provided by the digestion of maize starch in the small intestine, on endogenous glucose metabolism and insulin action was studied in sheep using the euglycaemic insulin clamp procedure.2. Insulin was infused intravenously at rates of 0.2, 0.5, 1.0 and 6.0 mU/min per kg live weight for four consecutive periods in each of four sheep fed on dried-grass and maize-based diets. Glucose was also infused intravenously at a variable rate, sufficient to maintain the plasma glucose concentration at basal levels. Whole-body rates of glucose metabolism were determined using a continuous infusion of [6-3H]glucose.3. From the resultinginsulin dose-response curves, it was observed that, when the sheep were fed on the dried-grass diet, the responsiveness of glucose metabolism to insulin was less than that reported for non-ruminants.4. When fed the maize-based diet, the glucose metabolic clearance rates (MCR) observed during insulin infusions were significantly greater (P < 0.05) than those observed for the dried-grass diet. However, after correcting for the non-insulin-mediated glucose disposal, differences between diets were not significant.5. The sensitivity of glucose utilization to insulin was not affected by diet. The plasma insulin concentrations causing half-maximal insulin-mediated glucose MCR were 103 (SE 21) and 85 (SE 11) mU/l for the dried-grass and maize-based diets respectively.6. The sensitivity of endogenous glucose production to insulin was also unaffected by diet. The plasma insulin concentrations resulting in the suppression of endogenous glucose production to half the basal level were 80 (SE 26) and 89 (SE 29) mU/l for the dried-grass and maize-based diets respectively.7. It is concluded that the observed increase in glucose utilization on the maize-based diet was due partly to a slight change in responsiveness to insulin and also partly to a change in the rate of non-insulin-mediated glucose disposal.

Glucose recycling and production in glycogenosis type I and III: stable isotope technique study

1989 ◽  
Vol 257 (3) ◽  
pp. E346-E353 ◽  
Author(s):  
B. Kalderon ◽  
S. H. Korman ◽  
A. Gutman ◽  
A. Lapidot
Keyword(s):  
Plasma Glucose ◽  
Storage Disease ◽  
Glucose Production ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Endogenous Glucose Production ◽  
Disease Type ◽  
Type I ◽  
Endogenous Glucose ◽  
Glucose Recycling

Glucose carbon recycling, endogenous glucose production, and glucose turnover rates were measured, by stable isotope methodology, in five patients with glycogen storage disease type I (GSD-I), two patients with glycogen storage disease type III (GSD-III), and three control children. A primed-constant infusion of D-[U-13C]glucose was administered nasogastrically to fasted subjects. The isotopic enrichments and 13C isotopomer distribution of plasma glucose were measured by chemical ionization gas chromatography mass spectroscopy. In response to increasing rates of glucose infusion, endogenous glucose production decreased, whereas the rate of glucose appearance or total glucose flux increased. Recycling of infused D-[U-13C]-glucose, calculated from changes in the isotopomer distribution of plasma [13C]glucose, was not detectable in GSD-I but reached 50% in GSD-III. In GSD-I the gluconeogenic pool was found to be highly labeled and recycled, whereas plasma glucose was diluted but not recycled. It is suggested that in GSD-I dilution of plasma glucose is due to release of glucose from branch points in glycogen. We propose that studies of the extent of glucose recycling and of isotopic enrichment of gluconeogenic precursors can be used as a noninvasive test for diagnosis of GSD-I and other defects in glucose production.

Peripheral and hepatic resistance to insulin and hepatic resistance to glucagon in uraemic subjects

1988 ◽  
Vol 118 (1) ◽  
pp. 125-134 ◽  
Author(s):  
Ole Schmitz
Keyword(s):  
Insulin Resistance ◽  
Insulin Infusion ◽  
Serum Insulin ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Hepatic Insulin Resistance ◽  
Glucose Disposal ◽  
Peripheral Tissues ◽  
Endogenous Glucose

Abstract. To characterize endogenous glucose production in uraemia, nondialyzed uraemic patients and controls were exposed to two major modulating hormones, insulin and glucagon. Nineteen uraemic and 15 healthy subjects underwent either a 2-step (insulin infusion rates: 0.45 and 1.0 mU·kg−1·min−1) or a 3-step (insulin infusion rates: 0.1, 0.2 and 0.3 mU·kg−1·min−1 sequential euglycaemic insulin clamp. Average steady state serum insulin concentrations were almost identical during all five infusion rates in uraemic patients (16,22, 26, 31 and 66 mU/l) and controls (15, 19, 24, 33 and 68 mU/l). At all steps, insulin infusion was accompanied by significantly lower glucose disposal rates ([3−3H]glucose) in uraemic patients compared with controls (P < 0.05 or less). Moreover, the restraining potency of insulin on endogenous glucose production was much more prominent in healthy than in uraemic subjects at the lowest three infusion rates (0.6 ± 1.0 versus 1.4 ± 0.3 (mean ± 1 sd), −0.3 ± 0.7 versus 0.7 ± 0.3, and −1.1 ± 0.7 versus 0.2 ± 0.6 mg·kg−1·min−1; P < 0.05, P < 0.01 and P < 0.01, respectively), implying a shift to the right of the dose-response curve in uraemia. In contrast, basal values were comparable (2.4 ± 0.3 versus 2.2 ± 0.6 mg·kg−1·min−1) as the difference vanished at higher infusion rates, i.e. peripheral insulinaemia above ≈30 mU/l. Another 7 uraemic patients and 7 controls were infused with glucagon at constant rates of 4 or 6 ng·kg−1·min−1, respectively, for 210 min concomitant with somatostatin (125 μg/h) and tritiated glucose. The ability of glucagon to elevate plasma glucose was markedly attenuated in uraemic patients compared with controls during the initial 60 min of glucagon exposure. This difference was entirely due to diminished hepatic glucose production (3.5 ± 0.8 versus 4.8 ± 1.0 mg·kg−1·min−1; P < 0.05). In conclusion, in addition to insulin resistance in peripheral tissues, uraemia is also associated with hepatic insulin resistance. Furthermore, glucagon challenge implies impaired early endogenous glucose release in uraemia suggesting a superimposed hepatic resistance to glucagon.

Alterations in carbohydrate metabolism in response to short-term dietary carbohydrate restriction

2005 ◽  
Vol 289 (2) ◽  
pp. E306-E312 ◽  
Author(s):  
Matthew P. Harber ◽  
Simon Schenk ◽  
Ariel L. Barkan ◽  
Jeffrey F. Horowitz
Keyword(s):  
Glucose Uptake ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Carbohydrate Oxidation ◽  
Metabolic Effects ◽  
Glucose Disposal ◽  
Carbohydrate Restriction ◽  
Dietary Carbohydrate ◽  
Endogenous Glucose ◽  
Glucose Availability

Dietary carbohydrate restriction (CR) presents a challenge to glucose homeostasis. Despite the popularity of CR diets, little is known regarding the metabolic effects of CR. The purpose of this study was to examine changes in whole body carbohydrate oxidation, glucose availability, endogenous glucose production, and peripheral glucose uptake after dietary CR, without the confounding influence of a negative energy balance. Postabsorptive rates of glucose appearance in plasma (Ra; i.e., endogenous glucose production) and disappearance from plasma (Rd; i.e., glucose uptake) were measured using isotope dilution methods after a conventional diet [60% carbohydrate (CHO), 30% fat, and 10% protein; kcals = 1.3 × resting energy expenditure (REE)] and after 2 days and 7 days of CR (5% CHO, 60% fat, and 35% protein; kcals = 1.3 × REE) in eight subjects (means ± SE; 29 ± 4 yr; BMI 24 ± 1 kg/m2) during a 9-day hospital visit. Postabsorptive plasma glucose concentration was reduced ( P = 0.01) after 2 days but returned to prediet levels the next day and remained at euglycemic levels throughout the diet (5.1 ± 0.2, 4.3 ± 0.3, and 4.8 ± 0.4 mmol/l for prediet, 2 days and 7 days, respectively). Glucose Ra and glucose Rd were reduced to below prediet levels (9.8 ± 0.6 μmol·kg−1·min−1) after 2 days of CR (7.9 ± 0.3 μmol·kg−1·min−1) and remained suppressed after 7 days (8.3 ± 0.4 μmol·kg−1·min−1; both P < 0.001). A greater suppression in carbohydrate oxidation, compared with the reduction in glucose Rd, led to an increased (all P ≤ 0.05) rate of nonoxidative glucose disposal at 7 days (5.2 ± 0.5 μmol·kg−1·min−1), compared with 2 days (2.7 ± 0.5 μmol·kg−1·min−1) and prediet (1.6 ± 0.8 μmol·kg−1·min−1). In response to eucaloric CR, a marked increase in nonoxidative glucose disposal may help maintain systemic glucose availability.

Sign in / Sign up

Export Citation Format

Share Document