scholarly journals Postprandial glucose fluxes and insulin sensitivity during exercise: A study in healthy individuals

2013 ◽  
Vol 305 (4) ◽  
pp. E557-E566 ◽  
Author(s):  
Michele Schiavon ◽  
Ling Hinshaw ◽  
Ashwini Mallad ◽  
Chiara Dalla Man ◽  
Giovanni Sparacino ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Healthy Subjects ◽  
Acute Exercise ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Fat Free Mass ◽  
Glucose Turnover ◽  
Sensitivity Index ◽  
Moderate Exercise ◽  
Insulin Sensitivity Index

Quantifying the effect size of acute exercise on insulin sensitivity (SIexercise) and simultaneous measurement of glucose disappearance (Rd), endogenous glucose production (EGP), and meal glucose appearance in the postprandial state has not been developed in humans. To do so, we studied 12 healthy subjects [5 men, age 37.1 ± 3.1 yr, body mass index 24.1 ± 1.1 kg/m2, fat-free mass (FFM) 50.9 ± 3.9 kg] during moderate exercise at 50% V̇o2max for 75 min, 120–195 min after a triple-tracer mixed meal consumed at time 0. Tracer infusion rates were adjusted to achieve constant tracer-to-tracee ratio and minimize non-steady-state errors. Glucose turnover was estimated by accounting for the nonstationary kinetics introduced by exercise. Insulin sensitivity index was calculated in each subject both in the absence [time ( t) = 0–120 min, SIrest] and presence ( t = 0–360 min, SIexercise) of physical activity. EGP at t = 0 min (13.4 ± 1.1 μM·kg FFM−1·min−1) fell at t = 120 min (2.4 ± 0.4 μM·kg FFM−1·min−1) and then rapidly rose almost eightfold at t = 180 min (18.2 ± 2.6 μM·kg FFM−1·min−1) before gradually falling at t = 360 min (10.6 ± 0.9 μM·kg FFM−1·min−1). Rd rapidly peaked at t = 120 min at the start of exercise (89.5 ± 11.6 μM·kg FFM−1·min−1) and then gradually declined at t = 195 min (26.4 ± 3.3 μM·kg FFM−1·min−1) before returning to baseline at t = 360 min. SIexercise was significantly higher than SIrest (21.6 ± 3.7 vs. 12.5 ± 2.0 10−4 dl·kg−1·min−1 per μU/ml, P < 0.0005). Glucose turnover was estimated for the first time during exercise with the triple-tracer technique. Our results, applying state-of-the-art techniques, show that moderate exercise almost doubles postprandial insulin sensitivity index in healthy subjects.

scholarly journals Effect of Pramlintide on Postprandial Glucose Fluxes in Type 1 Diabetes

2016 ◽  
Vol 101 (5) ◽  
pp. 1954-1962 ◽  
Author(s):  
Ling Hinshaw ◽  
Michele Schiavon ◽  
Vikash Dadlani ◽  
Ashwini Mallad ◽  
Chiara Dalla Man ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Gastric Emptying ◽  
Insulin Sensitivity ◽  
Area Under The Curve ◽  
Postprandial Glucose ◽  
Endogenous Glucose Production ◽  
Fat Free Mass ◽  
Glucose Turnover ◽  
Plasma Glucagon

Abstract Context: Early postprandial hyperglycemia and delayed hypoglycemia remain major problems in current management of type 1 diabetes (T1D). Objective: Our objective was to investigate the effects of pramlintide, known to suppress glucagon and delay gastric emptying, on postprandial glucose fluxes in T1D. Design: This was a single-center, inpatient, randomized, crossover study. Patients: Twelve patients with T1D who completed the study were analyzed. Interventions: Subjects were studied on two occasions with or without pramlintide. Triple tracer mixed-meal method and oral minimal model were used to estimate postprandial glucose turnover and insulin sensitivity (SI). Integrated liver insulin sensitivity was calculated based on glucose turnover. Plasma glucagon and insulin were measured. Main Outcome Measure: Glucose turnover and SI were the main outcome measures. Results: With pramlintide, 2-hour postprandial glucose, insulin, glucagon, glucose turnover, and SI indices showed: plasma glucose excursions were reduced (difference in incremental area under the curve [iAUC], 444.0 mMmin, P = .0003); plasma insulin concentrations were lower (difference in iAUC, 7642.0 pMmin; P = .0099); plasma glucagon excursions were lower (difference in iAUC, 1730.6 pg/mlmin; P = .0147); meal rate of glucose appearance was lower (difference in iAUC: 1196.2 μM/kg fat free mass [FFM]; P = .0316), endogenous glucose production was not different (difference in iAUC: −105.5 μM/kg FFM; P = .5842), rate of glucose disappearance was lower (difference in iAUC: 1494.2 μM/kg FFM; P = .0083). SI and liver insulin sensitivity were not different between study visits (P &gt; .05). Conclusions: Inhibition of glucagon and gastric emptying delaying reduced 2-hour prandial glucose excursions in T1D by delaying meal rate of glucose appearance.

Epinephrine inhibits insulin-mediated glycogenesis but enhances glycolysis in human skeletal muscle

1991 ◽  
Vol 260 (3) ◽  
pp. E430-E435 ◽  
Author(s):  
I. Raz ◽  
A. Katz ◽  
M. K. Spencer
Keyword(s):  
Glycogen Synthase ◽  
Glucose Production ◽  
High Energy ◽  
Endogenous Glucose Production ◽  
Fat Free Mass ◽  
Glucose Disposal ◽  
High Energy Phosphates ◽  
Before And After ◽  
Glucose Tolerant ◽  
Femoris Muscle

The effect of epinephrine (E) infusion on insulin-mediated glucose metabolism in humans has been studied. Eight glucose-tolerant men were studied on two separate occasions: 1) during 120 min of euglycemic hyperinsulinemia (UH, approximately 5 mM; 40 mU.m-2.min-1); and 2) during UH while E was infused (UHE, 0.05 microgram.kg-1.min-1). Biopsies were taken from the quadriceps femoris muscle before and after each clamp. Glucose disposal, correcting for endogenous glucose production, was 36 +/- 3 and 18 +/- 2 (SE) mumol.kg fat-free mass (FFM)-1.min-1 during the last 40 min of UH and UHE, respectively (P less than 0.001). Nonoxidative glucose disposal (presumably glycogenesis) averaged 23.0 +/- 3.0 and 4.0 +/- 1.1 (P less than 0.001), whereas carbohydrate oxidation (which is proportional to glycolysis) averaged 13.1 +/- 1.4 and 15.3 +/- 1.1 mumol.kg FFM-1.min-1 (P less than 0.05) during UH and UHE, respectively. UHE resulted in significantly higher contents of UDP-glucose, hexose monophosphates, postphosphofructokinase intermediates, and glucose 1,6-bisphosphate (G-1,6-P2) in muscle (P less than 0.05-0.001), but there were no significant differences in high-energy phosphates or fructose 2,6-bisphosphate (F-2,6-P2) between treatments. Fractional activities of phosphorylase increased (P less than 0.01), and glycogen synthase decreased (P less than 0.001) during UHE. It is concluded that E inhibits insulin-mediated glycogenesis because of an inactivation of glycogen synthase and an activation of glycogenolysis. E also appears to inhibit insulin-mediated glucose utilization, at least partly, because of an increase in G-6-phosphate (which inhibits hexokinase) and enhances glycolysis by G-1,6-P2-, fructose 6-phosphate-, and F-1,6-P2-mediated activation of PFK.

scholarly journals Absorption and metabolism of glucose by the mesenteric-drained viscera of sheep fed on dried-grass or ground, maize-based diets

1985 ◽  
Vol 54 (2) ◽  
pp. 449-458 ◽  
Author(s):  
A. N. Janes ◽  
T. E. C. Weekes ◽  
D. G. Armstrong
Keyword(s):  
Small Intestine ◽  
Turnover Rate ◽  
Glucose Utilization ◽  
Venous Blood ◽  
Glucose Production ◽  
Glucose Absorption ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
Glucose Turnover ◽  
Total Glucose

1. Sheep fitted with re-entrant canulas in the proximal duodenum and terminal ileum were used to determine the amount of α-glucoside entering, and apparently disappearing from, the small intestine when either dried-grass or ground maize-based diets were fed. The fate of any α-glucoside entering the small intestine was studied by comparing the net disappearance of such a-glucoside from the small intestine with the absorption of glucose into the mesenteric venous blood.2. Glucose absorption from the small intestine was measured in sheep equipped with catheters in the mesenteric vein and carotid artery. A continuous infusion of [6-3H]glucose was used to determine glucose utilization by the mesenteric-drained viscera and the whole-body glucose turnover rate (GTR).3. The amounts of α-glucoside entering the small intestine when the dried-grass and maize-based diets were given were 13.9 (SE 1.5) and 95.4 (SE 16.2) g/24 h respectively; apparent digestibilities of such α-glucoside in the small intestine were 60 and 90% respectively.4. The net absorption of glucose into the mesenteric venous blood was —2.03 (SE 1.20) and 19.28 (SE 0.75) mmol/h for the dried-grass and maize-based diets respectively. Similarly, total glucose absorption amounted to 1.52 (SE 1.35) and 23.33 (SE 1.86) mmol/h (equivalent to 7 and 101 g/24 h respectively). These values represented 83 and 11 1% of the a-glucoside apparently disappearing from the small intestine, determined using the re-entrant cannulated sheep.5. Total glucose absorption represented 8 and 61% of the whole-body GTR for the dried-grass and maize-based diets respectively. Endogenous glucose production was significantly lower when the sheep were fed on the maize-based diet compared with the dried-grass diet.6. The mesenteric-drained viscera metabolized a small amount of glucose, equivalent to 234 and 17% of the total glucose absorbed for the dried-grass and maize-based diets respectively.7. It is concluded that a large proportion of the starch entering the small intestine of sheep given a maize-based diet is digested and absorbed as glucose, and thus contributes to the whole-body GTR.

Experimental validation of measurements of glucose turnover in nonsteady state.

1978 ◽  
Vol 234 (1) ◽  
pp. E84 ◽  
Author(s):  
J Radziuk ◽  
K H Norwich ◽  
M Vranic
Keyword(s):  
Dispersion Model ◽  
Glucose Production ◽  
Compartment Model ◽  
Sole Source ◽  
Volume Of Distribution ◽  
Endogenous Glucose Production ◽  
The Body ◽  
Glucose Turnover ◽  
Turnover Rates ◽  
Nonsteady State

The aim of the present experiments is to validate, in conscious dogs, the tracer infusion methods of measuring nonsteady turnover rates. This was done in nine experiments performed in four normal dogs by infusing isotopically labeled glucose (2-3H, 6-3H, 1-14C) and monitoring the concentrations of both the labeled and unlabeled substances. The validation is based on the observation that a high exogenous infusion of glucose will suppress endogenous glucose production and become the sole source of glucose in the body. By infusing glucose at a high, time-varying rate, calculating its rate of appearance, (Ra) and comparing it to the infused rate, the method can be verified. The calculations were based on: a) a single-compartment model with a modified volume of distribution; b) a two-compartment model; and c) a generalized dispersion model. The absolute values of the areas of the deviations of the calculated from the infused curves were found to be, respectively, 9.5, 8.4, and 7.8 percent of the total area under the infused curve. It was concluded that the tracer infusion method can reliably measure Ra of glucose when it is changing rapidly, and the system is out of steady state.

Regulation of glucose turnover at the onset of exercise in the dog

1992 ◽  
Vol 72 (6) ◽  
pp. 2487-2494 ◽  
Author(s):  
P. D. Miles ◽  
D. T. Finegood ◽  
H. L. Lickley ◽  
M. Vranic
Keyword(s):  
Early Period ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Molar Ratio ◽  
Glucose Turnover ◽  
Abrupt Increase ◽  
Glucoregulatory Hormones ◽  
Exercise Period ◽  
Important Regulator

The early responses of endogenous glucose production (Ra), glucose utilization (Rd), and glucoregulatory hormones to moderate treadmill exercise (12% incline, 100 m/min, 60 min) were examined in dogs. Rd increased rapidly and progressively from the start of exercise. The change in Ra, as estimated with a variable-volume model of glucose kinetics, was biphasic, with an abrupt increase by 8.5 +/- 2.3 mumol.min-1.kg-1, followed by a delayed further increase that matched Rd 11–22 min after the onset of exercise. The plasma glucagon-to-insulin molar ratio fell slightly at the onset of exercise and then increased gradually. The glucagon-to-insulin ratio was correlated with Ra over the entire exercise period (r = 0.63, P less than 0.0001), but not during the early part of exercise, when Ra increased rapidly. The catecholamine- (epinephrine plus norepinephrine) to-insulin molar ratio was correlated with Ra during the early period (r = 0.52, P less than 0.01) and over the entire period of exercise (r = 0.66, P less than 0.0001). Our results confirm previous demonstrations that the glucagon-to-insulin molar ratio is an important regulator of Ra during exercise. We hypothesize that the catecholamine-to-insulin molar ratio is important during the early period of exercise and possibly during late exercise as an additional regulatory factor to the glucagon-to-insulin molar ratio.

Effects of norepinephrine infusion on in vivo insulin sensitivity and responsiveness

1990 ◽  
Vol 259 (2) ◽  
pp. E210-E215 ◽  
Author(s):  
J. R. Lupien ◽  
M. F. Hirshman ◽  
E. S. Horton
Keyword(s):  
Insulin Sensitivity ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Glucose Disposal ◽  
Glucose Turnover ◽  
Adrenergic Blockade ◽  
Sprague Dawley ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Peripheral Tissues

The effect of a continuous infusion of norepinephrine (NE) on glucose disposal in vivo was examined in conscious restrained rats using the euglycemic-hyperinsulinemic clamp technique. NE, 1,000 micrograms.kg-1.day-1 (130 nmol.kg-1.h-1) or vehicle (CO) was infused for 10 days in adult male Sprague-Dawley rats using subcutaneously implanted osmotic minipumps. Body weight and food intake were similar in both groups of animals throughout the study. Fasting basal plasma glucose and insulin concentrations were similar in both groups. However, basal hepatic glucose production (HGP) was increased by NE treatment (9.03 +/- 0.63 vs. 13.20 +/- 1.15 mg.kg-1.min-1, P less than 0.05, CO vs. NE, respectively). Insulin infusions of 2, 6, and 200 mU.kg-1.min-1 suppressed HGP to the same degree in both groups. During 2, 6, and 200 mU.kg-1.h-1 insulin infusions the glucose disposal rate was 65, 60, and 13% greater in NE-treated animals than in controls. Acute beta-adrenergic blockade with propranolol infused at 405 nmol.kg-1.h-1 during the glucose clamps did not normalize glucose disposal. These results demonstrate that chronic NE infusion is associated with increased basal glucose turnover and increased insulin sensitivity of peripheral tissues.

Insulin sensitivity and body composition in cirrhosis: changes after TIPS

2010 ◽  
Vol 299 (2) ◽  
pp. G486-G493 ◽  
Author(s):  
Peter Holland-Fischer ◽  
Michael Festersen Nielsen ◽  
Hendrik Vilstrup ◽  
Dennis Tønner-Nielsen ◽  
Anette Mengel ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Cell Mass ◽  
Area Under The Curve ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Endogenous Glucose

Insertion of a transjugular intrahepatic porto-systemic shunt (TIPS) increases body cell mass (BCM) in patients with liver cirrhosis. The responsible mechanism is unidentified, but may involve changes in insulin sensitivity and glucose metabolism. Eleven patients with liver cirrhosis were examined before and 6 mo after a TIPS procedure with bioimpedance analyses, 2-h oral glucose tolerance tests, and two-step hyperinsulinemic euglycemic clamp with tracer-determined endogenous glucose production. After TIPS, BCM increased by 4.8 kg [confidence interval (CI): 2.7–7.3]. Fasting (f)-insulin increased from 123 ± 81 to 193 ± 124 pmol/l ( P = 0.03), whereas f-glucose was unchanged (6.0 ± 0.8 vs. 6.2 ± 1.0 mmol/l). Glucose and insulin oral glucose tolerance test area under the curve increased by 14% (CI: 7–22%) and 53% (CI: 14–90%), respectively, P < 0.05. The C-peptide-to-insulin ratio decreased by 21% (CI: 8-35%, P = 0.01). Insulin sensitivity based on glucose infusion rate (4.69 ± 1.82 vs. 4.85 ± 2.37 mg·kg−1·min−1) and glucose tracer-based rate of disappearance were unchanged (5.01 ± 1.61 vs. 4.97 ± 2.13 mg·kg−1·min−1). Despite a further increase in peripheral hyperinsulinemia, f-endogenous glucose production did not change between study days (2.01 ± 0.42 vs. 2.42 ± 0.58 mg·kg−1·min−1) and was suppressed equally by insulin (1.1 ± 0.1 vs. 1.0 ± 0.1 mg·kg−1·min−1). Insulin clearance, growth hormone, cortisol, and glucagon levels were unchanged. BCM improvement did not correlate with the measured variables. After TIPS, BCM rose, despite enhanced hyperinsulinemia and aggravated glucose intolerance, but unchanged peripheral and hepatic insulin sensitivity. This apparent discrepancy may be ascribed to shunt-related decreased insulin exposure to the liver cells. However, the anabolic effect of TIPS seems not to be related to improvements in insulin sensitivity and remains mechanistically unexplained.

Sign in / Sign up

Export Citation Format

Share Document