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B Jeanrenaud

Publications and source records attributed to B Jeanrenaud.

At least 109 records · Page 6Linked to original sources
PubMed1987

Role of the oropharynx in regulation of glycemia.

Previous studies have demonstrated that reflexes originating from the oral cavity at the start of food intake are necessary to ensure a normal glucose tolerance. In our experiment, the underlying mechanisms of these reflexes were studied in conscious, freely moving rats bearing chronic catheters. A double-isotope technique was used to measure, under non-steady-state conditions, rates of total glucose appearance (total Ra), total glucose disappearance (Rd), gut glucose absorption (gut Ra), hepatic glucose production (HGP), and the metabolic clearance rate of glucose (MCRg). In random order, 1 wk apart, rats either spontaneously drank 1 ml of a 60% glucose solution or were given the same dose into the stomach via a chronic gastric catheter. Glycemia and insulinemia were lower when glucose was taken orally than when the same amount of the substrate was administered intragastrically. Total Ra after glucose administration was the same in both groups throughout the experiment. Despite lower insulin and glucose values, the increase in Rd was initially higher in the oral group than in the intragastric group. This was accompanied by initial higher MCRg values in the oral group than in animals that received the glucose load directly into their stomachs. We conclude that a series of reflexes elicited by oral glucose ingestion improve glucose tolerance by increasing the efficiency of glucose disposal in the early stages after a glucose load, with a smaller amount of insulin released.

Animals↗
PubMed1987

5-HT1A and alpha-2 adrenergic receptors mediate the hyperglycemic and hypoinsulinemic effects of 8-hydroxy-2-(di-n-propylamino)tetralin in the conscious rat.

The ability of the 5-hydroxytryptamine (5-HT)1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) to affect plasma glucose levels and insulin release was assessed in rats bearing chronic jugular catheters. The i.v. administration of 8-OH-DPAT (150 micrograms/kg) rapidly promoted a transient hyperglycemia. Despite high glucose levels, insulinemia remained constant. Dose-response curves revealed that maximal hyperglycemia was associated with hypoinsulinemia. Increased glycemia, which was also found to be induced by other 5-HT direct and indirect agonists, lasted longer in food-deprived rats. Evidence for a strong inhibitory effect of 8-OH-DPAT on insulin release was reported in rats submitted to i.v. glucose tolerance tests. Pretreatments with the dopaminergic blocker haloperidol, the alpha-1 adrenoceptor antagonist prazosin or the 5-HT2 blocker ketanserin were ineffective. In contrast, the alpha-2 adrenoceptor antagonist idazoxan and the unspecific 5-HT antagonist methiotepin prevented the hyperglycemic and the hypoinsulinemic effects of 8-OH-DPAT. Blockade of these changes by (-)-propranolol (a 5-HT1 blocker), but not by (+)-propranolol, indicated that 5-HT1 and alpha-2 adrenergic receptors mediated 8-OH-DPAT-induced hyperglycemia. Reserpine pretreatment did not prevent the effects of 8-OH-DPAT. Central injection of 8-OH-DPAT induced hyperglycemia, the amplitude of which was equivalent to that measured after i.v. administration. Selective degeneration of serotonergic nerve cells by 5,7-dihydroxytryptamine did not prevent 8-OH-DPAT-induced alterations, thus rendering a key role for presynaptic mechanisms unlikely.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1987

[Interactions between the central nervous system, the endocrine pancreas and metabolism].

1. The importance of nervous circuits including neural afferences, their integration by the central nervous system and the resulting efferents is illustrated by comparing glucose tolerance following the spontaneous ingestion or the intragastric administration of a glucose load. When these circuits are by-passed (intragastric glucose administration), glucose tolerance is impaired and accompanied by an increased insulin output compared to the situation of normal glucose ingestion. This is due to a decreased glucose utilization in the absence of the numerous reflexes that are elicited by the presence of glucose in the oropharynx. 2. In normal animals, insulin secretion by the B cell of the endocrine pancreas is under an inhibitory tonus by the sympathetic nervous system while the parasympathetic system has no stimulatory tonus. After acute bilateral destruction of the ventromedial hypothalamic nuclei (VMH), such a situation is reversed and there is an activation of the parasympathetic outflow leading to hyperinsulinemia. This hyperinsulinemia is partly responsible for the development of the obesity of VMH-lesioned animals and is accompanied by a decreased activity of some sympathetic efferents amongst which those innervating brown adipose tissue. Analogous data have been obtained when studying genetically obese fa/fa rats. 3. A peptide of around 1'000 daltons extracted from the rat hypothalamus and having insulin secretion promoting activity could possibly be an insulin-releasing factor since it is present not only in the hypothalamus but also in the plasma.

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

Glucose utilization in vivo and insulin-sensitivity of rat brown adipose tissue in various physiological and pathological conditions.

Brown-adipose-tissue glucose utilization rate and its insulin-sensitivity were measured in vivo in the anaesthetized rat by a 2-deoxy[1-3H]glucose technique. Glucose utilization can be increased 60-fold by insulin, to reach extremely high rates. Glucose utilization and its insulin-sensitivity are modulated in accordance with physiological or pathological conditions.

Adipose Tissue, Brown↗
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

In vivo metabolic changes as studied longitudinally after ventromedial hypothalamic lesions.

Ventromedial hypothalamic (VMH)-lesioned rats were tested 1 and 6 wk after the lesions to determine, by euglycemic-hyperinsulinemic clamps, their tissue response to insulin. One week after the lesions, total glucose metabolism was more sensitive and responsive to insulin than in age-matched controls. In the two groups, hepatic glucose production was suppressed at almost identical insulin concentrations (approximately 550 microU/ml). Six weeks after the VMH lesions, the increased insulin responsiveness of total glucose metabolism disappeared and glucose metabolism became less insulin sensitive (right, shifted dose-response curve) than that of control animals. Furthermore, hepatic glucose production of VMH-lesioned rats was now inhibited by 45% at most and at the supraphysiological insulin concentration of 16,000 microU/ml, while it was totally suppressed by 550 microU/ml of the hormone in age-matched controls. This defect was accompanied by a lack of decrease in plasma glucagon levels during the clamps carried out at maximal insulin concentration. In summary, in a first phase after VMH lesion, rats are hypersensitive and hyperresponsive to insulin; and in a later phase, when obesity is well established, VMH-lesioned rats become insulin resistant and are characterized by a decreased in vivo sensitivity and responsiveness of liver and muscles to 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↗
PubMed1986

Mechanism of abnormal oral glucose tolerance of genetically obese fa/fa rats.

The genetically obese fa/fa rat is glucose intolerant when tested in a conscious state after the spontaneous ingestion of a glucose solution. The aim of this study was to investigate the mechanism(s) underlying the abnormal oral glucose tolerance test of obese animals with the non-steady-state measurement of glucose turnover proposed by Steele et al. in 1968. Our results show that the total rate of glucose appearance is enhanced in obese compared with lean animals. This abnormality is not due to an increased gut glucose absorption but to a lack of suppression and even a transient stimulation of hepatic glucose production after the ingestion of glucose. The rate of glucose utilization by the obese animals is somewhat increased compared with controls or unchanged when expressed as glucose metabolic clearance rate, thus excluding this parameter from the factors contributing to the observed glucose intolerance. The results obtained with genetically obese rats agree with those reported for type II diabetes in humans. The observed defect of the obese group could be related to an abnormal regulation of insulin counterregulatory hormone(s) or of hepatic innervation as well as to other defects of hepatic glycogen handling.

Animals↗
PubMed1985

Control of glycogen phosphorylase interconversion by phorbol esters, diacylglycerols, Ca2+ and hormones in isolated rat hepatocytes.

In isolated rat hepatocytes: phosphorylase activation by the ionophore A23187 was enhanced in the presence of tumour-promoting phorbol esters and 1,2- (but not 1,3-) diacylglycerols (dioleoyl- and oleoylacetyl-glycerol), with a similar dose-dependency; the activation of phosphorylase by phenylephrine (1 microM) (but not by vasopressin or glucagon) was inhibited both by tumour-promoting phorbol esters and diacylglycerols, but with a different dose-dependency: complete inhibition was achieved with concentrations of phorbol esters two orders of magnitude lower than those of diacylglycerol; binding of the alpha 1-adrenergic antagonist [3H]prazosin and its displacement by unlabelled prazosin was not significantly affected in the presence of the phorbol esters. The possible involvement of protein kinase C in the control of phosphorylase interconversion is discussed.

Animals↗
PubMed1985

Tumour-promoting phorbol esters increase basal and inhibit insulin-stimulated lipogenesis in rat adipocytes without decreasing insulin binding.

In isolated rat adipocytes, tumour-promoting phorbol esters caused (1) dose-dependent stimulation of lipogenesis in the absence of insulin and (2) inhibition of the lipogenic effect of submaximal concentrations of insulin, but without affecting insulin binding. The possible involvement of protein kinase C in insulin action is discussed.

Adipose Tissue↗
PubMed1985

Insulin: its relationship to the central nervous system and to the control of food intake and body weight.

This article describes the close relationship among the hormone insulin, the central nervous system, and the regulation of food intake and body adiposity. The initial section documents the control of insulin output from the pancreas by the central nervous system, and a later section describes the relationship of insulin levels in the blood to the degree of adiposity. Another section documents the ability of insulin to gain access to the brain and to elicit responses there. Finally, the behavioral effects of insulin added to the brain, and especially its ability to reduce food intake and body weight, is discussed. The implications to obesity are stressed throughout.

Adipose Tissue↗
PubMed1985

Abnormal oral glucose tolerance in genetically obese (fa/fa) rats.

The effect of intravenous glucose or tolbutamide administration on plasma glucose and insulin levels was compared with that following spontaneous ingestion of glucose in freely moving 6- to 7-wk- and 13- to 14-wk-old lean and obese (fa/fa) rats. Irrespective of age, the obese rats had a normal blood glucose tolerance when glucose or tolbutamide load was given intravenously, whereas the glucose ingestion [oral glucose tolerance test (OGTT) caused a marked glucose intolerance that became more pronounced with the duration of the syndrome. This suggests that factors other than insulin resistance could play a role in the occurrence of abnormal OGTT in obese rats. When blood insulin levels were expressed as percent change over base line and when compared with age-matched normal rats, the 6- to 7-wk obese rats showed a normal and even higher beta-cell responsiveness to intravenous or oral glucose as well as to tolbutamide. In contrast, the 13- to 14-wk obese rats presented a decreased beta-cell responsiveness to all such stimuli. Thus the beta-cell function of obese rats worsens with time. Inasmuch as 13- to 14-wk-old obese fa/fa rats have insulin resistance, high basal glycemia, and abnormal oral glucose tolerance, they can be viewed as a potential model of type II diabetes.

Age Factors↗
PubMed1985

Involvement of the cholinergic system in insulin and glucagon oversecretion of genetic preobesity.

The etiology of the abnormal secretion of hormones from the endocrine pancreas of genetically obese (fa/fa) rats is unknown. In this study, we tested the postulate that there is an early occurrence of increased efferent parasympathetic activity to the endocrine pancreas of these rodents. Unweaned female 17-day-old pups were anesthetized and tested by an iv bolus of arginine to stimulate insulin and glucagon output. At the time of the tests, pups were indistinguishable from each other. They were, therefore, kept to adulthood to allow for their separation into an obese (25% of total animals) and a lean (75%) group. Those animals that became obese were retrospectively referred to as preobese. Basal insulinemia and glucagonemia were identical in the two groups, as were the dynamics of arginine-induced hormone release. However, arginine-induced insulin as well as glucagon output were higher in preobese than in lean pups. These two abnormalities were abolished by acute atropine pretreatment. It is concluded that the substrate-induced insulin and glucagon oversecretion of preobese pups is an early defect that is mediated via the vagus nerve.

Age Factors↗