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F Assimacopoulos-Jeannet

Publications and source records attributed to F Assimacopoulos-Jeannet.

At least 55 records · Page 3Linked to original sources
PubMed1990

Hyperinsulinemia increases the amount of GLUT4 mRNA in white adipose tissue and decreases that of muscles: a clue for increased fat depot and insulin resistance.

To mimick a state of hyperinsulinemia, normal rats were infused with insulin for 4 days via minipumps, and compared to saline infused rats. At the end of the experimental period, the abundance of mRNA was increased in white adipose tissue (WAT) and decreased in muscles of "insulinized" rats compared to controls. These findings were accompanied, in all tissues considered, except the diaphragm, by parallel changes in the amount of the glucose transporter protein and by parallel changes in the in vivo glucose utilization index. Hyperinsulinemia is thus a driving force in stimulating adipose tissue metabolic activity, while bringing about incipient muscle insulin resistance.

Adipose Tissue↗
PubMed1989

The novel thermogenic beta-adrenergic agonist Ro 16-8714 increases the interscapular brown-fat beta-receptor-adenylate cyclase and the uncoupling-protein mRNA level in obese (fa/fa) Zucker rats.

In obese (fa/fa) rats both the total (-)-isoprenaline- and NaF-stimulated adenylate cyclase activities of interscapular brown-adipose-tissue (IBAT) plasma membranes were decreased as compared with lean rats by 40 and 38% respectively. An acute treatment with Ro 16-8714 increased (-)-isoprenaline- and NaF-stimulated adenylate cyclase activities by 2.5- and 2.0-fold respectively, and beta-adrenoceptor number 2.8-fold in obese rat IBAT, but it had no effect on these parameters in lean rats. It increased mRNA for mitochondrial uncoupling protein in both lean and obese rats to the same extent.

2-Hydroxyphenethylamine↗
PubMed1989

Dysregulation of glucose transport and transporters in perfused hearts of genetically obese (fa/fa) rats.

The regulation of glucose transport in normal and insulin-resistant obese rat hearts have been studied by measuring glucose transport via the efflux of labelled 3-0-methyl-D-glucose. Glucose transporters in obese rat hearts were also investigated using the labelled cytochalasin B-binding assay. Basal, and insulin- or increasing workload-induced stimulation of glucose transport was decreased in obese rat hearts compared to those of normal ones. Total number of glucose transporters (plasma membrane plus microsomal ones) was about half that previously reported for normal rat hearts. Insulin or workload favoured the translocation of glucose transporters from an intercellular pool (microsomes) to the plasma membrane, as they do in normal rats. Due to the measured decrease in total number of transporters of obese rat hearts, those present in the plasma membrane (under basal conditions, or following stimulation by insulin or workload) were less than those previously found in normal rat hearts tested under identical conditions. In obese rat hearts, regulation of plasma membrane transporters was perturbed. The Hill coefficient (an index of positive cooperativity amongst glucose transporters) was paradoxically decreased by insulin while leaving affinity values unaltered. The Hill coefficient was unaltered by workload, although the affinity values were increased compared to respective controls. To sum up, obese rat hearts have decreased total transporter number, and although the two stimuli studied favour the translocation of available transporters, they fail to "activate" them adequately once present in the plasma membrane.

3-O-Methylglucose↗
PubMed1988

Effects of insulin on glucose transport and glucose transporters in rat heart.

The effect of insulin on glucose transport and glucose transporters was studied in perfused rat heart. Glucose transport was measured by the efflux of labelled 3-O-methylglucose from hearts preloaded with this hexose. Insulin stimulated 3-O-methylglucose transport by: (a) doubling the maximal velocity (Vmax); (b) decreasing the Kd from 6.9 to 2.7 mM; (c) increasing the Hill coefficient toward 3-O-methylglucose from 1.9 to 3.1; (d) increasing the efficiency of the transport process (k constant). Glucose transporters in enriched plasma and microsomal membranes from heart were quantified by the [3H]cytochalasin-B-binding assay. When added to normal hearts, insulin produced the following changes in the glucose transporters: (a) it increased the translocation of transporters from an intracellular pool to the plasma membranes; (b) it increased (from 1.6 to 2.7) the Hill coefficient of the transporters translocated into the plasma membranes toward cytochalasin B, suggesting the existence of a positive co-operativity among the transporters appearing in these membranes; (c) it increased the affinity of the transporters (and hence, possibly, of glucose) for cytochalasin B. The data provide evidence that the stimulatory effect of insulin on glucose transport may be due not to the sole translocation of intracellular glucose transporters to the plasma membrane, but to changes in the functional properties thereof.

3-O-Methylglucose↗
PubMed1987

Insulin modifies the properties of glucose transporters in rat brown adipose tissue.

The properties of glucose transporters associated with plasma and microsomal membranes have been studied in brown adipose tissue of rats after treatment by saline infusion or hyperinsulinaemic/euglycaemic clamp. In this tissue, insulin produces a 40-fold increase in glucose utilization as measured by the 2-deoxy-D-glucose technique, and therefore a 40-fold increase in the rate-limiting glucose transport. This increase, promoted by insulin, is associated with: (a) translocation of the transporters from a pool associated with the microsomal fraction to the plasma membrane without modification of the total number of transporters; (b) an increase in the Hill coefficient of the plasma-membrane glucose transporters for cytochalasin B from 1.1 to 2.5, indicating the presence of positive co-operativity; (c) a decrease in the Kd (apparent dissociation constant) of the transporters towards cytochalasin B from 148 to 82 nM; (d) no change in the Hill coefficient or Kd for the transporters associated with the microsomal membranes. These data indicate that, in addition to causing translocation of the glucose transporters, insulin modifies their properties and behaviour towards cytochalasin B. This may reflect modifications in their properties and behaviour towards glucose, and by this contribute to bringing about the marked effect of this hormone on glucose transport in brown adipose tissue.

Adipose Tissue, Brown↗
PubMed1987

Stimulatory effect of cold adaptation on glucose utilization by brown adipose tissue. Relationship with changes in the glucose transporter system.

The effect of cold adaptation (4 degrees C) on the in vivo glucose utilization and on the number and properties of the glucose transporters has been studied in brown adipose tissue of normal rats. Glucose utilization was assessed in vivo by the 2-deoxyglucose method. Glucose transporters in plasma and microsomal membranes were quantified by the [3H]cytochalasin B-binding assay. After cold adaptation the in vivo glucose utilization by brown adipose tissue increased 21-fold compared to controls (22 degrees C). The number of glucose transporters in plasma membranes of brown adipose tissue increased from 75 to 436 pmol/g tissue and that of total glucose transporters (plasma + microsomal membranes) from 438 to 754 pmol/g tissue. In addition, cold adaptation increased the Hill coefficient of the plasma membrane transporter for cytochalasin B from 0.90 to 2.03 and decreased the Kd from 100 to 54 nM. This study shows that cold adaptation promotes: a translocation of glucose transporters from an intracellular pool to plasma membranes; an increased number of plasma membrane glucose transporters unaccounted for by the translocation process (e.g. "de novo" synthesis); an increase in the Hill coefficient for cytochalasin B that could also represent changes in the properties of the transporters vis-à-vis glucose, (e.g. positive cooperativity); and a decrease in the Kd value for cytochalasin B.

Acclimatization↗
PubMed1987

Differential effect of steady-state hyperinsulinaemia and hyperglycaemia on hepatic glycogenolysis and glycolysis in rats.

The action of glucose and of insulin on hepatic glucose production and metabolism has been studied in fed anaesthetized rats during hyperinsulinaemic clamp combined with various steady state levels of glycaemia (6.8 +/- 0.1, 9.3 +/- 0.1, 11.8 +/- 0.1 mmol/l). Hepatic glucose production was measured using constant infusion of D-[6-3H] glucose. At the end of each clamp the liver was freeze clamped, and enzyme activities and metabolites were measured. Hepatic glucose production was totally suppressed in all the groups receiving insulin. In the group with steady-state normoglycaemia, the suppression of hepatic glucose production was accompanied by a decrease in the levels of glucose-6-phosphate, an increase in those of fructose 2,6-bisphosphate and glycolytic intermediates, but without change in glycogen level or glycogen synthase and phosphorylase. In contrast, in the groups with steady-state hyperglycaemia, phosphorylase a was inactivated, and glycogen synthase activated. Under these conditions, glucose-6-phosphate levels were also decreased and those of fructose 2,6-bisphosphate and glycolytic intermediates were higher than in the group with steady-state normoglycaemia. A slight drop in the level of cAMP was also observed which may contribute, with hyperglycaemia, to the inactivation of phosphorylase. Incorporation of tritiated water into liver glycogen paralleled the activation of glycogen synthase and the accumulation of glycogen. The data indicate that, at normoglycaemia, insulin may suppress hepatic glucose production by channeling glucose-6-phosphate into the glycolytic pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Vasopressin and/or glucagon rapidly increases mitochondrial calcium and oxidative enzyme activities in the perfused rat liver.

Mitochondria were prepared by a method including a Percoll purification step after the rapid homogenization of livers of fed rats which had been perfused either under unstimulated conditions or in the presence of vasopressin and/or glucagon. The two hormones separately or together increased the total calcium content of the mitochondria. This enhancement was accompanied by parallel increases in activities of the Ca2+-sensitive intramitochondrial enzymes pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase. The effects of the two hormones on total mitochondrial calcium and on the activities of the oxidative enzymes were additive. The persistent enhancements of mitochondrial calcium content and enzyme activities were partially reversed by the addition of Na+ ions to the mitochondrial incubations; these effects of Na+ were blocked by diltiazem, a selective inhibitor of Na+-induced Ca2+ release. Mitochondria from control livers were incubated in vitro with CaCl2 to achieve various calcium content, and mitochondrial enzyme activities and calcium content were measured. A good correlation was obtained between the total calcium content and the activities of pyruvate dehydrogenase and oxoglutarate dehydrogenase. The results obtained are consistent with the hypothesis that vasopressin and glucagon additively cause increases in intramitochondrial [Ca2+] and so bring about the activations of these key enzymes of mitochondrial oxidative metabolism.

Adenosine Triphosphate↗
PubMed1986

Inhibition of hepatic glucose production by insulin in vivo in rats: contribution of glycolysis.

The action of insulin on hepatic glucose production (HGP) has been studied in fed anesthetized rats during a euglycemic hyperinsulinemic clamp. At the end of the clamp, the liver was rapidly removed, frozen, and enzyme activities and metabolites were measured. When insulin totally suppressed HGP, it did not modify glycogen phosphorylase or synthase activity, nor did it "spare" or increase glycogen content. Insulin decreased glucose 6-phosphate while increasing glycolytic intermediates (fructose 1,6-bisphosphate, alpha-glycerophosphate, lactate, and pyruvate) as well as fructose 2,6-bisphosphate, the potent effector of 6-phosphofructo-1-kinase. Insulin also increased pyruvate kinase activity of low substrate concentration. Lipogenesis measured with 3H2O incorporation into fatty acids was increased four-to fivefold by insulin. The data suggest that in normal rat liver, when glycemia is maintained at constant basal level, insulin promotes no change in glycogen metabolism, whereas the hormone stimulates the glycolytic pathway. This action contributes to the suppression of hepatic glucose production observed after the addition of the hormone.

Animals↗
PubMed1986

Severe hepatic and peripheral insulin resistance as evidenced by euglycemic clamps in genetically obese fa/fa rats.

The action of insulin on glucose metabolism and hepatic glucose production was studied in vivo over a wide range of insulin concentrations in lean and genetically obese (fa/fa) rats, using the euglycemic clamp technique. While total glucose metabolism was stimulated 3-fold by insulin in lean animals (half-maximal stimulation at 400 microU/ml insulin), the hormone had no significant effect on glucose metabolism in obese animals, whatever the concentration used. In lean rats, the endogenous (i.e. hepatic) glucose production was completely suppressed at a steady state insulin concentration of about 360 microU/ml. In obese rats, an insulin concentration as high as 10,000 microU/ml was needed to suppress the hepatic glucose production. These results suggest that, in obese rats 1) basal plasma insulin levels appear to maximally stimulate peripheral glucose metabolism, and the presence of postreceptor defects prevents any further stimulatory effect of the hormone on glucose metabolism; 2) grave impairments of the action of insulin on hepatic glucose production are present, despite a normal responsiveness obtained at pharmacological concentrations of the hormone. These hepatic alterations could be due to postbinding and/or intracellular defects, as well as to defects, yet to be defined, of the homeostasis of insulin counterregulatory hormones.

Animals↗
PubMed1984

Modulation of beta-oxidation and proton conductance pathway of brown adipose tissue in hypo- and hyperinsulinemic states.

The metabolic capacity of interscapular brown adipose tissue of hypoinsulinemic (diabetic) rats is decreased and a reduced beta-oxidative capacity contributes to this metabolic alteration. It was thus of interest to compare, in diabetic and in chronically (8 days) insulin-infused rats, the beta-oxidative capacity and indices of the thermogenic state (GDP-binding and 32 000 Mr protein) in this tissue. Mitochondrial GDP-binding and 32 000 Mr protein were both decreased in diabetic rats compared to appropriate controls and markedly increased as was also the beta-oxidative capacity in hyperinsulinemic rats.

Adipose Tissue↗
PubMed1984

Increased insulin responsiveness in vivo and in vitro consequent to induced hyperinsulinemia in the rat.

The effect of constant, controlled hyperinsulinemia on in vivo and in vitro insulin responsiveness has been investigated in rats that have received insulin infusions through chronically implanted jugular vein catheters. Constant rates of insulin infusion during days 1-4 resulted in stable plasma insulin concentrations. The plasma glucose initially fell from 122 +/- 3 to 53 +/- 4 mg/dl. While the infusion rate was maintained constant, the plasma glucose continued to fall over the subsequent days so that on day 4 the plasma glucose, 40 +/- 2 mg/dl, was significantly lower than that in the same animals on day 1 (P less than 0.02). Subsequently, the rate of insulin infusion was decreased to maintain the plasma glucose level in the 35-40 mg/dl range. Plasma catecholamine levels were high in insulin-infused rats. On the eighth day an in vivo insulin tolerance test (0.5 U/kg) was performed. Insulin-infused rats responded with a hypoglycemia that was both more pronounced and longer sustained than in saline-infused controls. Insulin responsiveness in vitro has been measured in isolated adipocytes. Adipocytes from epididymal fat pads were of similar size in the two groups of animals. Glucose uptake by adipocytes from insulin-infused rats was similar to that of controls under basal (zero insulin) conditions, but showed an increase in the maximum response to insulin. Glucose incorporation into total lipid and fatty acid was greater in adipocytes from insulin-infused rats than in controls under both basal (zero insulin) and insulin-stimulated conditions. Activities of the lipogenic enzymes acetyl CoA carboxylase and fatty acid synthetase were markedly increased in epididymal fat pads of insulin-infused rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyl-CoA Carboxylase↗
PubMed1983

Altered liver glycogen metabolism in fed genetically obese mice.

The cyclic AMP and glycogen concentrations and the activities of phosphorylase kinase, phosphorylase a and glycogen synthase a were not different in livers from lean or ob/ob mice despite increased plasma glucose and insulin in the obese group. The liver water content was decreased by 10% in the obese mice. In hepatocytes isolated from lean mice and incubated with increasing glucose concentrations (14-112 mM), a sequential inactivation of phosphorylase and activation of glycogen synthase was observed. In hepatocytes from obese mice the inactivation of phosphorylase was not followed by an activation of synthase. The inactivation of phosphorylase occurred more rapidly and was followed by an activation of synthase in hepatocytes isolated from both groups of mice when in the incubation medium Na+ was replaced by K+ or when Ca2+ was omitted and 2.5 mM-EGTA included. The inactivation of phosphorylase and activation of synthase were not different in broken-liver-cell preparations from lean and obese animals. The re-activation of phosphorylase in liver filtrates in the presence of 0.1 microM-cyclic AMP and MgATP was inhibited by about 70% by EGTA and stimulated by Ca2+ and was always greater in preparations from ob/ob mice. The apparent paradox between the impairment of glycogen metabolism in isolated liver preparations and the situation in vivo in obese mice is discussed.

Animals↗
PubMed1983

Lack of vasopressin receptors in liver, but not in kidney, of ob/ob mice.

The activity of phosphorylase a was measured in isolated hepatocytes from fed lean and ob/ob mice after addition of vasopressin, angiotensin, phenylephrine and glucagon. The binding of these hormones to purified liver plasma membranes was also determined. In hepatocytes of ob/ob mice, no increase in phosphorylase a was measured after addition of vasopressin, whereas the other hormones promoted an increase in the activity of the enzyme. No specific vasopressin receptors could be measured on purified liver plasma membrane of ob/ob mice. A decrease in the number of receptors for angiotensin and glucagon, without modification of the affinity, was also observed. No restoration of the number of vasopressin receptors was observed in liver of ob/ob mice starved for 3 days or in younger (5-6 weeks) animals. Vasopressin receptors and vasopressin-stimulated adenylate cyclase, measured on purified kidney medulla membranes, were similar in both lean and ob/ob mice. The data indicate a selective lack of vasopressin receptors and metabolic response in liver of the ob/ob mouse.

Animals↗
PubMed1983

Effect of phenylephrine on pyruvate dehydrogenase activity in rat hepatocytes and its interaction with insulin and glucagon.

In isolated rat hepatocytes phenylephrine promotes a rapid increase in the amount of pyruvate dehydrogenase present in its active form (PDHa). This action is mediated by alpha 1-adrenergic receptors and is not observed in Ca2+-depleted hepatocytes. It is mimicked by the Ca2+ ionophore A23187. No changes in metabolites known to affect PDH activity are measured 3 min after addition of phenylephrine. Glucagon also increases PDHa, its action is additive to that of phenylephrine. The action of phenylephrine on PDHa could be explained by an increase in mitochondrial free Ca2+.

Animals↗
PubMed1983

Fatty acid utilization and purine nucleotide binding in brown adipose tissue of genetically obese (ob/ob) mice.

The activities of the main enzymes involved in fatty acid utilization i.e. palmitoyl CoA synthetase as well as peroxisomal and mitochondrial beta-oxidation were measured in brown adipose tissue homogenates of lean and ob/ob mice kept at 23 degrees C or acclimated at 4 degrees C. The proton conductance pathway, i.e. the number of purine nucleotide (GDP) binding sites and the percentage of 32,000 polypeptide in brown adipose tissue mitochondria were also measured. In the ob/ob mice at 23 degrees C, the specific activities of the palmitoyl CoA synthetase and of the beta-oxidation as well as the number of GDB binding sites were lower than in the lean mice by 26%, 43% and 37%, respectively. The percentage of 32,000 polypeptide, however, was the same in both groups. In the ob/ob mice at 23 degrees C, the lower homogenate beta-oxidation specific activity was due to the fact that the peroxisomal and mitochondrial specific activities were 44% and 37% lower, respectively. Cold acclimation at 4 degrees C was found to cause an increase of the palmitoyl CoA synthetase specific activity, of the palmitoyl CoA synthetase and peroxisomal beta-oxidation total activities and of the number of GDP binding sites, in both lean and ob/ob mice. Cold acclimation increased the percentage of 32,000 polypeptide in the ob/ob mice only.

Adipose Tissue, Brown↗