Normal physical activity obliterates the deleterious effects of a high-caloric intake

2014 ◽  
Vol 116 (3) ◽  
pp. 231-239 ◽  
Author(s):  
Rikke Krogh-Madsen ◽  
Maria Pedersen ◽  
Thomas P. J. Solomon ◽  
Sine Haugaard Knudsen ◽  
Louise Seier Hansen ◽  
...  
Keyword(s):  
Physical Activity ◽  
Caloric Intake ◽  
Glucose Monitoring ◽  
Glucose Production ◽  
Study Groups ◽  
Endogenous Glucose Production ◽  
Metabolic Effects ◽  
Whole Body ◽  
Oral Glucose ◽  
Inactive Group

A high-caloric intake combined with a sedentary lifestyle is an important player in the development of type 2 diabetes mellitus (T2DM). The present study was undertaken to examine if the level of physical activity has impact on the metabolic effects of a high-caloric (+2,000 kcal/day) intake. Therefore, healthy individuals on a high-caloric intake were randomized to either 10,000 or 1,500 steps/day for 14 days. Step number, total energy expenditure, dietary records, neuropsychological tests, maximal oxygen uptake (V̇o2max), whole body dual-energy X-ray absorptiometry (DXA) and abdominal magnetic resonance imaging (MRI) scans, continuous glucose monitoring (CGM), and oral glucose tolerance tests (OGTT) with stable isotopes were performed before and after the intervention. Both study groups gained the same amount of body weight. However, the inactive group accumulated significantly more visceral fat compared with the active group. Following the 2-wk period, the inactive group also experienced a poorer glycemic control, increased endogenous glucose production, decreased hepatic insulin extraction, increased baseline plasma levels of total cholesterol and LDL, and a decreased cognitive function with regard to capacity of attention. In conclusion, we find evidence to support that habitual physical activity may prevent pathophysiological symptoms associated with diet-induced obesity.

scholarly journals Dynamic glucose disposal is driven by reduced endogenous glucose production in response to voluntary wheel running: a stable isotope approach

2020 ◽  
Vol 319 (1) ◽  
pp. E2-E10
Author(s):  
Timothy D. Allerton ◽  
Greg M. Kowalski ◽  
Hardy Hang ◽  
Jacqueline Stephens
Keyword(s):  
Stable Isotope ◽  
Wheel Running ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
Glucose Disposal ◽  
Oral Glucose ◽  
Hepatic Insulin Sensitivity ◽  
Endogenous Glucose ◽  
Voluntary Wheel

To resolve both the systems level and molecular mechanisms responsible for exercise-induced improvements in glucose tolerance, we sought to test the effect of voluntary wheel running exercise on postprandial glucose dynamics. We utilized a stable isotope-labeled oral glucose tolerance test (SI-OGTT) incorporating complementary deuterium glucose tracers at a 1:1 ratio (2-2H-glucose and 6–6 2H-glucose; 2g/kg lean body mass) to distinguish between endogenous glucose production (EGP) and whole-body glucose disposal. SI-OGTT was performed in C57BL/6J mice after 8 wk on a high-fat diet (HFD; 45% fat). Mice were then randomized to either a wheel-running cage ( n = 13, HFD Ex) or a normal cage ( n = 13, HFD Sed) while maintaining the HFD for 4 wk before performing a SI-OGTT. HFD Ex mice demonstrated improvements in whole blood glucose total area under the curve (AUC) that was attributed primarily to a reduction in EGP AUC. Serum insulin levels measured at 0 and 15 min post- glucose gavage were significantly elevated in the HFD Sed mice, whereas HFD Ex mice demonstrated the expected reduction in insulin at both time points. Overall, exercise improved hepatic insulin sensitivity by reducing postprandial EGP, but also increased whole-body glucose disposal. Finally, these results demonstrate the benefits of exercise on hepatic insulin sensitivity by combining a more physiological route of glucose administration (oral glucose) with the resolution of stable isotope tracers. These novel observations clearly demonstrate that SI-OGTT is a sensitive and cost-effective method to measure exercise adaptations in obese mice with as little as 2 µl of tail blood.

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.

Effects of treadmill exercise on fuel metabolism in hepatic cirrhosis

1991 ◽  
Vol 70 (1) ◽  
pp. 210-215 ◽  
Author(s):  
M. DeLissio ◽  
L. J. Goodyear ◽  
S. Fuller ◽  
E. L. Krawitt ◽  
J. T. Devlin
Keyword(s):  
Hepatic Cirrhosis ◽  
Treadmill Exercise ◽  
Energy Requirement ◽  
Plasma Concentrations ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
Maximal Aerobic Capacity ◽  
Control Subjects ◽  
Fuel Metabolism

We studied whole body and regional fuel metabolism before, during, and after 90 min of treadmill exercise at 50% of maximal aerobic capacity (VO2max) in four subjects with hepatic cirrhosis and in four normal volunteers. Rates of endogenous glucose production (EGP) were measured using D-[6–3H]glucose infusions and fuel oxidation using indirect calorimetry. In the basal state, cirrhotic subjects had similar rates of EGP compared with controls. Forearm release of alanine and lactate was significantly greater in cirrhotic subjects (P less than 0.05), suggesting increased basal rates of gluconeogenesis. During exercise, EGP increased 2- to 2.5-fold in control subjects (P less than 0.01) but did not increase in cirrhotic subjects. Despite lower glucose concentrations in cirrhotic subjects, progressive hypoglycemia did not occur during exercise, probably because cirrhotic subjects demonstrated increased plasma concentrations of fat-derived substrates and derived a greater percentage of total energy requirement from fat oxidation than did controls (P less than 0.05) and because forearm muscle glucose extraction was significantly lower in cirrhotic subjects compared with controls (0.5 vs. 3.6%, respectively; P less than 0.05). During recovery, control subjects demonstrated significant increases in EGP rates compared with both the basal and exercise periods, but cirrhotic subjects showed no increase. In conclusion, cirrhotic subjects failed to demonstrate the normal increase in EGP during and after exercise. Significant hypoglycemia during exercise did not occur, possibly because of the increased availability of fat-derived fuels, which may spare the requirement for circulating glucose as an oxidative fuel for exercising muscle tissues.

Insulin secretion and action and the response of endogenous glucose production to a lack of glucagon suppression in non-diabetic subjects

2021 ◽  
Author(s):  
Jon D Adams ◽  
Aoife M Egan ◽  
Marcello C Laurenti ◽  
Daniel J Schembri Wismayer ◽  
Kent R Bailey ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Action ◽  
Insulin Dose ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Oral Glucose ◽  
Prandial Insulin ◽  
Anthropometric Characteristics ◽  
Glucagon Suppression ◽  
Endogenous Glucose

Type 2 diabetes is a disease characterized by impaired insulin secretion and defective glucagon suppression in the postprandial period. We examined the effect of impaired glucagon suppression on glucose concentrations and Endogenous Glucose Production (EGP) at different degrees of insulin secretory impairment. The contribution of anthropometric characteristics, peripheral, and hepatic insulin action to this variability was also examined. To do so, we studied 54 non-diabetic subjects on two occasions in which endogenous hormone secretion was inhibited by somatostatin, with glucagon infused at a rate of 0.65 ng/kg/min, at 0 min to prevent a fall in glucagon (non-suppressed day) or at 120 min to create a transient fall in glucagon (suppressed day). Subjects received glucose (labeled with [3-3H]-glucose) infused to mimic the systemic appearance of 50g oral glucose. Insulin was infused to mimic a prandial insulin response in 18 subjects, another 18 received 80% of the dose and the remaining 18 received 60%. EGP was measured using the tracer-dilution technique. Decreased prandial insulin resulted in greater % increase in peak glucose but not in integrated glucose concentrations attributable to non-suppressed glucagon. The % change in integrated EGP was unaffected by insulin dose. Multivariate regression analysis, adjusted for age, sex, weight and insulin dose, did not show a relationship between the EGP response to impaired suppression of glucagon and insulin action as measured at the time of screening by oral glucose tolerance. A similar analysis for hepatic insulin action also did not show a relationship with the EGP response. These data indicate that the effect of impaired glucagon suppression on EGP is independent of anthropometric characteristics and insulin action.

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.

scholarly journals Mechanisms Underlying the Pathogenesis of Isolated Impaired Glucose Tolerance in Humans

2016 ◽  
Vol 101 (12) ◽  
pp. 4816-4824 ◽  
Author(s):  
Ron T. Varghese ◽  
Chiara Dalla Man ◽  
Anu Sharma ◽  
Ivan Viegas ◽  
Cristina Barosa ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Oral Glucose Tolerance Test ◽  
Glucose Tolerance Test ◽  
Fasting Glucose ◽  
Glucose Production ◽  
Tolerance Test ◽  
Endogenous Glucose Production ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Endogenous Glucose

Context: Prediabetes is a heterogeneous disorder classified on the basis of fasting glucose concentrations and 2-hour glucose tolerance. Objective: We sought to determine the relative contributions of insulin secretion and action to the pathogenesis of isolated impaired glucose tolerance (IGT). Design: The study consisted of an oral glucose tolerance test and a euglycemic clamp performed in two cohorts matched for anthropometric characteristics and fasting glucose but discordant for glucose tolerance. Setting: An inpatient clinical research unit at an academic medical center. Patients or Other Participants: Twenty-five subjects who had normal fasting glucose (NFG) and normal glucose tolerance (NGT) and 19 NFG/IGT subjects participated in this study. Intervention(s): Subjects underwent a seven-sample oral glucose tolerance test and a 4-hour euglycemic, hyperinsulinemic clamp on separate occasions. Glucose turnover during the clamp was measured using tracers, and endogenous hormone secretion was inhibited by somatostatin. Main Outcome Measures: We sought to determine whether hepatic glucose metabolism, specifically the contribution of gluconeogenesis to endogenous glucose production, differed between subjects with NFG/NGT and those with NFG/IGT. Results: Endogenous glucose production did not differ between groups before or during the clamp. Insulin-stimulated glucose disappearance was lower in NFG/IGT (24.6 ± 2.2 vs 35.0 ± 3.6 μmol/kg/min; P = .03). The disposition index was decreased in NFG/IGT (681 ± 102 vs 2231 ± 413 × 10−14 dL/kg/min2 per pmol/L; P &lt; .001). Conclusions: We conclude that innate defects in the regulation of glycogenolysis and gluconeogenesis do not contribute to NFG/IGT. However, insulin-stimulated glucose disposal is impaired, exacerbating defects in β-cell function.

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.

Potential Effects of Nonsteroidal Anti-Inflammatory Drugs in the Prevention and Treatment of Type 2 Diabetes Mellitus

2016 ◽  
Vol 30 (5) ◽  
pp. 549-556 ◽  
Author(s):  
Pamela Natalia Bellucci ◽  
María Florencia González Bagnes ◽  
Guillermo Di Girolamo ◽  
Claudio Daniel González
Keyword(s):  
Diabetes Mellitus ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Metabolic Effects ◽  
Analgesic Effects ◽  
Peripheral Insulin Resistance ◽  
Patients With Diabetes ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of heterogeneous drugs largely known for their anti-inflammatory, antipyretic, and analgesic effects, which are met by means of the inhibition of the cyclooxygenase (COX) enzymes. Even when their use in patients with diabetes mellitus is limited due to relevant adverse events, some pharmacological and metabolic effects of NSAIDs have been further studied to be potentially beneficial in the prevention and/or treatment of diabetic subjects. Effects on endogenous glucose production, peripheral insulin resistance, pancreatic islet, and systemic inflammation and the insulin clearance have been reported. In this article, we overview the scientific literature of the last 5 years regarding the potential effects of NSAID treatment on diabetes prevention/treatment. The selected papers showed information in both humans and animal models. Furthermore, we included papers that suggest new areas for further investigation, and we discussed our own suggestions on this matter.

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.

scholarly journals Long-term effects of dietary glycemic index on adiposity, energy metabolism, and physical activity in mice

2008 ◽  
Vol 295 (5) ◽  
pp. E1126-E1131 ◽  
Author(s):  
Kelly B. Scribner ◽  
Dorota B. Pawlak ◽  
Cristin M. Aubin ◽  
Joseph A. Majzoub ◽  
David S. Ludwig
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Body Composition ◽  
Energy Expenditure ◽  
Glycemic Index ◽  
Respiratory Quotient ◽  
Activity Level ◽  
Metabolic Effects ◽  
Oral Glucose

A high-glycemic index (GI) diet has been shown to increase adiposity in rodents; however, the long-term metabolic effects of a low- and high-GI diet have not been examined. In this study, a total of 48 male 129SvPas mice were fed diets high in either rapidly absorbed carbohydrate (RAC; high GI) or slowly absorbed carbohydrate (SAC; low GI) for up to 40 wk. Diets were controlled for macronutrient and micronutrient content, differing only in starch type. Body composition and insulin sensitivity were measured longitudinally by DEXA scan and oral glucose tolerance test, respectively. Food intake, respiratory quotient, physical activity, and energy expenditure were assessed using metabolic cages. Despite having similar mean body weights, mice fed the RAC diet had 40% greater body fat by the end of the study and a mean 2.2-fold greater insulin resistance compared with mice fed the SAC diet. Respiratory quotient was higher in the RAC group, indicating comparatively less fat oxidation. Although no differences in energy expenditure were observed throughout the study, total physical activity was 45% higher for the SAC-fed mice after 38 wk of feeding. We conclude that, in this animal model, 1) the effect of GI on body composition is mediated by changes in substrate oxidation, not energy intake; 2) a high-GI diet causes insulin resistance; and 3) dietary composition can affect physical activity level.

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