scholarly journals Short-term alterations in carbohydrate energy intake in humans. Striking effects on hepatic glucose production, de novo lipogenesis, lipolysis, and whole-body fuel selection.

1995 ◽  
Vol 96 (6) ◽  
pp. 2735-2743 ◽  
Author(s):  
J M Schwarz ◽  
R A Neese ◽  
S Turner ◽  
D Dare ◽  
M K Hellerstein
Keyword(s):  
Energy Intake ◽  
De Novo ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
De Novo Lipogenesis ◽  
Whole Body ◽  
Short Term ◽  
Fuel Selection ◽  
Hepatic Glucose

scholarly journals Strength exercise reduces hepatic pyruvate carboxylase and gluconeogenesis in DIO mice

2020 ◽  
Vol 247 (2) ◽  
pp. 127-138
Author(s):  
Rodrigo Martins Pereira ◽  
Kellen Cristina da Cruz Rodrigues ◽  
Marcella Ramos Sant’Ana ◽  
Guilherme Francisco Peruca ◽  
Ana Paula Morelli ◽  
...  
Keyword(s):  
Strength Training ◽  
Pyruvate Carboxylase ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Mrna Levels ◽  
Strength Exercise ◽  
Term Strength ◽  
Short Term ◽  
Hepatic Glucose ◽  
Short Term Strength

Obesity is linked to a reduction in the control of hepatic glucose production, which is the primary mechanism related to fasting hyperglycemia and the development of type 2 diabetes mellitus (T2DM). The main system involved in hepatic gluconeogenesis synthesis is controlled by pyruvate carboxylase (PC), which increases in obesity conditions. Recently, we showed that short-term strength training is an important tool against obesity-induced hyperglycemia. As aerobic exercise can reduce the hepatic PC content of obese animals, we hypothesized that strength exercise can also decrease this gluconeogenic enzyme. Therefore, this study investigated whether the metabolic benefits promoted by short-term strength training are related to changes in hepatic PC content. Swiss mice were divided into three groups: lean control (Ctl), obese sedentary (ObS), and obese short-term strength training (STST). The STST protocol was performed through one session/day for 15 days. The obese exercised animals had reduced hyperglycemia and insulin resistance. These results were related to better control of hepatic glucose production and hepatic insulin sensitivity. Our bioinformatics analysis showed that hepatic PC mRNA levels have positive correlations with glucose levels and adiposity, and negative correlations with locomotor activity and muscle mass. We also found that hepatic mRNA levels are related to lipogenic markers in the liver. Finally, we observed that the obese animals had an increased hepatic PC level; however, STST was efficient in reducing its amount. In conclusion, we provide insights into new biomolecular mechanisms by showing how STST is an efficient tool against obesity-related hyperglycemia and T2DM, even without body weight changes.

scholarly journals Importance of the route of insulin delivery to its control of glucose metabolism

2021 ◽  
Author(s):  
Dale S. Edgerton ◽  
Mary Courtney Moore ◽  
Justin M. Gregory ◽  
Guillaume Kraft ◽  
Alan D. Cherrington
Keyword(s):  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
The Body ◽  
Whole Body ◽  
Direct Effects ◽  
Pancreatic Insulin ◽  
Hepatic Glucose

Pancreatic insulin secretion produces an insulin gradient at the liver compared to the rest of the body (approximately 3:1). This physiologic distribution is lost when insulin is injected subcutaneously, causing impaired regulation of hepatic glucose production and whole body glucose uptake, as well as arterial hyperinsulinemia. Thus, the hepatoportal insulin gradient is essential to the normal control of glucose metabolism during both fasting and feeding. Insulin can regulate hepatic glucose production and uptake through multiple mechanisms, but its direct effects on the liver are dominant under physiologic conditions. Given the complications associated with iatrogenic hyperinsulinemia in patients treated with insulin, insulin designed to preferentially target the liver may have therapeutic advantages.

Effects of acute running exercise on whole body insulin action in obese male SHHF/Mcc-facp rats

1994 ◽  
Vol 77 (2) ◽  
pp. 534-541 ◽  
Author(s):  
J. Gao ◽  
W. M. Sherman ◽  
S. A. McCune ◽  
K. Osei
Keyword(s):  
Heart Failure ◽  
Insulin Sensitivity ◽  
Acute Exercise ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Whole Body ◽  
Glucose Disposal ◽  
Hepatic Glucose ◽  
Insulin Responsiveness ◽  
Obese Male

This study utilized the obese male spontaneously hypertensive heart failure rat (SHHF/Mcc-facp), which has metabolic features very similar to human non-insulin-dependent diabetes mellitus. The purpose of this study was to assess the insulin sensitivity and responsiveness of whole body glucose disposal and insulin suppressability of hepatic glucose production with use of the euglycemic-hyperinsulinemic clamp procedure in 12- to 15-wk-old SHHF/Mcc-facp rats at rest (OS) and 2.5 h after a single session of acute exercise (OE). Lean male SHHF/Mcc-facp rats were sedentary (LS) control animals. At least three clamps producing different insulin-stimulated responses were performed on each animal in a randomized order. At this age the obese animals are normotensive and have not developed congestive heart failure. Compared with LS, OS were significantly hyperglycemic and hyperinsulinemic and insulin sensitivity and responsiveness of whole body glucose uptake and insulin suppressability of hepatic glucose production were significantly decreased. Compared with LS and OS, acute exercise significantly decreased resting plasma glucose but did not alter plasma insulin. Compared with OS, acute exercise significantly increased the insulin responsiveness of whole body glucose disposal but did not affect the sensitivity of whole body glucose disposal or insulin suppressability of hepatic glucose production. Compared with LS, however, acute exercise did not “normalize” the insulin responsiveness of whole body glucose disposal. Thus a single acute exercise session improves but does not normalize whole body insulin resistance in the SHHF/Mcc-facp rat.

Adipose-specific overexpression of GLUT4 reverses insulin resistance and diabetes in mice lacking GLUT4 selectively in muscle

2005 ◽  
Vol 289 (4) ◽  
pp. E551-E561 ◽  
Author(s):  
Eugenia Carvalho ◽  
Ko Kotani ◽  
Odile D. Peroni ◽  
Barbara B. Kahn
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Transport ◽  
Fat Mass ◽  
Glucose Transporter ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Whole Body ◽  
Hepatic Glucose ◽  
Clamp Study

Adipose tissue plays an important role in glucose homeostasis and affects insulin sensitivity in other tissues. In obesity and type 2 diabetes, glucose transporter 4 (GLUT4) is downregulated in adipose tissue, and glucose transport is also impaired in muscle. To determine whether overexpression of GLUT4 selectively in adipose tissue could prevent insulin resistance when glucose transport is impaired in muscle, we bred muscle GLUT4 knockout (MG4KO) mice to mice overexpressing GLUT4 in adipose tissue (AG4Tg). Overexpression of GLUT4 in fat not only normalized the fasting hyperglycemia and glucose intolerance in MG4KO mice, but it reduced these parameters to below normal levels. Glucose infusion rate during a euglycemic clamp study was reduced 46% in MG4KO compared with controls and was restored to control levels in AG4Tg-MG4KO. Similarly, insulin action to suppress hepatic glucose production was impaired in MG4KO mice and was restored to control levels in AG4Tg-MG4KO. 2-Deoxyglucose uptake during the clamp was increased approximately twofold in white adipose tissue but remained reduced in skeletal muscle of AG4Tg-MG4KO mice. AG4Tg and AG4Tg-MG4KO mice have a slight increase in fat mass, a twofold elevation in serum free fatty acids, an ∼50% increase in serum leptin, and a 50% decrease in serum adiponectin. In MG4KO mice, serum resistin is increased 34% and GLUT4 overexpression in fat reverses this. Overexpression of GLUT4 in fat also reverses the enhanced clearance of an oral lipid load in MG4KO mice. Thus overexpression of GLUT4 in fat reverses whole body insulin resistance in MG4KO mice without restoring glucose transport in muscle. This effect occurs even though AG4Tg-MG4KO mice have increased fat mass and low adiponectin and is associated with normalization of elevated resistin levels.

scholarly journals Hepatocyte serine palmitoyl transferase 2 deficiency promotes liver C16:0-ceramide accumulation through sphingomyelin hydrolysis and leads to liver damage and dysfunction in mice

2021 ◽  
Author(s):  
Justine Lallement ◽  
Ilyès Raho ◽  
Gregory Merlen ◽  
Dominique Rainteau ◽  
Mikael Croyal ◽  
...  
Keyword(s):  
Bile Acid ◽  
Glucose Tolerance ◽  
Metabolic Disorders ◽  
De Novo ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Lipid Absorption ◽  
Compensatory Mechanism ◽  
Hepatic Glucose

Objectives: Ceramides have been shown as lipotoxic inducers, which can trigger apoptosis, inflammation and disturb numerous cell signalling pathways leading to metabolic disorders such as type 2 diabetes (T2D). In this study, we aimed to determine the role of de novo hepatic ceramide synthesis on energy and liver homeostasis in mice. Methods: In order to investigate hepatic role of de novo ceramides synthesis, we generated mice lacking serine palmitoyltransferase 2 (Sptlc2) in hepatocytes using the cre-lox system. SPTLC2 allows condensation of serine and palmitoylCoA and is the rate limiting-enzyme necessary for ceramide de novo synthesis. Sptlc2ΔHep and their littermate controls were fed with high fat diet (HFD) to induce metabolic disorders. Liver ceramides content and metabolic parameters as glucose tolerance, insulin sensitivity, and hepatic glucose production were assessed. As ceramides may have impact on bile acids (BA), we investigated BA pool composition, synthesis and transport. Finally, inflammation and apoptosis were measured in the liver using western blot analysis, pro-inflammatory cytokines expression level and immunohistochemistry. Results: Despite lower expression of hepatic Sptlc2, we observed an increased concentration of hepatic ceramides, especially C16:0-ceramide. Hepatic deletion of Sptlc2 in mice was also associated with an increased neutral sphingomyelinase 2 (nSmase2) expression, and a decreased sphingomyelin content in the liver. We showed that Sptlc2ΔHep mice are protected against body mass gain normally induced by HFD and displayed a decreased body fat mass. BA hydrophobicity was drastically decreased in Sptlc2ΔHep mice, and was associated with a defect in lipid absorption. In addition, an important increase of tauro-murocholic acid T-MCA in BA pool composition of Sptlc2ΔHep mice was associated with a downregulation of the nuclear bile acid receptor FXR target genes in ileum and liver. Sptlc2 deficiency also enhanced glucose tolerance and attenuated hepatic glucose production in an insulin-independent manner. Finally, Sptlc2 disruption promoted progressive development of hepatic fibrosis, apoptosis and inflammation in an age-related manner. Conclusion: Our data demonstrate for the first time a potential compensatory mechanism to regulate hepatic ceramides content from sphingomyelin hydrolysis. In addition, our results highlight the role of hepatic sphingolipid modulation on hepatic glucose production through bile acid composition changes.

Metabolic and thermogenic effects of lactate infusion in humans

1993 ◽  
Vol 265 (3) ◽  
pp. E504-E512 ◽  
Author(s):  
E. Ferrannini ◽  
A. Natali ◽  
L. S. Brandi ◽  
R. Bonadonna ◽  
S. V. De Kreutzemberg ◽  
...  
Keyword(s):  
Glucose Utilization ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Major Change ◽  
Sodium Lactate ◽  
Whole Body ◽  
Glucose Disposal ◽  
Experimental Conditions ◽  
Hepatic Glucose ◽  
Lactate Infusion

Lactate has been suggested to interfere with intermediary metabolism by restricting both lipolysis and glucose utilization. To test this hypothesis, in paired studies in healthy volunteers, sodium lactate (25 mumol.min-1 x kg-1) or saline was infused for 1 h in the fasting state and during 2 h of euglycemic (4.75 mM) hyperinsulinemia (approximately 400 pmol/l). Hyperlactatemia (approximately 2 mM) had no inhibitory effect on fasting free fatty acid or glycerol levels nor did it alter the suppressive action of insulin on these substrates. Likewise, sodium lactate infusion did not influence hepatic glucose production ([3-3H]glucose technique) or its suppression by insulin. During the clamp, hyperlactatemia was associated with a small increase in whole body glucose disposal (34.9 +/- 4.1 vs. 30.3 +/- 3.7 mumol.min-1 x kg-1, P < 0.05) with no major change in the pattern of substrate (carbohydrate vs. lipid) oxidation. By simultaneously measuring arteriovenous gradients across the deep tissues of the forearm (forearm technique), it was found that hyperlactatemia did not impede insulin-mediated glucose uptake; furthermore, it could be estimated that muscle tissues were responsible for the disposal of roughly one-fifth of the lactate load. Whole body energy expenditure was stimulated above the level achieved with hyperinsulinemia when lactate was also infused. Thus, under the present experimental conditions, physiological hyperlactatemia did not interfere with lipolysis, hepatic glucose production, or whole body or forearm muscle glucose utilization, or with insulin action on these processes, and was accompanied by a strong thermogenic effect.

Epinephrine-induced changes in hepatic glucose production after ethanol

1994 ◽  
Vol 266 (6) ◽  
pp. E863-E869
Author(s):  
C. H. Lang ◽  
P. E. Molina ◽  
N. Skrepnick ◽  
G. J. Bagby ◽  
J. J. Spitzer
Keyword(s):  
Glucose Metabolism ◽  
Metabolic Response ◽  
Hepatic Glucose Production ◽  
Plasma Concentrations ◽  
Plasma Catecholamines ◽  
Glucose Production ◽  
Whole Body ◽  
Metabolic Clearance ◽  
Hepatic Glucose ◽  
Acute Ethanol

Previous studies indicate that catecholamines play an important role in mediating the glucose metabolic response to endotoxin. Because acute ethanol (EtOH) intoxication impairs this response, the present study was initiated to ascertain whether EtOH attenuates the lipopolysaccharide response by decreasing the increment in plasma catecholamines after endotoxin or by decreasing the responsiveness of rats to epinephrine. All studies were performed on chronically catheterized fasted rats infused intravenously with either EtOH or an equal volume of saline. In the first series of experiments, intravenous administration of Escherichia coli endotoxin increased, to the same extent, the plasma concentrations of epinephrine and norepinephrine in both saline- and EtOH-infused rats. In the second study, rats were infused with [3-3H]glucose to assess whole body glucose metabolism and the ability of EtOH to alter the glucose metabolic response to epinephrine. The exogenous infusion of a maximally stimulating dose of epinephrine (1 microgram.min-1.kg-1) into saline-infused control animals for 3 h produced a marked hyperglycemia that resulted from a sustained increase in the rate of hepatic glucose production and a reduction in the metabolic clearance rate for glucose. EtOH infusion did not prevent the epinephrine-induced hyperglycemia but blunted the stimulatory effect of epinephrine on glucose production. The differences in glucose metabolism between saline- and EtOH-treated rats could not be explained by changes in plasma insulin or glucagon concentrations. Furthermore, the ability of EtOH to impair the epinephrine-induced increase in glucose production was still evident in rats treated with 4-methylpyrazole, an inhibitor of alcohol dehydrogenase.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Effects of dietary propionate on hepatic glucose production, whole-body glucose utilization, carbohydrate and lipid metabolism in normal rats

1995 ◽  
Vol 73 (2) ◽  
pp. 241-251 ◽  
Author(s):  
Josette Boillot ◽  
Catherine Alamowitch ◽  
Anne-Marie Berger ◽  
Jing Luo ◽  
Françoise Bruzzo ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Glucose Utilization ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Whole Body ◽  
Dietary Fibres ◽  
Carbohydrate And Lipid Metabolism ◽  
Hepatic Glucose ◽  
Anaesthetized Rats

Increased intake of dietary fibres is associated with several beneficial effects on carbohydrate and lipid metabolism. The colonic fermentation of dietary fibres produces short-chain fatty acids (SCFA; acetate, propionate and butyrate). Some authors have suggested that SCFA could be partly responsible for the effects of dietary fibres. The purpose of the present study was to test the effects of one of the SCFA, propionate. The effects of moderate amounts of dietary propionate on insulin sensitivity and hepatic glucose production were studied in male Sprague-Dawley rats. Two groups of twenty-one adult rats were fed for 3 weeks on a diet containing 78 g propionate/kg (P) or 78 g/kg of a poorly fermentable cellulose (control group; C). Feed intake, body weight, fasting plasma glucose, insulin, free fatty acids, alanine, lactate, glycerol and β-hydroxybutyrate levels were measured weekly in anaesthetized rats. At the end of the feeding period basal hepatic glucose production (BHGP) was measured with a primed continuous infusion of [3−3H]glucose and the in vivo insulin sensitivity in rats was quantified by the euglycaemic-hyperinsulinaemic clamp technique (0.6 and 2 U/kg per h). At that time fasting plasma glucose measured in anaesthetized rats was significantly lower in group P than in group C: 7·7 (SE 0·2) v. 8.5 (SE 0·2) mmol/l respectively (P < 0·002); plasma insulin levels were not significantly different. Neither the BHGP (mg/min per kg; C 14·8 (SE 1·3), P 15·1 (SE 1·3); n 7, not significant) nor the basal metabolic clearance (ml/min per kg; 8·9 (SE 08) v. 9·9 (SE 1·1); not significant) were different between treatments. Hepatic glucose production and glucose utilization at the two insulin concentrations (approximately 500 and 1500 mU/l respectively, n 7) did not differ significantly between the two groups. These results show that dietary propionate chronically ingested by normal rats could decrease fasting glycaemia, but from our findings, no effect on hepatic glucose production and whole-body glucose utilization could be clearly demonstrated.

scholarly journals Hepatic insulin resistance and increased hepatic glucose production in mice lacking Fgf21

2015 ◽  
Vol 226 (3) ◽  
pp. 207-217 ◽  
Author(s):  
João Paulo G Camporez ◽  
Mohamed Asrih ◽  
Dongyan Zhang ◽  
Mario Kahn ◽  
Varman T Samuel ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Hepatic Insulin Resistance ◽  
Whole Body ◽  
Fibroblast Growth Factor 21 ◽  
Glucose And Lipid Metabolism ◽  
Hepatic Glucose

Fibroblast growth factor 21 (FGF21) is an important regulator of hepatic glucose and lipid metabolism and represents a potential pharmacological agent for the treatment of type 2 diabetes and obesity. Mice fed a ketogenic diet (KD) develop hepatic insulin resistance in association with high levels of FGF21, suggesting a state of FGF21 resistance. To address the role of FGF21 in hepatic insulin resistance, we assessed insulin action in FGF21 whole-body knock-out (FGF21 KO) male mice and their littermate WT controls fed a KD. Here, we report that FGF21 KO mice have hepatic insulin resistance and increased hepatic glucose production associated with an increase in plasma glucagon levels. FGF21 KO mice are also hypometabolic and display increased fat mass compared with their WT littermates. Taken together, these findings support a major role of FGF21 in regulating energy expenditure and hepatic glucose and lipid metabolism, and its potential role as a candidate in the treatment of diseases associated with insulin resistance.

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