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Biomedical subjects

B Jeanrenaud

Publications and source records attributed to B Jeanrenaud.

At least 91 records · Page 5Linked to original sources
PubMed1989

In vivo response of microfabricated glucose sensors to glycemia changes in normal rats.

A planar glucose sensor based on an amperometric detection of H2O2 is presented. The transducer part which is a planar three-electrode cell consisting of two Pt-electrodes and one Ag/AgCl-thin film electrode is realized using microelectronic technology. The overall dimensions are 0.8 mm x 3 mm x 0.38 mm and the working electrode area is 0.1 mm2. GOD is immobilized using glutaraldehyde as a cross-linking agent and bovine serum albumin as a carrier protein. The resulting membrane has a typical thickness of 25 microns. Also, an outer polyurethane membrane is dip-coated all around the tip of the electrode. The influence of pO2 on the sensor response as well as the sensor temperature coefficient, sensitivity and linear range have been investigated. The sensor has been tested in vivo in a subcutaneous tissue of anaesthetised rats. During experiments, blood sampling allows to measure changes in venous plasma glucose using a Beckman analyzer. The sensor response following hyperglycaemic clamps as well as intravenous glucose loads is discussed.

Animals↗
PubMed1988

Hyperinsulinemia of the genetically obese (fa/fa) rat is decreased by a low dose of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT).

Changes in glycemia and insulinemia were determined in conscious lean (FA/?) and obese (fa/fa) rats after acute administration of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). The intravenous injection of a low dose of 8-OH-DPAT (150 micrograms/kg) to lean rats rapidly promoted hyperglycemia. This modification was associated with a slight increase in insulinemia. The injection of 8-OH-DPAT markedly decreased basal hyperinsulinemia in obese rats while inducing hyperglycemia. Further evidence of the strong inhibitory effect of 8-OH-DPAT on insulin release was obtained in lean and obese rats during glucose tolerance tests. Intracerebroventricular injection of 8-OH-DPAT (45 micrograms/animal) triggered hyperglycemia and markedly decreased insulinemia in both lean and obese rats. This hypoinsulinemic effect of 8-OH-DPAT was more pronounced in the obese than in the lean animals. Measurement of the food intake elicited by 8-OH-DPAT (500 micrograms/kg s.c.) showed that the hyperphagic action of the 5-HT1A agonist was the same in FA/? and fa/fa rats. It is suggested that: (i) hyperinsulinemia of the genetically obese rat may be diminished by a low dose of 8-OH-DPAT; (ii) 5-HT1A autoreceptor-mediated regulation of serotonergic activity is not different in lean (FA/?) and obese (fa/fa) rats; (iii) 8-OH-DPAT could be of potential therapeutic use for some aspects of the pathology of type II diabetes.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
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↗
PubMed1988

Abnormal regulation of pancreatic glucagon secretion in obese fa/fa rats.

The results reported in the literature regarding glucagonaemia in genetically obese fa/fa rats are conflicting: normal, increased or decreased plasma glucagon levels have been reported. Due to the existence of several molecules endowed with glucagon-like immunoreactivity, it was thought that the conflicting data could be related to the degree of specificity of the different glucagon antibodies. Three antibodies that all qualified as being specific for pancreatic glucagon were used. It was found that, depending on the antibody, absolute values of basal glucagonaemia or arginine-induced glucagon output varied quantitatively and qualitatively in both lean and obese rats. When non-extracted basal or stimulated plasma samples were passed on a G-50 Sephadex column, glucagon-like immunoreactivity was present over a wide range of molecular weights, indicating the presence of non-pancreatic glucagon molecules. When an ethanol extraction was used, the fractions eluting from the G-50 Sephadex column contained only pancreatic glucagon immunoreactivity. It is concluded that ethanol extraction is necessary for the measurement of the 3500 daltons glucagon. Using this methodology it was found that: (1) basal glucagonaemia was low but identical in the two groups of rats; (2) arginine-induced glucagon secretion was greater in obese than in lean animals; (3) glucagonaemia was decreased by glucose administration in lean but not in obese rats. It is concluded that there are, in obese animals, dysfunctions of glucagon output that may play a role in their abnormal glucose tolerance.

Animals↗
PubMed1988

Heart glucose transport and transporters in rat heart: regulation by insulin, workload and glucose.

Aspects of the regulation of the glucose transport by perfused hearts of normal rats have been studied by measuring glucose transport (via the efflux of labelled 3-O-methyl-D-glucose) and glucose transporters (via the labelled cytochalasin B binding assay). Similarly to what is observed with insulin, increasing workload (by raising perfusion pressure from 50 to 100 mm Hg) stimulated glucose transport 7 to 8-fold. Glucose (via its analog 3-O-methylglucose, used at 15 mmol/l) stimulated its own transport 4-fold. The three stimuli favored the translocation of glucose transporters from an intracellular pool (microsomes) to the plasma membrane. Insulin increased the apparent affinity (decreased dissociation constant values) of plasma membrane transporters for cytochalasin, as well as the Hill coefficient, indicating the occurrence of a positive cooperativity amongst plasma membrane transporters. Workload increased only the Hill coefficient, glucose only the apparent affinity for cytochalasin of plasma membrane transporters. This study shows that insulin, workload and glucose itself stimulate glucose transport by favouring the translocation process of glucose transporter as well as by changing, albeit by a different mechanism, the functional properties of the transporters once translocated to the plasma membrane.

3-O-Methylglucose↗
PubMed1988

Effect of electrical stimulation of the vagus nerve on insulinemia and glycemia in Acomys cahirinus mice.

To investigate the parasympathetic regulation of the endocrine pancreas in spiny mice (Acomys cahirinus), unilateral electrical stimulations of the left cervical vagus nerve were performed in these animals and their controls, the albino mice. Plasma insulin and glucose levels were measured before and after the stimulation. The stimulation parameters were: 2-2.5 V, 14 Hz, 1 msec for the albino mice and 3 V, 14 Hz, 1 msec or 15-20 V, 20 Hz, 1 msec for the spiny mice. Already 2 min after the start of the stimulation, the acomys as well as the albino mice showed a significant increase in plasma insulin levels which was accompanied by a weak but significant increase in glycemia. However, the total insulin output in the acomys mice was half than that of the albino mice. Carbachol administration had no effect on insulin secretion in the acomys mice, while it increased that of the controls. Atropine pretreatment failed to abolish the insulin release elicited by electrical stimulation of the vagus nerve in the acomys mice, while it abolished it in the albino ones. It is proposed that the vagus-nerve mediated insulin release that is present in the acomys mice is exerted, not via muscarinic receptors as in controls, but possibly via other neurotransmitter(s).

Animals↗
PubMed1988

Taste-induced changes in plasma insulin and glucose turnover in lean and genetically obese rats.

Cephalic-phase insulin release (CPIR) and the changes in glucose turnover induced by saccharin ingestion were studied in freely moving lean and genetically obese fa/fa rats equipped with chronic catheters for blood sampling. Six-hour-fasted lean and obese rats were trained to drink 1 ml sodium saccharin (0.15%) or 1 ml glucose (70%), and blood samples were taken before and after the stimuli. As early as 1-1.5 min poststimulus, there was a significant increase in CPIR in lean and obese rats. The amplitude of the CPIR induced either by saccharin or by glucose in the obese rats was significantly higher than it was in the lean rats. The effect of saccharin ingestion on the hepatic glucose production (HGP) and the rate of glucose disappearance (Rd) was studied in 6-h-fasted lean and obese rats, under non-steady-state conditions, according to a method previously validated. Saccharin ingestion produced a significant increase in HGP and Rd in lean and obese rats compared with basal values. The saccharin-induced increments in HGP and Rd were higher in the obese than in the lean animals. We conclude that saccharin (through taste) appears to elicit parasympathetic (insulin release) and sympathetic (HGP increase) reflexes in lean and obese rats. These taste-induced changes in plasma insulin and glucose turnover are exaggerated in the obese rats and may participate in obesity and in insulin resistance of the overall syndrome.

Animals↗
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↗
PubMed1987

The onset of liver glycogen synthesis in fasted-refed lean and genetically obese (fa/fa) rats.

Lean and genetically obese (fa/fa) rats were fed ad libitum, or fasted for 17 h and then meal-fed for varying time intervals. During refeeding, glucose-6-phosphatase activity of lean rats declined to the low value that was present in livers of fasted obese rats and which remained unchanged in the obese group during the meal. Refeeding also resulted in increases in hepatic concentrations of glucose-6-phosphate and fructose-6-phosphate, fructose 1,6-bisphosphate, fructose-2,6-bisphosphate, alpha-glycerophosphate, pyruvate and lactate in lean and obese rats, absolute values being higher in the fasted obese than in the fasted lean group. Obese animals had higher postprandial portal blood insulin, glucose and lactate concentrations than lean animals. In spite of this, the rate of hepatic glycogen deposition was the same in both groups and was accompanied by similar glycogen synthase a levels. Following refeeding, phosphorylase was transiently inactivated in livers of lean but not of obese animals, while glycogen synthase was inactivated in both groups. The data suggest that in lean animals refeeding was associated with a stimulation of liver glycolysis, presumably by insulin; in fasted obese rats hepatic glycolysis was already in a stimulated state and was only slightly enhanced further after the meal, in keeping with their unaltered hyperinsulinaemia; there was an increased turnover of liver glycogen or a resistance to insulin stimulation of glycogen synthesis in fa/fa rats during refeeding.

Animals↗
PubMed1987

Non-steady-state measurement of glucose turnover in rats by using a one-compartment model.

One of the tracer methods often employed to measure glucose turnover in the non-steady state uses the one compartment model of Steele (Ann. NY Acad Sci 1959). However, this model gives adequate results when it is assumed that only a fraction of the glucose pool takes part in rapid changes of glucose specific activity, thereby being necessary to use a correction factor called the "pool fraction." The aim of this study was to experimentally determine the best pool fraction needed in the rat for the calculation of glucose turnover using a one-compartment model. This is important as no data are available so far in this widely used species. For this purpose, glucose turnover was measured in anesthetized lean and genetically obese fa/fa rats, using two different experimental designs. In all conditions, the error in estimating the total rate of glucose appearance was lowest when 0.5 was used as the pool fraction. The error was greater with an increase and a decrease in the pool fraction value. It is concluded that in the rat the one-compartment model measures changes in glucose turnover with reasonable accuracy in non-steady-state conditions and that a pool fraction of 0.5 gives the best results.

Animals↗
PubMed1987

Identification of a major defect in insulin-resistant tissues of genetically obese (fa/fa) rats. Impaired protein kinase C.

In perfused lean rat hearts, the activator of protein kinase C phorbol myristate acetate (PMA), when present alone, stimulates glucose transport but inhibits the insulin stimulation of this transport. PMA also inactivates glycogen synthase in hepatocytes. In contrast, none of these effects are observed in hearts and hepatocytes of obese animals, indicating an impaired protein kinase C activation in these tissues, which are insulin resistant. Direct measurements of protein kinase C activity in lean rat hearts revealed that PMA provokes a translocation of the enzyme from a soluble to a particulate fraction. In obese rat hearts, the basal distribution of protein kinase C is altered (more activity is found in the soluble and less in the particulate fraction), and the translocation induced by PMA is impaired. Pretreatment of lean rats with PMA in vivo, aimed at downregulating protein kinase C, induces the same defects (i.e., insulin resistance and unresponsiveness to PMA) as those observed in hearts of untreated obese animals. The results indicate that part of the insulin resistance might be the consequence of altered modulation of insulin action by protein kinase C.

3-O-Methylglucose↗
PubMed1987

Development of obesity in Zucker rats. Early insulin resistance in muscles but normal sensitivity in white adipose tissue.

Euglycemic-hyperinsulinemic clamps were performed on 4- and 12-wk-old anesthetized lean and obese Zucker rats. During the clamp studies, total glucose production and utilization were assessed with a 3-[3H]glucose perfusion, whereas local glucose utilization was determined by measuring 2-deoxy-1-[3H]glucose 6-phosphate accumulation in various tissues. In the basal state, 4 wk-old obese rats were hyperinsulinemic (159 +/- 8 vs. 82 +/- 9 microU/ml), whereas glucose turnover rate was similar to that observed in lean rats (14.9 +/- 1.9 vs. 12.5 +/- 1.9 mg X min-1 X kg-1). Glucose utilization was identical in skeletal muscles, whereas it was increased in white adipose tissue of obese rats (22 +/- 4 vs. 8 +/- 2 ng X min-1 X mg-1). At plasma insulin level of 500 microU/ml, glucose production was totally suppressed in both groups, whereas overall glucose utilization was slightly less in 4-wk-old obese than in lean rats. This was due to a reduced stimulation of glucose utilization in skeletal muscles and brown adipose tissue. In contrast, glucose utilization in periovarian white adipose tissue was similarly increased in lean and obese rats. For a maximal insulin concentration (1500 microU/ml), all the differences were abolished between lean and obese young Zucker rats. In older (12-wk-old) obese rats, glucose utilization in various tissues was markedly reduced at maximal insulin level compared with that observed in age-matched lean animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗