Effects of high-fat diet and exercise training on intracellular glucose metabolism in rats

2000 ◽  
Vol 278 (6) ◽  
pp. E977-E984 ◽  
Author(s):  
Chul-Hee Kim ◽  
Jang H. Youn ◽  
Joong-Yeol Park ◽  
Sung K. Hong ◽  
Kyong S. Park ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Exercise Training ◽  
Glucose Uptake ◽  
Protein Content ◽  
High Fat Diet ◽  
Glycogen Synthesis ◽  
Whole Body ◽  
High Fat ◽  
Glut 4 ◽  
Intracellular Glucose

We examined the effects of high-fat diet (HFD) and exercise training on insulin-stimulated whole body glucose fluxes and several key steps of glucose metabolism in skeletal muscle. Rats were maintained for 3 wk on either low-fat (LFD) or high-fat diet with or without exercise training (swimming for 3 h per day). After the 3-wk diet/exercise treatments, animals underwent hyperinsulinemic euglycemic clamp experiments for measurements of insulin-stimulated whole body glucose fluxes. In addition, muscle samples were taken at the end of the clamps for measurements of glucose 6-phosphate (G-6- P) and GLUT-4 protein contents, hexokinase, and glycogen synthase (GS) activities. Insulin-stimulated glucose uptake was decreased by HFD and increased by exercise training ( P < 0.01 for both). The opposite effects of HFD and exercise training on insulin-stimulated glucose uptake were associated with similar increases in muscle G-6- P levels ( P < 0.05 for both). However, the increase in G-6- Plevel was accompanied by decreased GS activity without changes in GLUT-4 protein content and hexokinase activities in the HFD group. In contrast, the increase in G-6- P level in the exercise-trained group was accompanied by increased GLUT-4 protein content and hexokinase II (cytosolic) and GS activities. These results suggest that HFD and exercise training affect insulin sensitivity by acting predominantly on different steps of intracellular glucose metabolism. High-fat feeding appears to induce insulin resistance by affecting predominantly steps distal to G-6- P (e.g., glycolysis and glycogen synthesis). Exercise training affected multiple steps of glucose metabolism both proximal and distal to G-6- P. However, increased muscle G-6- P levels in the face of increased glucose metabolic fluxes suggest that the effect of exercise training is quantitatively more prominent on the steps proximal to G-6- P(i.e., glucose transport and phosphorylation).

Prolonged suppression of glucose metabolism causes insulin resistance in rat skeletal muscle

1997 ◽  
Vol 272 (2) ◽  
pp. E288-E296 ◽  
Author(s):  
J. K. Kim ◽  
J. H. Youn
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Skeletal Muscles ◽  
Glycogen Synthesis ◽  
Whole Body ◽  
Metabolic Fluxes ◽  
Phosphate Inhibition ◽  
Intracellular Glucose

To determine whether an impairment of intracellular glucose metabolism causes insulin resistance, we examined the effects of suppression of glycolysis or glycogen synthesis on whole body and skeletal muscle insulin-stimulated glucose uptake during 450-min hyperinsulinemic euglycemic clamps in conscious rats. After the initial 150 min to attain steady-state insulin action, animals received an additional infusion of saline, Intralipid and heparin (to suppress glycolysis), or amylin (to suppress glycogen synthesis) for up to 300 min. Insulin-stimulated whole body glucose fluxes were constant with saline infusion (n = 7). In contrast, Intralipid infusion (n = 7) suppressed glycolysis by approximately 32%, and amylin infusion (n = 7) suppressed glycogen synthesis by approximately 45% within 30 min after the start of the infusions (P < 0.05). The suppression of metabolic fluxes increased muscle glucose 6-phosphate levels (P < 0.05), but this did not immediately affect insulin-stimulated glucose uptake due to compensatory increases in other metabolic fluxes. Insulin-stimulated whole body glucose uptake started to decrease at approximately 60 min and was significantly decreased by approximately 30% at the end of clamps (P < 0.05). Similar patterns of changes in insulin-stimulated glucose fluxes were observed in individual skeletal muscles. Thus the suppression of intracellular glucose metabolism caused decreases in insulin-stimulated glucose uptake through a cellular adaptive mechanism in response to a prolonged elevation of glucose 6-phosphate rather than the classic mechanism involving glucose 6-phosphate inhibition of hexokinase.

scholarly journals Resveratrol Ameliorates High-Fat-Diet-Induced Abnormalities in Hepatic Glucose Metabolism in Mice via the AMP-Activated Protein Kinase Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Caiping Lu ◽  
Hanying Xing ◽  
Linquan Yang ◽  
Kaiting Chen ◽  
Linyi Shu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Protein Kinase ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
High Fat Diet ◽  
Blood Glucose Concentration ◽  
Glycogen Synthesis ◽  
Liver Fat ◽  
High Fat ◽  
Amp Activated Protein Kinase

Diabetes mellitus is highly prevalent worldwide. High-fat-diet (HFD) consumption can lead to liver fat accumulation, impair hepatic glycometabolism, and cause insulin resistance and the development of diabetes. Resveratrol has been shown to improve the blood glucose concentration of diabetic mice, but its effect on the abnormal hepatic glycometabolism induced by HFD-feeding and the mechanism involved are unknown. In this study, we determined the effects of resveratrol on the insulin resistance of high-fat-diet-fed mice and a hepatocyte model by measuring serum biochemical indexes, key indicators of glycometabolism, glucose uptake, and glycogen synthesis in hepatocytes. We found that resveratrol treatment significantly ameliorated the HFD-induced abnormalities in glucose metabolism in mice, increased glucose absorption and glycogen synthesis, downregulated protein phosphatase 2A (PP2A) and activated Ca2+/CaM-dependent protein kinase kinase β (CaMKKβ), and increased the phosphorylation of AMP-activated protein kinase (AMPK). In insulin-resistant HepG2 cells, the administration of a PP2A activator or CaMKKβ inhibitor attenuated the effects of resveratrol, but the administration of an AMPK inhibitor abolished the effects of resveratrol. Resveratrol significantly ameliorates abnormalities in glycometabolism induced by HFD-feeding and increases glucose uptake and glycogen synthesis in hepatocytes. These effects are mediated through the activation of AMPK by PP2A and CaMKKβ.

Time course of insulin resistance associated with feeding dogs a high-fat diet

1997 ◽  
Vol 272 (1) ◽  
pp. E147-E154 ◽  
Author(s):  
A. P. Rocchini ◽  
P. Marker ◽  
T. Cervenka
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Glucose Uptake ◽  
Dose Response ◽  
High Fat Diet ◽  
Time Course ◽  
Rapid Development ◽  
Diet Group ◽  
Whole Body ◽  
High Fat

The current study evaluated both the time course of insulin resistance associated with feeding dogs a high-fat diet and the relationship between the development of insulin resistance and the increase in blood pressure that also occurs. Twelve adult mongrel dogs were chronically instrumented and randomly assigned to either a control diet group (n = 4) or a high-fat diet group (n = 8). Insulin resistance was assessed by a weekly, single-dose (2 mU.kg-1.min-1) euglycemic-hyperinsulinemic clamp on all dogs. Feeding dogs a high-fat diet was associated with a 3.7 +/- 0.5 kg increase in body weight, a 20 +/- 4 mmHg increase in mean blood pressure, a reduction in insulin-mediated glucose uptake [(in mumol-kg-1.min-1) decreasing from 72 +/- 6 before to 49 +/- 7 at 1 wk, 29 +/- 3 at 3 wk, and 30 +/- 2 at 6 wk of the high-fat diet, P < 0.01]. and a reduced insulin-mediated increase in cardiac output. In eight dogs (4 high fat and 4 control), the dose-response relationship of insulin-induced glucose uptake also was studied. The whole body glucose uptake dose-response curve was shifted to the right, and the rate of maximal whole body glucose uptake was significantly decreased (P < 0.001). Finally, we observed a direct relationship between the high-fat diet-induced weekly increase in mean arterial pressure and the degree to which insulin resistance developed. In summary, the current study documents that feeding dogs a high-fat diet causes the rapid development of insulin resistance that is the result of both a reduced sensitivity and a reduced responsiveness to insulin.

Abstract 15813: Loss-of-Function Mutation in Toll-Like Receptor 4 Partially Protects Against Peripheral and Cardiac Insulin Resistance During a Long-Term High-Fat Diet

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Ellen Jackson ◽  
Elizabeth Rendina-Ruedy ◽  
Matt Priest ◽  
Brenda Smith ◽  
Veronique Lacombe
Keyword(s):  
Insulin Resistance ◽  
Protein Content ◽  
Glucose Transport ◽  
High Fat Diet ◽  
Whole Body ◽  
Toll Like Receptor ◽  
Loss Of Function ◽  
High Fat ◽  
The Face ◽  
Tlr4 Activation

Diabetes mellitus is an epidemic disease characterized by alterations in glucose transport, which is tightly regulated by a family of specialized proteins called the glucose transporters (GLUTs). Although diabetic cardiomyopathy is a common complication in diabetic patients, its pathogenesis is still not well understood. Toll-like receptor (TLR) 4, which plays a central role in pathogen recognition by the innate immune system, may also play a critical role in linking inflammation and metabolic disease. We hypothesized that TLR4 activation triggers cardiac insulin resistance. We used mice with a loss-of function mutation in TLR4 (C3H/HeJ) and age-matched wild-type (WT, C57BL/6N) mice (n=8/group) to investigate how feeding a high-fat diet (HFD, 60% kcal from fat) for 16 weeks affected whole-body and cardiac glucose metabolism. After 16 weeks, WT mice fed a HFD were obese and developed hyperglycemia and insulin resistance compared to WT mice on a control diet (10% kcal from fat). The C3H/HeJ mice were partially protected against HFD-induced obesity and insulin resistance. In the heart, WT mice fed a HFD had a 30% decrease (P<0.05) in GLUT4 protein content as measured by Western Blot of cardiac crude membrane protein extracts. In contrast, the loss-of-function point mutation in TLR4 partially rescued cardiac GLUT4 content in the face of a HFD. Interestingly, there was a 40% increase (P<0.05) in the novel GLUT isoform, GLUT8, in the heart when mice of either genotype were fed a HFD. Additionally, GLUT4 protein content was negatively (P<0.05) correlated with GLUT8 content in the myocardium, suggesting that GLUT8 may act as a compensatory mechanism in the face of HFD-induced GLUT4 downregulation. Phosphorylated Akt, a key protein of the insulin signaling pathway, was positively (P<0.05) correlated with GLUT4 content, while the basal/inactive form was negatively correlated. In conclusion, these data suggest that activation of TLR4 activation during diabetes and obesity alters glucose transport by an Akt mechanism, and as such is a pathogenic factor during peripheral and cardiac insulin resistance. Overall, TLR4 appears to be a key modulator in the cross-talk between inflammatory and metabolic pathways, as well as a potential therapeutic target for diabetes.

Exercise training prevents the development of cardiac dysfunction in the low-dose streptozotocin diabetic rats fed a high-fat diet

2013 ◽  
Vol 91 (1) ◽  
pp. 80-89 ◽  
Author(s):  
Riley A. Epp ◽  
Shanel E. Susser ◽  
Marc P. Morissette ◽  
D. Scott Kehler ◽  
Davinder S. Jassal ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Exercise Training ◽  
Protein Content ◽  
Cardiac Dysfunction ◽  
High Fat Diet ◽  
Low Dose ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
High Fat ◽  
Altered Expression

This study tested the hypothesis that exercise training would prevent the development of diabetes-induced cardiac dysfunction and altered expression of sarcoplasmic reticulum Ca2 +-transport proteins in the low-dose streptozotocin-induced diabetic rats fed a high-fat diet (HFD+STZ). Male Sprague–Dawley rats (4 weeks old; 125–150 g) were made diabetic using a high-fat diet (40% fat, w/w) and a low-dose of streptozotocin (35 mg·(kg body mass)–1) by intravenous injection. Diabetic animals were divided among a sedentary group (Sed+HFD+STZ) or an exercise-trained group (Ex+HFD+STZ) that accumulated 3554 ± 338 m·day–1 of voluntary wheel running (mean ± SE). Sedentary animals fed a low-fat diet served as the control (Sed+LFD). Oral glucose tolerance was impaired in the sedentary diabetic group (1179 ± 29; area under the curve (a.u.c.)) compared with that in the sedentary control animals (1447 ± 42 a.u.c.). Although left ventricular systolic function was unchanged by diabetes, impaired E/A ratios (i.e., diastolic function) and rates of pressure decay (–dP/dt) indicated the presence of diastolic dysfunction. Diabetes also reduced SERCA2a protein content and maximal SERCA2a activity (Vmax) by 21% and 32%, respectively. In contrast, the change in each parameter was attenuated by exercise training. Based on these data, it appears that exercise training prevented the development of diabetic cardiomyopathy and the dysregulation of sarcoplasmic reticulum protein content in an inducible animal model of type 2 diabetes.

scholarly journals Urtica dioica Whole Vegetable as a Functional Food Targeting Fat Accumulation and Insulin Resistance-a Preliminary Study in a Mouse Pre-Diabetic Model

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1059
Author(s):  
Si Fan ◽  
Samnhita Raychaudhuri ◽  
Olivia Kraus ◽  
Md Shahinozzaman ◽  
Leila Lofti ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Glucose Metabolism ◽  
High Fat Diet ◽  
Urtica Dioica ◽  
Whole Body ◽  
High Fat ◽  
Fat Accumulation ◽  
Diet Induced Obesity

The shoot of Urtica dioica is used in several cultures as a vegetable or herb. However, not much has been studied about the potential of this plant when consumed as a whole food/vegetable rather than an extract for dietary supplements. In a 12-week dietary intervention study, we tested the effect of U. dioica vegetable on high fat diet induced obesity and insulin resistance in C57BL/6J mice. Mice were fed ad libitum with isocaloric diets containing 10% fat or 45% fat with or without U. dioica. The diet supplemented with U. dioica attenuated high fat diet induced weight gain (p < 0.005; n = 9), fat accumulation in adipose tissue (p < 0.005; n = 9), and whole-body insulin resistance (HOMA-IR index) (p < 0.001; n = 9). Analysis of gene expression in skeletal muscle showed no effect on the constituents of the insulin signaling pathway (AKT, IRS proteins, PI3K, GLUT4, and insulin receptor). Notable genes that impact lipid or glucose metabolism and whose expression was changed by U. dioica include fasting induced adipocyte factor (FIAF) in adipose and skeletal muscle, peroxisome proliferator-activated receptor-α (Ppar-α) and forkhead box protein (FOXO1) in muscle and liver, and Carnitine palmitoyltransferase I (Cpt1) in liver (p < 0.01). We conclude that U. dioica vegetable protects against diet induced obesity through mechanisms involving lipid accumulation and glucose metabolism in skeletal muscle, liver, and adipose tissue.

Effects of exercise training on skeletal muscle glucose uptake and transport

1993 ◽  
Vol 264 (3) ◽  
pp. C727-C733 ◽  
Author(s):  
G. J. Etgen ◽  
J. T. Brozinick ◽  
H. Y. Kang ◽  
J. L. Ivy
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Glucose Uptake ◽  
Protein Content ◽  
Glucose Transport ◽  
Exercise Session ◽  
Rat Skeletal Muscle ◽  
Glut 4 ◽  
Skeletal Muscle Glucose Uptake ◽  
Uptake And Transport

Exercise training increases the concentration of GLUT-4 protein in skeletal muscle that is associated with an increase in maximal insulin-stimulated glucose transport. The purpose of this study was to determine whether exercise training results in a long-lasting increase in insulin-stimulated glucose transport in rat skeletal muscle. Glucose uptake and skeletal muscle 3-O-methyl-D-glucose (3-MG) transport were determined during hindlimb perfusion in the presence of a maximally stimulating concentration of insulin (10 mU/ml). Hindlimb glucose uptake was approximately 29% above sedentary (Sed) levels in rats examined within 24 h (24H) of their last exercise session. However, when rats were examined 48 h (48H) after their last exercise session, hindlimb glucose uptake was not different from Sed levels. Maximal 3-MG transport was enhanced, above Sed levels, in red (RG; 72% increase) and white (WG; 44% increase) gastrocnemius and plantaris (Plan; 67% increase) muscles, but not soleus (Sol), of 24H rats. GLUT-4 protein content was significantly elevated in those muscles that exhibited enhanced 3-MG transport in 24H rats. GLUT-4 protein content was also elevated in RG, WG, and Plan of 48H rats and was not different from 24H rats. Despite the elevated GLUT-4 protein content, 3-MG transport in 48H rats was only slightly, although statistically not significantly, higher than in Sed rats. These results provide evidence that exercise training does not result in a persistent increase in skeletal muscle glucose uptake or transport, despite an increase in GLUT-4 protein content.

scholarly journals Adrenaline responsiveness of glucose metabolism in insulin-resistant adipose tissue of rats fed a high-fat diet

1979 ◽  
Vol 180 (2) ◽  
pp. 431-433 ◽  
Author(s):  
C Susini ◽  
M Lavau ◽  
J Herzog
Keyword(s):  
Adipose Tissue ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
High Fat Diet ◽  
Glucose Utilization ◽  
High Fat ◽  
Glycerol Moiety ◽  
Insulin Resistant ◽  
The One ◽  
Fat Pads

The effects of adrenaline (0.5 microM) and the combination of adrenaline and insulin (1.7nM) on [6-14C]glucose metabolism were assessed in epididymal fat-pads from rats fed either a low- or high-fat diet. The response of lipolysis to adrenaline was clearly diminished in fat-fed rats. Insulin added to adrenaline inhibited the lipolysis by 50% regardless of the diet. Glucose utilization in adipose tissue of fat-fed rats was markedly stimulated by adrenaline (glucose uptake was increased 3-fold and the production of CO2 and the glycerol moiety of acylglycerol was increased 4-fold). However, adipose tissue from fat-fed rats was resistant to the effect of insulin to produce a further increase in adrenaline-stimulated glucose uptake. The intracellular capacity of lipogenesis on the one hand, and the production of CO2 and the glycerol moiety of acylglycerol on the other, are of prime importance in the action of insulin and adrenaline on glucose utilization in this model.

Energy balance and diabetes. The effects of cold exposure, exercise training, and diet composition on glucose tolerance and glucose metabolism in rat peripheral tissues

1989 ◽  
Vol 67 (4) ◽  
pp. 382-393 ◽  
Author(s):  
Ludwik Jan Bukowiecki
Keyword(s):  
Insulin Resistance ◽  
Glucose Metabolism ◽  
Energy Expenditure ◽  
Exercise Training ◽  
Glucose Tolerance ◽  
Glucose Uptake ◽  
Cold Exposure ◽  
High Fat ◽  
Peripheral Tissues ◽  
Brown Adipose

The effects of cold exposure, exercise training, and diet (high fat versus high carbohydrate) on glucose tolerance and glucose metabolism in rat peripheral tissues will be briefly reviewed. Stimulation of energy expenditure by cold exposure (4 °C) or exercise training generally leads to decreased plasma insulin levels and to an improvement in glucose tolerance, suggesting that insulin action on peripheral tissues is increased when energy expenditure is stimulated. On the contrary, feeding high-fat diets to sedentary rats living in the warm (25 °C) induces hyperinsulinemia and insulin resistance resulting in a marked deterioration of glucose tolerance. Nevertheless, cold exposure reverses the diabetogenic effects of high-fat feeding, demonstrating that nutrition-induced insulin resistance is amplified in sedentary animals living at temperatures close to thermoneutrality. Radioactive tracer studies of 2-deoxyglucose uptake in peripheral tissues revealed that cold exposure synergistically potentiates the effects of insulin on glucose uptake in skeletal muscles as well as in white and brown adipose tissues. However, more recent data showed that cold exposure improves glucose tolerance and stimulates glucose uptake in starved animals (ie., in the virtual absence of circulating insulin) nearly by the same order of magnitude as in fed animals. It is therefore concluded that cold exposure, and possibly also exercise, improve glucose tolerance and stimulate glucose uptake in peripheral tissues primarily by enhancing glucose oxidation via insulin-independent pathways, and secondarily by increasing the responsiveness of peripheral tissues to insulin.Key words: insulin, brown adipose tissue, skeletal muscle, 2-deoxyglucose, diabetes.

scholarly journals Osteoblastic glucocorticoid signaling exacerbates high-fat-diet- induced bone loss and obesity

Bone Research ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Sarah Kim ◽  
Holger Henneicke ◽  
Lauryn L. Cavanagh ◽  
Eugenie Macfarlane ◽  
Lee Joanne Thai ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Bone Loss ◽  
Bone Formation ◽  
Glucose Uptake ◽  
High Fat Diet ◽  
Metabolic Response ◽  
Whole Body ◽  
Wild Type ◽  
High Fat ◽  
Glucocorticoid Signaling

AbstractChronic high-fat diet (HFD) consumption not only promotes obesity and insulin resistance, but also causes bone loss through mechanisms that are not well understood. Here, we fed wild-type CD-1 mice either chow or a HFD (43% of energy from fat) for 18 weeks; HFD-fed mice exhibited decreased trabecular volume (−28%) and cortical thickness (−14%) compared to chow-fed mice. In HFD-fed mice, bone loss was due to reduced bone formation and mineral apposition, without obvious effects on bone resorption. HFD feeding also increased skeletal expression of sclerostin and caused deterioration of the osteocyte lacunocanalicular network (LCN). In mice fed HFD, skeletal glucocorticoid signaling was activated relative to chow-fed mice, independent of serum corticosterone concentrations. We therefore examined whether skeletal glucocorticoid signaling was necessary for HFD-induced bone loss, using transgenic mice lacking glucocorticoid signaling in osteoblasts and osteocytes (HSD2OB/OCY-tg mice). In HSD2OB/OCY-tg mice, bone formation and mineral apposition rates were not suppressed by HFD, and bone loss was significantly attenuated. Interestingly, in HSD2OB/OCY-tg mice fed HFD, both Wnt signaling (less sclerostin induction, increased β-catenin expression) and glucose uptake were significantly increased, relative to diet- and genotype-matched controls. The osteocyte LCN remained intact in HFD-fed HSD2OB/OCY-tg mice. When fed a HFD, HSD2OB/OCY-tg mice also increased their energy expenditure and were protected against obesity, insulin resistance, and dyslipidemia. Therefore, glucocorticoid signaling in osteoblasts and osteocytes contributes to the suppression of bone formation in HFD-fed mice. Skeletal glucocorticoid signaling is also an important determinant of glucose uptake in bone, which influences the whole-body metabolic response to HFD.

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