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Biomedical subjects

L Girardier

Publications and source records attributed to L Girardier.

At least 55 records · Page 3Linked to original sources
PubMed1986

The response of adipose tissue blood flow to insulin-induced hypoglycemia in conscious dogs and rats.

A comparative study, focusing on the modification of regional blood flow in adipose tissue during insulin-induced hypoglycemia, was performed on dogs and rats at room temperature (22 degrees C) and on rats at thermoneutrality (28-32 degrees C). Insulin dosages of 3 IU/kg in rats and 0.75 IU/kg in dogs were found to cause changes of comparable amplitude and kinetics in plasma glucose and catecholamine levels in both species. At thermoneutrality, hypoglycemia induced an increase in blood supply to adipose tissue in both species: in dogs, blood flow density was markedly increased from the periphery (+75% in subcutaneous region) to the deeper locations (+550% in perirenal region); in rats, the increase of fractional cardiac output was especially pronounced in brown adipose tissue. By contrast, in rats acclimated at room temperature, hypoglycemia induced a decrease of fractional cardiac output to white adipose tissue and even more markedly, to brown adipose tissue (-45%). These results strongly suggest that, in rats at ambient temperature below thermoneutrality, thermoregulatory heat production is shut off during hypoglycemia.

Acclimatization↗
PubMed1986

Effect of nafenopin, a peroxisome proliferator, on energy metabolism in the rat as a function of acclimation temperature.

The effects of the peroxisome proliferator, nafenopin, on body temperature, apparent gross food efficiency and activity of interscapular brown adipose tissue (IBAT) peroxisomes and mitochondria of rats acclimated at 23 degrees C or at 32 degrees C have been studied. In 23 degrees C-acclimated rats, nafenopin treatment induced an atrophy of IBAT characterized by a decrease of tissue wet weight, of amounts of mitochondrial and peroxisomal proteins and of mitochondrial total succinate dehydrogenase activity to 67%, 67%, 65% and 57%, respectively of control values. It also resulted in a 1.9-fold stimulation of peroxisome total acyl CoA oxidase activity and had no effect on apparent gross food efficiency or colonic temperature. Acclimation at 32 degrees C per se induced an atrophy of IBAT and a decrease of total catalase and acyl CoA oxidase activities to 23% and 35%, respectively of values obtained in rats acclimated at 23 degrees C. Nafenopin treatment had no effect on IBAT wet weight, on the amounts of mitochondrial and peroxisomal proteins or on total succinate dehydrogenase activity; it resulted in a 2.9- and a 3.7-fold stimulation of the catalase and acyl CoA oxidase activities, respectively with no change in IBAT oxygen consumption. Apparent gross food efficiency was decreased to 54% of control value and colonic temperature increased by 0.91 degrees C. These results may be interpreted in the following way: nafenopin may, at 23 degrees C ambient temperature, induce an extra-heat production in other tissues than IBAT. This extra-heat production is fully compensated via the thermoregulatory feedback control. This compensation cannot occur at thermoneutrality.

Acclimatization↗
PubMed1985

Alpha- and beta-adrenergic mediation of changes in metabolism and Na/K exchange in rat brown fat.

Double- and triple-barreled ion-sensitive microelectrodes were used to measure changes in extracellular K+ and Na+ concentrations ([K+]o, [Na+]o) in brown fat. Redox states of different respiratory enzymes were measured simultaneously in order to correlate ion movements with metabolic activity. Trains of stimuli applied to the efferent nerves evoked two distinct increases in [K+]o. A first, small, rapid increase occurred within 10 s and accompanied a first, rapid membrane depolarization. A second, slow increase of [K+]o occurred several minutes after stimulation and accompanied a second, slow depolarization. A few seconds after stimulation onset, while the membrane was repolarizing and shifts in redox states indicated increases in lipolysis and respiration, [K+]o decreased. The [K+]o decrease was accompanied by an increase in [Na+]o, and could be partly blocked by ouabain. Phentolamine, an alpha-antagonist that blocks the first depolarization, also blocked the first, rapid [K+]o increase and part of the subsequent decrease. Propranolol, a beta-antagonist, had little effect on the first depolarization and the first increase in [K+]o, but blocked part of the subsequent [K+]o decrease and the second, slow [K+]o increase. The changes in [K+]o were almost completely abolished in the presence of both antagonists. It is concluded that brown adipocytes take up K+ and simultaneously lose Na+ in response to the interaction of noradrenaline with alpha- and beta-receptors, and this indicates a very early stimulation of the Na+ pump.

Adipose Tissue, Brown↗
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

Quantitative evaluation of gap junctions in rat brown adipose tissue after cold acclimation.

The decrease in the metabolic capacity of rat brown adipose tissue during the late postnatal period can be reversed by cold acclimation of the animals. In order to find out whether a parallel decrease in capability for intercellular communication observed during this period is also reversed by cold acclimation, gap junction size and number per unit area of cell surface have been quantified in freeze-fracture replicas; cell diameters have been measured in semi-thin sections. It was found that the specific number of gap junctions remains unchanged during cold acclimation. However, the mean gap junction size increases by 75% and the ratio of gap junctional area per cell volume, an index for intercellular exchange capacity, is doubled. This result illustrates further the parallelism between metabolic capacity and cell communication in brown fat.

Acclimatization↗
PubMed1983

Alpha and beta-adrenergic mediation of membrane potential changes and metabolism in rat brown adipose tissue.

Membrane potential and flavoprotein redox state have been measured simultaneously and continuously in brown adipose tissue in order to determine how nerve stimulation and adrenergic agonists control its metabolic activity. Both trains of nerve impulses and addition of noradrenaline evoke two temporally distinct cell depolarizations. The first rapid depolarization precedes the increase in flavoprotein reduction. With nerve stimulation, at the time of maximum flavoprotein reduction the cell has repolarized or hyperpolarized. The second slow depolarization follows flavoprotein reduction. Phentolamine, an alpha antagonist, selectively blocks the first depolarization, but not the flavoprotein reduction. However the time of maximum flavoprotein reduction is delayed. Propranolol, a beta antagonist, delays the first repolarization until the end of nerve stimulation and inhibits the transient hyperpolarization, second depolarization and flavoprotein reduction. Isoproterenol, a beta agonist, or the fatty acid octanoate produce only a transient hyperpolarization and subsequent slow depolarization following flavoprotein reduction. Thus brown adipose tissue contains both alpha- and beta-adrenergic receptors. Stimulation of alpha receptors produces an early membrane depolarization. Stimulation of beta receptors leads to an increase in metabolic activity which then appears to produce slow changes in membrane potential.

Adipose Tissue, Brown↗
PubMed1983

Brown adipose tissue metabolism in streptozotocin-diabetic rats.

Defects of both diet-induced thermogenesis and cold tolerance have been reported for streptozotocin-diabetic rats. Since brown adipose tissue (BAT) is a major effector of both diet- and cold-induced thermogenesis in the rat, the possible cause of these defects was investigated by comparing BAT metabolism under basal conditions and during activation by nerve stimulation, norepinephrine (NE), or octanoate addition in both streptozotocin-diabetic rats and in controls. The following metabolic indices were measured in rat interscapular BAT (IBAT): 1) tissue composition, 2) heat production rate as measured by direct microcalorimetry, 3) redox state of flavoproteins linked to the acyl-coenzyme A dehydrogenase pathway as measured by reflection spectrometry, 4) redox state of NAD(P) as measured by surface-emitted fluorescence, and 5) fatty acid activation and beta-oxidation activities in IBAT homogenate. In streptozotocin-diabetic rats, IBAT was atrophied (DNA content unmodified, protein and lipid content decreased). The basal and NE-stimulated total heat production rates showed a 75% and 56% decrease, respectively. The specific activity of fatty acid beta-oxidation as measured by flavoprotein redox state or enzymatically was decreased by 52% and 59%, respectively. The basal redox level of NAD(P) was about 3 times higher than in the controls and NE stimulation resulted in oxidation in contrast to the reduction observed in control tissues. These results show that the metabolic capacity of IBAT from streptozotocin-diabetic rats is decreased and further suggest that the reduced capacity for beta-oxidation contributes significantly to the metabolic alteration.

Adipose Tissue, Brown↗
PubMed1982

Impaired metabolic response to nerve stimulation in brown adipose tissue of hypothyroid rats.

In brown adipose tissue of the rat, chemically or surgically induced hypothyroidism caused the following effects. A large decrease of the magnitude of the metabolic response to electrical nerve stimulation. The deactivation half-time of the response was reduced to 70% of the control value, with no change in catechol O-methyltransferase activity. Pre-incubation of tissues with norepinephrine, 10(-5) M, increased the response to subsequent nerve stimulation almost to that of the controls. The catecholamine analogue dose-response curves were shifted to the right. The shift was very pronounced for isoproterenol (K50 426 nM versus 2 nM), somewhat less marked for norepinephrine (7373 nM versus 194) and very slight for phenylephrine (2803 nM versus 1649); there was almost no change in Emax values. An increase of octanoate oxidative capacity. A decrease of the capacity of the stereoselective binding of (-)-[3H]dihydroalprenolol of the high-affinity (Kd 2.0 nM) sites to a fourth of the control value and an increase by a factor of 2.9 of the Kd of the low-affinity binding sites. This decrease of binding to the beta-receptors was not sufficient quantitatively to explain the decrease in the metabolic response, suggesting the existence of an additional defective reaction which could occur between the binding to the beta-receptors and the activation of the triglyceride lipase. These results show that the sharp decrease of the metabolic response of brown adipose tissue to nerve stimulation has multiple causes. The findings are discussed in the context of the drastic decrease of cold resistance in hypothyroid rats.

Adipose Tissue, Brown↗
PubMed1982

Alterations of brown adipose tissue in genetically obese (ob/ob) mice. I. Demonstration of loss of metabolic response to nerve stimulation and catecholamines and its partial recovery after fasting or cold adaptation.

Metabolic responses to electrical nerve stimulation or norepinephrine of isolated interscapular brown adipose tissue (BAT) from lean and ob/ob mice were studied using either continuous monitoring of the NAD(P)H/NAD(P) redox state or direct microcalorimetry. The responses to these sympathetic stimuli were not significantly different from zero in BAT of ob/ob mice kept at 22 C and fed ad libitum. The metabolic rate of BAT of lean mice was stimulated 3-fold by norepinephrine. ob/ob mice are hyperglycemic and hyperinsulinemic; cold adaptation further increased their plasma glucose, and fasting decreased the levels of both glucose and insulin to normal values. Both fasting and cold adaptation at 5 C partially restored the tissue metabolic response of ob/ob mice, whereas a decreased sensitivity was observed in the tissue of lean mice. The results of these experiments are compatible with the hypothesis that the impaired capacity of BAT of ob/ob mice to produce heat could be one of the causes of their high food efficiency and their inability to withstand acute cold exposure.

Acclimatization↗
PubMed1982

Alterations of brown adipose tissue in genetically obese (ob/ob) mice. II. Studies of beta-adrenergic receptors and fatty acid degradation.

beta-Receptor number, norepinephrine-stimulated adenylate cyclase activity and lipolysis, octanoate-induced NAD(P) redox changes, and heat production were studied in brown adipose tissue (BAT) of lean and obese (ob/ob) mice. beta-Receptor number was increased 1.54-fold in purified brown adipocyte plasma membrane of ob/ob mice compared to that in lean controls. This increase was reversed by cold adaptation (5 C). Basal and norepinephrine-stimulated adenylate cyclase values were not different in the two groups. Norepinephrine stimulated lipolysis at 10 nM in BAT of lean mice, but only at 10 microM in BAT ob/ob mice. Octanoate produced an increase in the NAD(P) redox state in BAT of lean mice, but it did not modify the NAD(P) redox state in BAT of ob/ob mice. Concomitantly, octanoate increased heat production 3-fold in BAT of lean mice, but did not promote any significant increase in heat production in BAT of ob/ob mice. These two parameters were restored toward values observed in lean mice when the ob/ob mice were adapted to a cold environment. The data indicate that BAT of ob/ob mice exhibits three alterations; one at the level of the beta-receptor, one at the level of the lipolytic response to norepinephrine, and one at the level of fatty acid activation and/or beta-oxidation.

Adenylyl Cyclases↗
PubMed1982

Postnatal development of sympathetic innervation of rat brown adipose tissue reevaluated with a method allowing for monitoring flavoprotein redox state.

1. A reflection spectrometric method was developed which allowed the simultaneous measurement of flavoprotein absorption and fluorescence on an in vitro preparation of brown adipose tissue. 2. From their spectral characteristics and from the effects of substrates and a metabolic inhibitor (amytal) it was shown that the absorption and fluorescence signals are associated with different flavoproteins. 3. The fluorescence signal is mainly due to changes in the redox state of NADH dehydrogenase, and the absorption signal to changes in redox state of he flavoproteins in the acyl-CoA dehydrogenase pathway. 4. The results suggest that changes in the flavoprotein redox state in response to electrical nerve stimulation, exogenous norepinephrine and substrate addition reflect changes in the metabolic activity of the tissue. These responses were studied in the postnatal period. 5. The amplitude of the tissue response to either nerve stimulation or norepinephrine administration is already maximal at birth and decreases in animals 50 days old. The frequency of nerve stimulation of the concentration of norepinephrine required to produce a half maximum response is significantly higher for the new-born as compared to 13 day and 50 day old animals. 6. For small stimulation intensities a steady state oxidation of the NADH dehydrogenase concomitant with a steady state reduction of the flavoproteins in the acyl-CoA dehydrogenase pathway was recorded. 7. It is concluded that in rats less than 12 hours old, brown adipose tissue is functionally innervated although previous histochemical studies had failed to detect nerve terminals containing catecholamines at this early age.

Adipose Tissue, Brown↗
PubMed1981

Functional disconnection of brown adipose tissue in hypothalamic obesity in rats.

The metabolic responses to electrical nerve stimulation, norepinephrine or octanoate additions were studied using continuous monitoring of NAD(P)H/NADP redox state by reflexion spectrophotometry of interscapular brown adipose tissues from control and ventromedial hypothalamic (VMH) lesioned rats. The responses to these stimuli were all greatly decreased already 3 days after VMH lesions, indicating a reduced cell capacity to oxidize free fatty acids. Measurements of interscapular brown adipose tissue composition 4-5 weeks after VMH lesions showed a decrease of both DNA concentration and total content, indicating some tissue involution. It is concluded that the involvement of the ventromedial hypothalamus in the activation of brown adipose tissue provided a possible anatomical clue concerning pathways connecting thermal and weight regulations.

Adipose Tissue, Brown↗
PubMed1981

Is there a sympathetic regulation of the efficiency of energy utilization?

Brown adipose tissue, a well known effector of regulatory thermogenesis found in mammals, is unique in its ability to steadily increase its heat production several fold for very long periods of time. It constitutes a shunt of energy flow between food intake and heat dissipation, it is activated through its sympathetic nerve supply. There are evidence in the rat, that brown adipose tissue is activated following overfeeding, thus decreasing food efficiency and determining resistance to obesity. Genetically obese (ob/ob) mice fed and kept at 22 degrees C lack the possibility of activating their brown fat energy shunt; they are known to be poorly resistant to cold stress despite their large insulation. This is taken as a further circumstantial evidence of an overlap in thermal and food efficiency regulatory systems in rodents through sympathetically controlled brown fast as a common effector.

Adipose Tissue, Brown↗
PubMed1980

Role of glycolysis in maintenance of the action potential duration and contractile activity in isolated perfused rat heart.

1. Changing substrates from glucose to pyruvate in paced isolated rat hearts, perfused by the Langendorff technique at 65 cm H2O with a Krebs-Henseleit bicarbonate buffer, produced effects which are opposite to those of ouabain treatment: negative inotropy, decreased work efficiency, hyperpolarization, increased maximum rate of rise and amplitude of the action potential, increased conduction velocity. 2. All the effects resulting from perfusion with pyruvate can be reversed by adding ouabain at a concentration of 100 microM. 3. The correlation between various tissue metabolises and change in contractile force (delta F), rate of tension development [maximum + (dF/dt)] and rate of relaxation [maximum -(dF/dt)] was studied by multiple linear regression. No significant correlation was found with either glycogen content and tissue lactate or with cAMP and cGMP. A weak negative correlation was found with ATP and phosphocreatine. The strongest correlation was found 76 to 807 nM/g in passing from glucose- to pyruvate-containing perfusion solution. 4. In vitro tests performed with a solution containing high energy phosphates and magnesium at concentrations equal to their calculated values in the cytosol (pH 7.0) showed that a significant negative correlation exists between citrate concentration (range: 1 and 1500 M) and free calcium concentration in the micromole range. 5. It is concluded that the effects of pyruvate (non glucose substrate) perfusion could be mediated by a decrease in cytosolic-free calcium resulting from an increase in intracellular citrate. The observation that all these effects can be reversed by ouabain is taken as a circumstantial evidence of a common mechanism.

Action Potentials↗
PubMed1979

Absorption kinetics of subcutaneously injected insulin. Evidence for degradation at the injection site.

The absorption of subcutaneously injected insulin was examined by injecting semisynthetic [3H] insulin in anaesthetized pigs and subsequently analysing the tissue excised from the injection site. Contrary to previously accepted views, a significant proportion of insulin was degraded at the injection site. The disappearance of intact [3H] insulin from the injection site followed a monoexponential function with a half-time of 59 min.

Absorption↗