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.

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.

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.

Hepatic glucose production and insulin sensitivity and responsiveness in iron-deficient anemic rats

1993 ◽  
Vol 264 (3) ◽  
pp. E380-E390 ◽  
Author(s):  
M. J. Borel ◽  
J. L. Beard ◽  
P. A. Farrell
Keyword(s):  
Insulin Sensitivity ◽  
Hepatic Glucose Production ◽  
Insulin Dose ◽  
Glucose Production ◽  
Deficiency Anemia ◽  
Response Curves ◽  
Iron Deficient ◽  
Hepatic Glucose ◽  
Basal Plasma ◽  
Insulin Responsiveness

We performed euglycemic hyperinsulinemic glucose clamps at insulin infusion rates of 1.9, 4.0, 9.3, and 19.3 mU.kg-1 x min-1 in rats with varying severities of iron deficiency anemia (IDA; mean hemoglobin concentrations of 59, 79, 107, and 137 g/l) to assess the effect of IDA on insulin sensitivity and responsiveness. Glucose appearance and disappearance (Rd) rates were determined using a primed continuous infusion of [3-3H]glucose. Basal plasma glucose and insulin concentrations were similar between the IDA and control rats. Basal hepatic glucose production was significantly (P = 0.0001) elevated in the two most anemic groups (13.6 +/- 2.4 and 12.6 +/- 3.1 vs. 10.6 +/- 2.2 and 10.2 +/- 2.0 mg.kg-1 x min-1). A significant upward shift in the insulin dose-response curves for Rd indicated an increase in peripheral insulin responsiveness in the two most anemic groups while a slight leftward shift was suggestive of an increase in insulin sensitivity in all three anemic groups. Hepatic insulin sensitivity and responsiveness were unaffected by IDA. We conclude that increased glucose utilization rates in IDA rats are due primarily to an increase in peripheral insulin responsiveness.

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.

scholarly journals Differential impact of selective GH deficiency and endogenous GH excess on insulin-mediated actions in muscle and liver of male mice

2014 ◽  
Vol 307 (10) ◽  
pp. E928-E934 ◽  
Author(s):  
Jose Cordoba-Chacon ◽  
Manuel D. Gahete ◽  
Owen P. McGuinness ◽  
Rhonda D. Kineman
Keyword(s):  
Insulin Sensitivity ◽  
Gh Deficiency ◽  
Hepatic Glucose Production ◽  
Insulin Receptors ◽  
Glucose Production ◽  
Reciprocal Relationship ◽  
Hepatic Insulin Resistance ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Glucose ◽  
Gh Excess

A reciprocal relationship between insulin sensitivity and glucose tolerance has been reported in some mouse models and humans with isolated changes in growth hormone (GH) production and signaling. To determine if this could be explained in part by tissue-specific changes in insulin sensitivity, hyperinsulinemic-euglycemic clamps were performed in mice with adult-onset, isolated GH deficiency and in mice with elevated endogenous GH levels due to somatotrope-specific loss of IGF-I and insulin receptors. Our results demonstrate that circulating GH levels are negatively correlated with insulin-mediated glucose uptake in muscle but positively correlated with insulin-mediated suppression of hepatic glucose production. A positive relationship was also observed between GH levels and endpoints of hepatic lipid metabolism known to be regulated by insulin. These results suggest hepatic insulin resistance could represent an early metabolic defect in GH deficiency.

Interaction of free fatty acids and epinephrine in regulating hepatic glucose production in conscious dogs

2003 ◽  
Vol 284 (2) ◽  
pp. E291-E301 ◽  
Author(s):  
Chang An Chu ◽  
Pietro Galassetti ◽  
Kayano Igawa ◽  
Dana K. Sindelar ◽  
Doss W. Neal ◽  
...  
Keyword(s):  
Fatty Acids ◽  
High Glucose ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Conscious Dogs ◽  
Control Groups ◽  
Hepatic Glucose ◽  
Glycogenolytic Effect ◽  
Plasma Ffa ◽  
Arterial Plasma

To determine the effects of an increase in lipolysis on the glycogenolytic effect of epinephrine (EPI), the catecholamine was infused portally into 18-h-fasted conscious dogs maintained on a pancreatic clamp in the presence [portal (Po)-EPI+FFA, n = 6] and absence (Po-EPI+SAL, n = 6) of peripheral Intralipid infusion. Control groups with high glucose (70% increase) and free fatty acid (FFA; 200% increase; HG+FFA, n = 6) and high glucose alone (HG+SAL, n = 6) were also included. Hepatic sinusoidal EPI levels were elevated (Δ568 ± 77 and Δ527 ± 37 pg/ml, respectively) in Po-EPI+SAL and EPI+FFA but remained basal in HG+FFA and HG+SAL. Arterial plasma FFA increased from 613 ± 73 to 1,633 ± 101 and 746 ± 112 to 1,898 ± 237 μmol/l in Po-EPI+FFA and HG+FFA but did not change in EPI+SAL or HG+SAL. Net hepatic glycogenolysis increased from 1.5 ± 0.3 to 3.1 ± 0.4 mg · kg−1 · min−1( P < 0.05) by 30 min in response to portal EPI but did not rise (1.8 ± 0.2 to 2.1 ± 0.3 mg · kg−1 · min−1) in response to Po-EPI+FFA. Net hepatic glycogenolysis decreased from 1.7 ± 0.2 to 0.9 ± 0.2 and 1.6 ± 0.2 to 0.7 ± 0.2 mg · kg−1 · min−1by 30 min in HG+FFA and HG+SAL. Hepatic gluconeogenic flux to glucose 6-phosphate increased from 0.6 ± 0.1 to 1.2 ± 0.1 mg · kg−1 · min−1( P < 0.05; by 3 h) and 0.7 ± 0.1 to 1.6 ± 0.1 mg · kg−1 · min−1( P < 0.05; at 90 min) in HG+FFA and Po-EPI+FFA. The gluconeogenic parameters remained unchanged in the Po-EPI+SAL and HG+SAL groups. In conclusion, increased FFA markedly changed the mechanism by which EPI stimulated hepatic glucose production, suggesting that its overall lipolytic effect may be important in determining its effect on the liver.

scholarly journals The tumor suppressor TMEM127 regulates insulin sensitivity in a tissue-specific manner

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Subramanya Srikantan ◽  
Yilun Deng ◽  
Zi-Ming Cheng ◽  
Anqi Luo ◽  
Yuejuan Qin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Tumor Suppressor ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Suppressor Gene ◽  
Nutrient Sensing ◽  
Whole Body ◽  
Insulin Sensitizer

Abstract Understanding the molecular components of insulin signaling is relevant to effectively manage insulin resistance. We investigated the phenotype of the TMEM127 tumor suppressor gene deficiency in vivo. Whole-body Tmem127 knockout mice have decreased adiposity and maintain insulin sensitivity, low hepatic fat deposition and peripheral glucose clearance after a high-fat diet. Liver-specific and adipose-specific Tmem127 deletion partially overlap global Tmem127 loss: liver Tmem127 promotes hepatic gluconeogenesis and inhibits peripheral glucose uptake, while adipose Tmem127 downregulates adipogenesis and hepatic glucose production. mTORC2 is activated in TMEM127-deficient hepatocytes suggesting that it interacts with TMEM127 to control insulin sensitivity. Murine hepatic Tmem127 expression is increased in insulin-resistant states and is reversed by diet or the insulin sensitizer pioglitazone. Importantly, human liver TMEM127 expression correlates with steatohepatitis and insulin resistance. Our results suggest that besides tumor suppression activities, TMEM127 is a nutrient-sensing component of glucose/lipid homeostasis and may be a target in insulin resistance.

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