Insulin sensitivity of rates of glycolysis and glycogen synthesis in soleus, stripped soleus, epitrochlearis, and hemi-diaphragm muscles isolated from sedentary rats

1983 ◽  
Vol 3 (7) ◽  
pp. 675-679 ◽  
Author(s):  
R. A. J. Challiss ◽  
J. Espinal ◽  
E. A. Newsholme
Keyword(s):  
Fatty Acid ◽  
Glucose Utilization ◽  
Glycogen Synthesis ◽  
Maximal Inhibition ◽  
Maximal Stimulation ◽  
Glucose Fatty Acid Cycle ◽  
Isolated Adipocytes ◽  
Stimulation Of

The effect of insulin concentrations on the rates of glycolysis and glycogen synthesis in four different in vitro rat muscle preparations (intact soleus, stripped soleus, epitrochlearis, and hemi-diaphragm) were investigated: the concentrations of insulin that produced half-maximal stimulation of the rates of these two processes in the four muscle preparations were similar – about 100 μunits/ml. This is at least 10-fold greater than the concentration that produced half-maximal inhibition of lipolysis in isolated adipocytes. Since 100 μunits/ml insulin is outside the normal physiological range in the rat, it is suggested that, in vivo, insulin influences glucose utilization in muscle mainly indirectly, via changes in the plasma fatty acid levels and the ‘glucose/fatty acid cycle’. Consequently the view that insulin stimulates glucose utilization in muscle mainly by a direct effect on membrane transport must be treated with caution.

Abstract 344: FNDC5, a PGC1-a-Dependent Myokine, Increases Glucose Utilization and Fatty-Acid Oxidation by AMPK Signaling Pathway

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Ling Tao ◽  
Yi Liu ◽  
Chao Xin ◽  
Weidong Huang ◽  
Lijian Zhang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Glucose Uptake ◽  
Fatty Acid Oxidation ◽  
Glucose Utilization ◽  
C2c12 Cells ◽  
Time Dependent ◽  
Acid Oxidation ◽  
Ampk Signaling

FNDC5 is a hormone secreted by myocytes that could reduce obesity and insulin resistance, However, the exact effect of FNDC5 on glucose and lipid metabolism remain poorly identified; More importantly, the signaling pathways that mediate the metabolic effects of FNDC5 is completely unknown. Here we showed that FNDC5 stimulates β-oxidation and glucose uptake in C2C12 cells in a dose- and time-dependent fashion in vitro (n=8, all P<0.01). In vivo study revealed that FNDC5 also enhanced glucose tolerance in diabetic mice and increased the glucose uptake evidenced by increased [18F] FDG accumulation in hearts by PET scan (n=6, all P<0.05). FNDC5 decreased the expression of gluconeogenesis related molecules (PEPCK and G6Pase) and increased the phosphorylation of ACC, a key modulator of fatty-acid oxidation, both in hepatocytes and C2C12 cells (n=3, all P<0.05). In parallel with its stimulation of β-oxidation and glucose uptake, FNDC5 increased the phosphorylation of AMPK both in hepatocytes and C2C12 cells in a dose- and time-dependent fashion in vitro and in vivo. More importantly, the β-oxidation and glucose uptake, the expression of PEPCK and G6Pase and the phosphorylation of ACC induced by FNDC5 were attenuated by AMPK inhibitor in hepatocytes and C2C12 cells (P<0.05). Most importantly, the FNDC5 induced glucose uptake and phosphorylation of ACC were attenuated in AMPK-DN mice (n=6, all P<0.05). The glucose-lowering effect of FNDC5 in diabetic mice was also attenuated by AMPK inhibitor. Our data presents the direct evidence that FNDC5 stimulates glucose utilization and fatty-acid oxidation by AMPK signaling pathway, suggesting that FNDC5 be a novel pharmacological approach for type 2 diabetes.

scholarly journals The effects of amylin on carbohydrate metabolism in skeletal muscle in vitro and in vivo

1990 ◽  
Vol 269 (1) ◽  
pp. 19-23 ◽  
Author(s):  
B Leighton ◽  
E Foot
Keyword(s):  
Glucose Utilization ◽  
Glycogen Synthesis ◽  
Intraperitoneal Administration ◽  
Muscle Preparation ◽  
Glucose Incorporation ◽  
Rat Soleus Muscle ◽  
Lactate Formation ◽  
Human Amylin

1. The effects of synthetic human amylin on basal and insulin-stimulated (100 and 1000 microunits/ml) rates of lactate formation, glucose oxidation and glycogen synthesis were measured in the isolated rat soleus muscle preparation incubated in the presence of various concentrations of glucose (5, 11 and 22 mM). 2. The rate of glucose utilization was increased by about 2-fold by increasing the glucose concentration from 5 to 22 mM. 3. Synthetic human amylin (10 nM) significantly inhibited (by 46-56%) glycogen synthesis, irrespective of the concentration of insulin or glucose present in the incubation medium. 4. Amylin (10 nM) did not affect insulin-stimulated rates of 2-deoxy[3H]glucose transport and phosphorylation. 5. Intraperitoneal administration of insulin (100 micrograms/kg) to rats in vivo stimulated the rate of [U-14C]glucose incorporation into glycogen in the diaphragm by about 80-fold. This rate was decreased (by 28%) by co-administration of amylin (66 micrograms/kg).

scholarly journals Stimulation of creatine kinase activity in rat skeletal tissue in vivo and in vitro by protease-resistant variants of parathyroid hormone fragments

1995 ◽  
Vol 309 (1) ◽  
pp. 85-90 ◽  
Author(s):  
D Sömjen ◽  
V Vargas ◽  
A Waisman ◽  
E Wingender ◽  
W Tegge ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Parathyroid Hormone ◽  
Double Mutant ◽  
Bone Cells ◽  
Specific Activity ◽  
Control Level ◽  
Maximal Stimulation ◽  
Stimulation Of

We have reported that mid-region fragments of human parathyroid hormone (hPTH), exemplified by hPTH-(28-48), stimulated [3H]thymidine incorporation into DNA and increased the specific activity of the brain-type isoenzyme of creatine kinase (CK) in both skeletal-derived cell cultures (ROS 17/2.8 cells) and immature rat epiphyseal cartilage and diaphyseal bone, without stimulating cyclic AMP synthesis which is a prerequisite for bone resorption. In the present study, substitution of amino acids in hPTH-(28-48), which resulted in increased resistance to proteolysis, produced variants that stimulated skeletal systems at two orders of magnitude lower concentration than the wild-type fragment. We modified hPTH-(28-48) at Leu-37 by replacement with Met, Thr or Val. Under conditions in which 20% of the native hPTH-(28-48) resisted proteolysis by cathepsin D for 6 h, approx. 40% of the L37V mutant and 70% of the L37T mutant remained intact. Substitution of Met for Phe-34 in addition to Thr for Leu-37, or the substitution of Met for Phe-34 alone, produced 100%-resistant fragments. These variants at residue 34 caused maximal stimulation of CK in ROS 17/2.8 cells at 0.24 nM compared with 24 nM for hPTH-(28-48). The double mutant stimulated CK activity significantly in immature rats, at a minimum dose of 12.5 ng/rat, and caused maximal stimulation at 125 ng/rat, a 10-fold lower dose than for hPTH-(28-48). The effect of the double mutant lasted up to 24 h which differs from the stimulation by hPTH-(28-48) in which CK specific activity returns to the control level at 24 h. This same dose also significantly stimulated CK activity in gonadectomized rats. These results show the advantage of using protease-resistant mid-region variants of hPTH-(28-48) to stimulate bone cells, in terms of lower doses and longer duration of effectiveness, both in vitro and in vivo.

scholarly journals Regulation of lipogenesis. Stimulation of fatty acid synthesis in vivo and in vitro in the liver of the newly hatched chick

1970 ◽  
Vol 118 (2) ◽  
pp. 259-263 ◽  
Author(s):  
Alan G. Goodridge
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Latent Form ◽  
Triose Phosphate ◽  
Liver Slices ◽  
Stimulation Of

1. A single glucose meal stimulated the incorporation of acetate into fatty acids in liver slices. If the glucose was added in vitro, it had no effect. Fructose and glycerol in vitro markedly stimulated fatty acid synthesis from acetate. Fructose and glycerol probably by-passed a rate-controlling reaction between glucose and triose phosphate. This reaction may have been stimulated by glucose administered in vivo. 2. The stimulation of fatty acid synthesis caused by fructose did not require the synthesis of enzyme, thus indicating that fatty acid-synthesizing enzymes were present in a latent form in the livers from unfed chicks.

Acute metabolic effects of adrenergic agents in swine

1987 ◽  
Vol 252 (1) ◽  
pp. E85-E95 ◽  
Author(s):  
H. J. Mersmann
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Plasma Free Fatty Acid ◽  
Metabolic Effects ◽  
Adipose Tissue Lipolysis ◽  
Beta 2 ◽  
Stimulation Of

A pig model in vivo was used to confirm the unique specificity for stimulation of porcine adipose tissue lipolysis by norepinephrine analogues in vitro. Plasma free fatty acid and blood glycerol concentrations were monitored as probable indicators of adipose tissue lipolysis. Plasma glucose and lactate concentrations, blood pressure, and heart rate were monitored also. Norepinephrine analogues were infused intravenously. Several compounds, classified as either beta 1- or beta 2-adrenergic agonists, that stimulated lipolysis in vitro also increased plasma free fatty acid and blood glycerol concentrations in vivo. Tazolol (beta 1) and quinterenol (beta 2) did not stimulate lipolysis in vitro and likewise did not elevate plasma free fatty acid or blood glycerol concentrations in vivo. Clenbuterol and zinterol did not stimulate lipolysis in vitro but elevated plasma free fatty acid concentrations in vivo, implying indirect effects. Isoproterenol stimulation of plasma free fatty acid and blood glycerol concentrations in vivo was antagonized by propranolol, implying the beta-adrenergic nature of the receptors. Infusion of purported beta 1- and beta 2-adrenergic antagonists suggested control of lipolysis in vivo predominantly by beta 1-adrenergic receptors; however, because the results in vitro do not indicate this specificity, differential pharmacodynamics of the antagonists are suggested rather than designation of receptor subtypes. There was no evidence for alpha-adrenergic mediated inhibition of adipose tissue lipolysis in vivo, confirming observations in vitro.

scholarly journals Stimulation of astrocyte fatty acid oxidation by thyroid hormone is protective against ischemic stroke-induced damage

2016 ◽  
Vol 37 (2) ◽  
pp. 514-527 ◽  
Author(s):  
Naomi L Sayre ◽  
Mikaela Sifuentes ◽  
Deborah Holstein ◽  
Sheue-yann Cheng ◽  
Xuguang Zhu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Fatty Acid ◽  
Stroke Volume ◽  
Fatty Acid Oxidation ◽  
Glucose Deprivation ◽  
Acid Oxidation ◽  
Atp Production ◽  
Stimulation Of

We previously demonstrated that stimulation of astrocyte mitochondrial ATP production via P2Y1 receptor agonists was neuroprotective after cerebral ischemic stroke. Another mechanism that increases ATP production is fatty acid oxidation (FAO). We show that in primary human astrocytes, FAO and ATP production are stimulated by 3,3,5 triiodo-l-thyronine (T3). We tested whether T3-stimulated FAO enhances neuroprotection, and show that T3 increased astrocyte survival after either hydrogen peroxide exposure or oxygen glucose deprivation. T3-mediated ATP production and protection were both eliminated with etomoxir, an inhibitor of FAO. T3-mediated protection in vitro was also dependent on astrocytes expressing HADHA (hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase), which we previously showed was critical for T3-mediated FAO in fibroblasts. Consistent with previous reports, T3-treatment decreased stroke volumes in mice. While T3 decreased stroke volume in etomoxir-treated mice, T3 had no protective effect on stroke volume in HADHA +/− mice or in mice unable to upregulate astrocyte-specific energy production. In vivo, 95% of HADHA co-localize with glial-fibrillary acidic protein, suggesting the effect of HADHA is astrocyte mediated. These results suggest that astrocyte-FAO modulates lesion size and is required for T3-mediated neuroprotection post-stroke. To our knowledge, this is the first report of a neuroprotective role for FAO in the brain.

scholarly journals Effect of ppGpp on Escherichia coliCyclopropane Fatty Acid Synthesis Is Mediated through the RpoS Sigma Factor (ςS)

1999 ◽  
Vol 181 (2) ◽  
pp. 572-576 ◽  
Author(s):  
Johannes Eichel ◽  
Ying-Ying Chang ◽  
Dieter Riesenberg ◽  
John E. Cronan
Keyword(s):  
Fatty Acid ◽  
Sigma Factor ◽  
Direct Interaction ◽  
Acid Synthesis ◽  
Cyclopropane Fatty Acid ◽  
In Vivo Experiments ◽  
Direct Regulator ◽  
Stimulation Of

ABSTRACT Strains of Escherichia coli carrying mutations at therelA locus are deficient in cyclopropane fatty acid (CFA) synthesis, a phospholipid modification that occurs as cultures enter stationary phase. RelA protein catalyzes the synthesis of guanosine-3′,5′-bisdiphosphate (ppGpp); therefore, ppGpp was a putative direct regulator of CFA synthesis. The nucleotide could act by increasing either the activity or the amount of CFA synthase, the enzyme catalyzing the lipid modification. We report that the effect of RelA on CFA synthesis is indirect. In vitro and in vivo experiments show no direct interaction between ppGpp and CFA synthase activity. TherelA effect is due to ppGpp-engendered stimulation of the synthesis of the alternative sigma factor, RpoS, which is required for function of one of the two promoters responsible for expression of CFA synthase.

Early alteration of insulin stimulation of PI 3-kinase in muscle and adipocyte from gold thioglucose obese mice

1995 ◽  
Vol 268 (4) ◽  
pp. E604-E612 ◽  
Author(s):  
S. J. Heydrick ◽  
N. Gautier ◽  
C. Olichon-Berthe ◽  
E. Van Obberghen ◽  
Y. Le Marchand-Brustel
Keyword(s):  
Insulin Receptor ◽  
Tyrosine Phosphorylation ◽  
Glycogen Synthesis ◽  
Lipid Synthesis ◽  
Obese Mice ◽  
Insulin Stimulation ◽  
Gold Thioglucose ◽  
Stimulation Of

The activation of phosphatidylinositol 3-kinase (PIK) was studied in vivo and in vitro in soleus muscle and adipocytes from young (8 wk) and old (30 wk) gold thioglucose obese mice. Insulin resistance assessed from muscle glucose transport and glycogen synthesis was present both in young and old obese mice. Adipocyte lipid synthesis and muscle glycolysis or glucose oxidation are not defective in young obese mice but become resistant later on. After incubation with 50 nM insulin, muscle antiphosphotyrosine-immunoprecipitable PIK activity was stimulated 5- to 10-fold in both young and old animals. This response was impaired by 56 and 75% in muscles from young and old obese mice, respectively. Insulin stimulation of receptor tyrosine kinase activity was only slightly decreased in muscle of young obese mice, whereas insulin receptor substrate 1 (IRS-1) tyrosine phosphorylation was blunted. The altered PIK stimulation in muscle, which is present both in vivo and in vitro, is thus characterized by a reduced association of PIK activity with IRS-1 and appears to result from a diminished IRS-1 tyrosine phosphorylation. In adipocytes isolated from lean mice, antiphosphotyrosine-immunoprecipitable PIK increased 25-fold within 10 min of incubation with insulin. This stimulation was markedly altered both in young and old obese mice, whereas lipogenesis was insulin resistant only in old obese animals. In adipocytes from young obese mice, insulin's stimulatory effect on the phosphorylation of insulin receptor beta-subunit, pp60, and an exogenous substrate was normal, whereas IRS-1 tyrosine phosphorylation was markedly depressed.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Eicosapentaenoic fatty acid increases leptin secretion from primary cultured rat adipocytes: role of glucose metabolism

2005 ◽  
Vol 288 (6) ◽  
pp. R1682-R1688 ◽  
Author(s):  
Patricia Pérez-Matute ◽  
Amelia Marti ◽  
J. Alfredo Martínez ◽  
M. P. Fernández-Otero ◽  
Kimber L. Stanhope ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Glucose Metabolism ◽  
Glucose Utilization ◽  
Lactate Production ◽  
Metabolic Effects ◽  
Rat Adipocytes ◽  
Glucose And Lipid Metabolism ◽  
Eicosapentaenoic Fatty Acid

Eicosapentaenoic acid (EPA), one of the n-3 polyunsaturated fatty acids, has been shown to stimulate leptin mRNA expression and secretion in 3T3-L1 cells. However, other studies have reported inhibitory effects of EPA on leptin expression and secretion in vivo and in vitro. To determine the direct effects of EPA on basal and insulin-stimulated leptin secretion, isolated rat adipocytes were incubated with EPA in the absence and presence of insulin. EPA (10, 100, and 200 μM) increased basal leptin gene expression and secretion (+43.8%, P < 0.05; +71.1%, P < 0.01; and +73.7%, P < 0.01, respectively). EPA also increased leptin secretion in the presence of 1.6 nM insulin; however, the effect was less pronounced than in the absence of it. Because adipocyte glucose and lipid metabolism are involved in the regulation of leptin production, the metabolic effects of this fatty acid were also examined. EPA (200 μM) increased basal glucose uptake in isolated adipocytes (+50%, P < 0.05). Anaerobic metabolism of glucose, as assessed by lactate production and proportion of glucose metabolized to lactate, has been shown to be inversely correlated to leptin secretion and was decreased by EPA in both the absence and presence of insulin. EPA increased basal glucose oxidation as determined by the proportion of 14C-labeled glucose metabolized to CO2. Lipogenesis (14C-labeled glucose incorporation into triglyceride) was decreased by EPA in the absence of insulin, whereas lipolysis (glycerol release) was unaffected. The EPA-induced increase of basal leptin secretion was highly correlated with increased glucose utilization ( r = +0.89, P < 0.01) and inversely related to the anaerobic glucose metabolism to lactate. EPA’s effect on insulin-stimulated leptin secretion was not related to increased glucose utilization but was inversely correlated with anaerobic glucose metabolism to lactate ( r = −0.84, P < 0.01). Together, the results suggest that EPA, like insulin, stimulates leptin production by increasing the nonanaerobic/oxidative metabolism of glucose.

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