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Biomedical subjects

J Girard

Publications and source records attributed to J Girard.

At least 235 records · Page 13Linked to original sources

Effects of insulin and norepinephrine on glucose transport and metabolism in rat brown adipocytes. Potentiation by insulin of norepinephrine-induced glucose oxidation.

Glucose is an important fuel for rat brown adipose tissue in vivo and its utilization is highly sensitive to insulin. In this study, the different glucose metabolic pathways and their regulation by insulin and norepinephrine were examined in isolated rat brown adipocytes, using [6-14C]glucose as a tracer. Glucose utilization was stimulated for insulin concentrations in the range of 40-1000 microU/ml. Furthermore, the addition of adenosine deaminase (200 mU/ml) or adenosine (10 microM) did not alter insulin sensitivity of glucose metabolism. The major effect of insulin (1 mU/ml) was a respective 7-fold and 5-fold stimulation of lipogenesis and lactate synthesis, whereas glucose oxidation remained very low. The 5-fold stimulation of total glucose metabolism by 1 mU/ml of insulin was accompanied by an 8-fold increase in glucose transport. In the presence of norepinephrine (8 microM), total glucose metabolism was increased 2-fold. This was linked to a 7-fold increase of glucose oxidation, whereas lipogenesis was greatly inhibited (by 72%). In addition, norepinephrine alone did not modify glucose transport. The addition of insulin to adipocytes incubated with norepinephrine, induced a potentiation of glucose oxidation, while lipogenesis remained very low. In conclusion, in the presence of insulin and norepinephrine glucose is a oxidative substrate for brown adipose tissue. However the quantitative importance of glucose as oxidative fuel remains to be determined.

Adipose Tissue, Brown↗

Exclusive measurements of mean pion multiplicities in 4He-nucleus reactions from 200 to 800 MeV/nucleon.

Mean multiplicities of pi+ and pi- in 4He collisions with C, Cu, and Pb at 200, 600, and 800 MeV/u, and with C and Pb at 400 MeV/u have been measured using the large solid angle detector Diogene. The independence of pion multiplicity on projectile incident energy, target mass and proton multiplicity is studied in comparison with intra-nuclear cascade predictions. The discrepancy between experimental results and theory is pointed out and discussed.

Carbon↗

Effects of fasting on tissue glucose utilization in conscious resting rats. Major glucose-sparing effect in working muscles.

The effects of fasting on glucose metabolism in the conscious resting rat were studied. Fasting decreased whole-body glucose utilization by 40%. The fast induced a decrease in glucose utilization in muscles which are constantly working even in the resting state, i.e. heart, diaphragm and postural muscles. No modification was observed in other tissues.

Adipose Tissue↗

Regulation of fatty acid oxidation in isolated hepatocytes and liver mitochondria from newborn rabbits.

The changes in long-chain fatty acid oxidation during the first 24 h after birth were studied in isolated rabbit hepatocytes and liver mitochondria. The eightfold increase in this oxidation which occurs in hepatocytes between birth and 24 h was not triggered by a concomitant decrease in long-chain fatty acid esterification. Indeed, in isolated hepatocytes from 24-h-old rabbits, the 75% inhibition of the oxidation by 2-tetradecylglycidic acid, resulted in a total redirection of oleate metabolized towards triacylglycerol synthesis. Polarographic measurements of mitochondrial respiration showed that oxidative phosphorylation and respiratory chain capacity were fully functional at birth. By contrast, in liver mitochondria isolated from newborn rabbits, the rate of oxygen consumption from palmitoyl-L-carnitine was 60% higher than from palmitoyl-CoA. Similarly palmitoyl-CoA oxidation was increased 1.5-fold in isolated mitochondria from 24-h-old rabbits. These results were in agreement with the twofold increase in the activity of hepatic carnitine palmitoyltransferase I between birth and 24 h. However it is unlikely that the twofold increase in this enzyme activity totally explained the eightfold increase in long-chain fatty acid oxidation in isolated newborn rabbit hepatocytes. It was shown that the rate of the oxidation in isolated hepatocytes was inversely related to the rate of lipogenesis. Nevertheless, malonyl-CoA concentration per se is probably not the factor involved in the regulation of the oxidation between birth and 24 h, since a 90% decrease in hepatic malonyl-CoA concentration was not associated with a stimulation of long-chain fatty acid oxidation. The more likely mechanism was the 30-fold decrease in the sensitivity of carnitine palmitoyltransferase I to malonyl-CoA inhibition.

Animals↗

Relevance of urinary gonadotrophins.

The assay of urinary LH and FSH in first morning void urine can be used for the differential diagnosis between anorchism and bilateral cryptorchidism with impalpable testes. Furthermore, levels of urinary LH and FSH excretion and their response to intranasal stimulation with LH-RH prove helpful in the follow-up of patients under hormonal treatment, i.e. prolonged stimulation in hypogonadotrophic hypogonadism or suppression by an LH-RH analogue, for instance in precocious puberty. By increasing the sensitivity of the assay, the value of urinary gonadotrophins for the differential diagnosis and survey of hormonal treatment in very young children can be examined, and investigations of this kind are currently taking place. The method used obviously cannot assess the bioactivity of the excreted hormone, nor can it depict the pulsatility of gonadotrophin secretion.

Cryptorchidism↗

Effect of feeding a high-fat diet during pregnancy on glucose metabolism in the rat.

To alter glucose homeostasis in a period of great glucose demand, pregnant rats were submitted to a high-fat diet and compared to virgin rats. In virgin rats, blood glucose, ketone bodies, plasma insulin, and free fatty acids were not affected by the diet consumed. Glucose turnover measured in the postabsorptive period was slightly decreased in virgin rats fed a high-fat diet compared to rats fed a standard diet. Assuming that the glucose turnover rate is representative for the 24-hour average endogenous glucose production, in rats fed a standard diet the daily carbohydrate intake (9.2 +/- 0.7 g/d) exceeded the glucose turnover rate (4 +/- 0.2 g/d) and could meet the glucose requirement. In rats fed a high-fat diet the carbohydrate intake (2.7 +/- 0.2 g/d) was lower than the glucose turnover rate (3.8 +/- 0.2 g/d), which demonstrated the need for an active endogenous glucose production. Blood glucose, ketone bodies, plasma insulin, and free fatty acid concentrations followed the same patterns during pregnancy in rats fed a standard diet compared to rats fed a high-fat diet. The glucose turnover rate in the postabsorptive period was no more decreased by the high-fat diet in pregnant rats compared to virgin rats despite the greater glucose demand. In late pregnancy the glucose turnover rate was increased up to 70%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Metabolic effects induced by long-term feeding of medium-chain triglycerides in the rat.

Energy intake, weight gain, carcass composition, plasma hormones and fuels, hepatic metabolites and the activities of phosphoenolpyruvate carboxykinase (PEPCK), malic enzyme, and glucose 6-phosphate dehydrogenase (G6P-DH) were examined in adult rats during a 44-day period of low fat, high carbohydrate (LF) feeding or of consumption of one or two high (70% metabolizable energy) fat diets composed of 63% (metabolizable energy) long-chain (LCT) or medium-chain (MCT) triglycerides. Energy intake was similar in the LCT and MCT groups but was less than that of LF group. The weight gain of rats fed MCT diet was 30% less than that of rats fed LF or LCT diets. Energy retention was less when the diet provided MCT than LCT or LF, and that resulted in a 60% decrease in the daily lipids deposition. Plasma glucose, free fatty acids, glycerol, and insulin/glucagon ratio were similar in the three groups. Blood ketone body (KB) concentrations in rats fed the high fat diets were extremely elevated, particularly in the MCT group, but declined throughout the experiment and by the 44th day hyperketonemia decreased by 50% but remained higher than in the LF diet. The blood beta-hydroxybutyrate/acetoacetate (B/A) ratio remained slightly elevated in rats fed the high fat diets. Similar changes were observed in liver KB concentration and in the B/A ratio. Liver lactate/pyruvate ratio elevated in the LCT and MCT groups at the initiation of the diets decreased by 50% at the end of the experiment. The consumption of high fat diets led to a 1.5-fold increase in liver PEPCK activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A comparison of structure-activity relationships within alpha-MSH on melanophores of Anolis carolinensis and Rana pipiens.

We have compared the structure-function relationship of the tridecapeptide alpha-melanocyte stimulating hormone (alpha-MSH) on the melanophores of the lizard Anolis carolinensis and the frog Rana pipiens by determining the melanosome-dispersing potency of 15 shorter peptide sequences and 8 substituted alpha-MSH analogues. Major differences were found between the lizard and the frog in their response to alpha-MSH peptide fragments and analogues. In Anolis, the sequence Ser-Tyr-Ser- is not as important for the pigmentary response as in Rana since alpha-MSH-(4-13) was nearly as potent (89%) as alpha-MSH-(1-13) (100%), whereas in Rana alpha-MSH-(4-13) potency was reduced to 7.5%. In addition, loss of potency due to removal of residues Pro and Val was more marked in Rana (alpha-MSH-(1-11) = 0.1%) than in Anolis (alpha-MSH-(1-11) = 1%), suggesting that this C-terminal sequence is necessary for pigmentary activity in the frog melanophore. These results together with those of other peptide fragments and analogues have led us to define the minimal pigmentary sequence of alpha-MSH as alpha-MSH-(4-12) in Anolis in contrast to alpha-MSH-(1-13) in Rana. This suggests that Anolis and Rana alpha-MSH receptors recognise different message amino acids of the alpha-MSH peptide sequence even though the final response (melanosome dispersion) is the same.

Amino Acid Sequence↗

The Diogene 4 pi detector at Saturne.

Diogene, an electronic 4 pi detector, has been built and installed at the Saturne synchrotron in Saclay. The forward angular range (0 degree-6 degrees) is covered by 48 time-of-flight scintillator telescopes that provide charge identification. The trajectories of fragments emitted at larger angles are recorded in a cylindrical 0.4-m3 Pictorial Drift Chamber (PDC) surrounding the target. The PDC is inside a 1-T magnetic field; the axis of the PDC cylinder and the magnetic field are parallel to the beam. Good identification has been obtained for both positive and negative pi mesons and for hydrogen and helium isotopes. Multiplicities in relativistic nucleus-nucleus reactions up to 40 have been detected, limited mainly by the present electronics.

Elementary Particles↗

Effect of feeding pattern on the sensitivity of hepatic carnitine palmitoyl-transferase to inhibition by malonyl-CoA in the rat.

1. The feeding pattern influences the inhibitory effects of malonyl-CoA on carnitine palmitoyltransferase-I. 2. The sensitivity of liver carnitine palmitoyltransferase-I to malonyl-CoA is increased in rats meal-fed when compared to rats fed ad libitum. 3. Moreover, liver carnitine palmitoyltransferase-I of meal-fed rats remains more sensitive to inhibition by malonyl-CoA during a 24 hour fast than liver carnitine palmitoyltransferase-I of rats previously fed ad libitum.

Acyl Coenzyme A↗

alpha-MSH-induced changes in protein phosphorylation of Cloudman S91 mouse melanoma cells.

The role of protein phosphorylation in MSH-induced melanogenesis was investigated with an in vivo phosphorylation assay using intact cultured Cloudman S91 mouse melanoma cells preincubated with [32P]orthophosphate. Exposure of the cells to alpha-MSH increased the extent of labelling of two protein bands on SDS gel electrophoresis with estimated molecular weights of 43 and 34 kDa, respectively. The 32P incorporation was concentration-dependent and reached a maximal value at 10(-8) M alpha-MSH for the 43 kDa band (156% of controls) and at 10(-5) M alpha-MSH for the 34 kDa band (250% of controls). The corresponding ED50s were 5 X 10(-10) M (43 kDa) and 3 X 10(-8) M (34 kDa). The 32P incorporation into the 34 kDa band reached a maximum after a 5 min exposure to alpha-MSH whereas 43 kDa phosphorylation was maximal after a 30-60 min incubation with hormone. The effect was completely reversible after removal of the hormone and specific for melanotropic peptides. Dibutyryl cAMP (10(-3) M) and forskolin (10(-4) M) together with isobutylmethylxanthine (10(-4) M) mimicked the effect of alpha-MSH, pointing to an involvement of adenylate cyclase activation in the phosphorylation of both the 34 kDa and the 43 kDa protein. Preliminary observations showed that the 34 kDa protein is membrane-bound whereas the 43 kDa protein is of mitochondrial or melanosomal origin.

1-Methyl-3-isobutylxanthine↗

Glucose turnover rate in the lactating rat: effect of feeding a high fat diet.

Feeding a high fat diet during lactation should reduce the competition for glucose utilization between the mammary gland and the other maternal tissues, because dietary fat is directly utilized for milk lipid synthesis. Glucose homeostasis was studied in nonlactating and lactating rats fed a high fat diet and compared with that in rats fed a high carbohydrate diet. In nonlactating rats fed a high fat diet, blood glucose concentration was slightly higher, whereas plasma insulin concentration was lower than in nonlactating rats fed a high carbohydrate diet. In the postabsorptive state, plasma free fatty acids and blood ketone bodies were not modified by the nature of the diet consumed. Glucose turnover rate and glucose metabolic clearance rate in the postabsorptive state in nonlactating rats fed a high carbohydrate diet were not different from those in rats fed a high fat diet [9.5 +/- 1.4 vs. 8.8 +/- 0.8 mg/(min X kg) and 8.9 +/- 1.2 vs. 7.9 +/- 0.7 mL/(min X kg)]. In lactating rats, blood glucose and ketone bodies, plasma insulin and free fatty acid concentrations were not affected in the postabsorptive state by the composition of the diet consumed. The glucose metabolic clearance rate in lactating rats fed the high carbohydrate diet was higher than that in nonlactating rats fed the same diet. However, the glucose metabolic clearance rate in lactating rats fed the high fat diet was not different from that in nonlactating rats fed the same diet.

Animals↗

Pregnancy-induced insulin resistance in liver and skeletal muscles of the conscious rabbit.

Insulin sensitivity of maternal nonuterine tissues (liver and skeletal muscles) has been investigated in the conscious rabbit during late gestation (24 and 30 days). The specific effect of insulin on glucose production and utilization was evaluated with the hyperinsulinemic euglycemic clamp technique. The net balance of glucose across the hindlimb muscles was studied by means of the Fick principle in basal and insulin stimulated conditions (clamp study). Our results show that an insulin-resistant state develops between days 24 and 30 of gestation in the rabbit and involves both glucose producing (liver) and utilizing (muscles) tissues. On day 30 of gestation, muscle glucose uptake was not significantly stimulated at a plasma insulin concentration of 700 microU/ml, whereas it was stimulated by 30-40% in nonpregnant and 24 day pregnant rabbits. At similar plasma insulin concentration, endogenous glucose production was suppressed by 85% in both nonpregnant and 24 day pregnant rabbits, whereas it was decreased by only 30% in 30 day pregnant rabbits. The present data suggest that hindlimb muscles of late pregnant rabbits are able to reduce their insulin-induced glucose utilization. This could contribute to meet the glucose requirements of pregnant uterus in late gestation.

Animals↗

Effect of insulin on in vivo glucose utilization in individual tissues of anesthetized lactating rats.

Glucose utilization rate has been measured in skeletal muscles, white adipose tissue, and mammary gland of anesthetized nonlactating and lactating rats. During lactation, basal glucose utilization is decreased by 40% in periovarian white adipose tissue and by 65% in epitrochlearis and extensor digitorum longus but not in soleus muscle. This may be related to the lower blood glucose and plasma insulin concentrations observed during lactation. Basal glucose utilization rate in the mammary gland was, respectively, 18 +/- 2 and 350 +/- 50 micrograms/min in nonlactating and lactating rats. During the euglycemic hyperinsulinemic clamp, a physiological increment in plasma insulin concentration (231 +/- 18 in lactating vs. 306 +/- 24 microU/ml in nonlactating rats) induces a similar increase in glucose utilization rate in skeletal muscles (except soleus) and white adipose tissue in the two groups of rats. Furthermore this low increase in plasma insulin concentration does not alter mammary glucose utilization rate in nonlactating rats but induces the same increase (sevenfold over basal) as a maximal insulin concentration in lactating rats. These data show that the active mammary gland is the most insulin-sensitive tissue of the lactating rat that has been tested. The overall increase in insulin sensitivity and responsiveness that has been described in lactating rats can then mainly be attributed to the presence of the active mammary gland.

Absorption↗

Effect of anesthesia on glucose production and utilization in rats.

This study was undertaken to determine the effects of pentobarbital anesthesia (50 mg/kg ip) on glucose kinetics and individual tissue glucose utilization in vivo, in chronically catheterized rats. Glucose turnover studies were carried out using [3-3H]glucose as tracer. A transient hyperglycemia and an increased glucose production were observed 3 min after induction of anesthesia. However, 40 min after induction of anesthesia, glycemia returned to the level observed in awake animals, whereas glucose turnover was decreased by 30% as compared with unanesthetized rats. These results are discussed with regard to the variations observed in plasma insulin, glucagon, and catecholamine levels. Glucose utilization by individual tissues was studied by the 2-[1-3H]deoxyglucose technique. A four- to fivefold decrease in glucose utilization was observed in postural muscles (soleus and adductor longus), while in other nonpostural muscles (epitrochlearis, tibialis anterior, extensor digitorum longus, and diaphragm) and other tissues (white and brown adipose tissues) anesthesia did not modify the rate of glucose utilization. A decrease in glucose utilization was also observed in the brain.

Animals↗

Insulin resistance during suckling period in rats.

Glucose metabolism was studied in 13- to 15-day-old suckling rats and 28- to 30-day-old rats weaned at 19 days on a high-carbohydrate, low-fat diet. The glucose turnover rate in the basal state was similar in suckling and weaned rats (14 mg X min-1 X kg-1). Glucose infusion (20 mg X min-1 X kg-1) produced a moderate hyperglycemia in weaned rats (150 mg/dl), whereas the suckling rats developed a high hyperglycemia (280 mg/dl), despite a large increase of plasma insulin concentration. The effect of insulin on glucose kinetics was then assessed by the euglycemic-hyperinsulinemic clamp technique. The plasma insulin levels reached were 736 +/- 87 microU/ml in the suckling and 444 +/- 34 microU/ml in the weaned rats, despite similar insulin infusion rates. Hepatic glucose production was suppressed by 90% in the weaned rats, whereas it remained at 40% of basal value in the suckling rats. The increase of glucose utilization above basal was fourfold higher in the weaned than in the suckling rats. Thus an insulin resistance state is present in the suckling rats and disappears after weaning onto a high-carbohydrate diet.

Animals↗

Hyperglycemia and hyperinsulinemia increase glucose utilization in fetal rat tissues.

In vivo measurement of glucose utilization by individual tissues of 19-day rat fetuses have been performed using radioactive 2-deoxy-D-glucose technique. In the basal state, glucose metabolic index was 13.6 +/- 0.5 ng.min-1.mg-1 for the whole fetus, 21 +/- 1 in the hindlimb muscles, 13 +/- 2 in the liver, and 16 +/- 2 in the brain, whereas the fetal heart had the highest value: 62 +/- 5 ng.min-1.mg-1. To raise the fetal glycemia, the basal maternal blood glucose concentration of 0.78 +/- 0.02 g/l was elevated to 1.04 +/- 0.02 g/l by mean of hyperglycemic clamps. The fetal hyperglycemia increased glucose metabolic index by 30-100% over basal values in all the tissues tested except in the brain. To raise fetal insulinemia, maternal euglycemic clamp with supraphysiological insulin concentrations were performed, then a fraction (1%) of exogenous insulin crossed the placenta. Fetal plasma insulin concentrations were thus elevated to 180 +/- 32 and 255 +/- 23 microU/ml. The fetal heart increased significantly its glucose metabolic index in response to the lower insulin level. Glucose metabolic index in hindlimb muscles and liver was increased by 50-100% for the highest insulin level, whereas the brain was unaffected by exogenous insulin. We conclude that glucose metabolic index is stimulated by physiological hyperglycemia in individual fetal tissues and that fetal tissues (heart, liver, and muscle) are sensitive to exogenous insulin.

Animals↗