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B Jeanrenaud

Publications and source records attributed to B Jeanrenaud.

At least 163 records · Page 9Linked to original sources
PubMed1982

Effect of rat hypothalamic extract administration on insulin secretion in vivo.

Supernatants obtained from extracts of both the ventrolateral (VLH) and ventromedial (VMH) hypothalamus of normal rats were found to promote insulin secretion when injected in vivo to normal rats. Catecholamines, acetylcholine, and enkephalins can be excluded as potential candidates in producing the effects of VLH extract administration, since pretreatment of recipient rats with their respective specific blockers (i.e. phentolamine, propranolol, atropine, and naloxone) did not prevent the increase in plasma insulin levels observed after the injection of VLH extracts. In contrast, atropine and propranolol reduced by about 50% the rise in plasma insulin levels that followed the injection of VMH extracts. When extracts of VLH or VMH were partially purified, the insulin-releasing activity was found to correspond, in both cases, to compounds of low molecular weight (i.e. 3600 or lower). Furthermore, digestion of partially purified VLH extracts with trypsin or collagenase markedly decreased their in vivo insulin-promoting activity, suggesting a possible polypeptidic nature of the factor(s) involved. The presence of hypothalamic factor(s), which may conceivably be involved in physiological regulation of insulin secretion, is therefore suggested. This is in keeping with analogous results obtained by other laboratories using different species and experimental conditions.

Animals↗
PubMed1982

Brain stem infusion of the gamma-aminobutyric acid antagonist bicuculline increases plasma insulin levels in the rat.

Previous neuroanatomical and physiological studies have indicated that nucleus ambiguus (Amb) is one source of vagal motoneurons in the brain stem that innervates the pancreas and which, when stimulated, increases insulin release. To investigate one of the neurotransmitter inputs to Amb neurons and its relation to insulin secretion, bicuculline, a specific gamma-aminobutyric acid (GABA) antagonist, was infused bilaterally into the Amb region as well as into a neighboring area, the rostral level of the lateral nucleus tractus solitarius (nts) of anesthetized male rats. Experiments were carried out in the presence or absence of the alpha-adrenergic blocker phentolamine. In the absence of phentolamine, no increases in plasma insulin levels were seen after bicuculline or vehicle infusion into the Amb region or after bicuculline infusion into the nts, while plasma glucose levels were significantly increased. In the presence of phentolamine, bicuculline infusion into the Amb region led to a prompt and significant increase in plasma insulin levels that could not be accounted for by changes in glycemia. The infusion of vehicle into Amb or of bicuculline into nts produced small or insignificant increases in plasma insulin levels. These results suggest that Amb neurons capable of modulating plasma insulin levels are under tonic GABA inhibition, an effect that appears to be specific for Amb neurons, since bicuculline infusion into another brain stem nucleus (nts) had no effect on insulin release. The fact that phentolamine pretreatment was necessary to reveal the bicuculline-induced effects corroborates previous studies showing that in addition to a central nervous system inhibition of vagal motoneurons by GABA, there is a tonic sympathetic inhibitory input to the endocrine pancreas capable of masking any disinhibition of vagal motoneurons. The physiological role of GABA inhibition of Amb neurons that innervate the pancreatic beta-cells remains to be determined.

Animals↗
PubMed1982

Possible role of the CNS in regulating insulin secretion via humoral factors.

Among the several possible mechanisms responsible for hyperinsulinemia of obese rodents, an abnormal CNS-endocrine pancreas axis has been postulated. This axis appears to involve neural (parasympathetic, sympathetic) relationships. A humoral link between the CNS and the pancreas could also exist, as based on data from these and other laboratories. Indeed, CNS sites such as the ventrolateral, the ventromedial hypothalamus or the neurointermediate lobe of the pituitary, have been shown to contain substances possessing insulin secretion modulating activity. The precise nature of these substances has yet to be determined, as well as their ability to actually be released into the systemic circulation.

Animals↗
PubMed1981

Stimulation of hepatic lipogenesis and acetyl-coenzyme A carboxylase by vasopressin.

The effect of vasopressin on the short-term regulation of fatty acid synthesis was studied in isolated hepatocytes from rats fed ad libitum. Vasopressin stimulates fatty acid synthesis by 30-110%. This increase is comparable with that obtained with insulin. Angiotensin also stimulates fatty acid synthesis, whereas phenylephrine does not. The dose-response curve for vasopressin-stimulated lipogenesis is similar to the dose-response curve for glycogenolysis and release of lactate plus pyruvate. Vasopression also stimulates acetyl-CoA carboxylase activity in a dose-dependent manner. Vasopressin does not relieve glucagon-inhibited lipogenesis, whereas insulin does. The action of vasopressin on hepatic lipogenesis is decreased, but not suppressed, in Ca2+-depleted hepatocytes. The results suggest that vasopressin acts on lipogenesis by increasing availability of lipogenic substrate (lactate + pyruvate) and by activating acetyl-CoA carboxylase.

Acetyl-CoA Carboxylase↗
PubMed1981

Potential mechanism of insulin action on glucose transport in the isolated rat diaphragm. Apparent translocation of intracellular transport units to the plasma membrane.

[3H]Cytochalasin B binding and its competitive inhibition by D-glucose have been used to quantitate the number of functional glucose transport units in plasma and microsomal membranes prepared from intact rat diaphragm. In a series of three experiments, plasma membranes prepared from diaphragms which have not been incubated with insulin bind approximately 16 pmol of cytochalasin B/mg of membrane protein to the D-glucose-inhibitable binding site. If 280 nM (40,000 microunits/ml) insulin is present during the incubation, cytochalasin B binding to the plasma membranes is increased approximately 2-fold without alteration in the dissociation constant of this site. Membranes in the microsomal fraction prepared from diaphragms which have been incubated for 30 min in the absence of insulin contain 21 pmol of D-glucose-inhibitable cytochalasin B binding sites/mg of membrane protein. However, in the presence of insulin during the incubation period, the number of these sites in the microsomal fraction is decreased to 12 pmol/mg of membrane protein. These results suggest that insulin stimulates glucose transport in the isolated rat diaphragm primarily through a translocation of functional glucose transport units from an intracellular membrane pool to the plasma membrane. These results are similar to the results observed in rat adipose cells (Cushman, S. W., and Wardzala, L. J. (1980) J. Biol. Chem. 255, 4758-4762) and suggest that this mechanism of insulin-stimulated glucose transport activity may be general to other cell types.

Adenylyl Cyclases↗
PubMed1981

Role of microtubules in insulin and glucagon stimulation of amino acid transport in isolated rat hepatocytes.

The effects of the microtubule inhibitor, colchicine, on insulin or glucagon stimulation of alpha-amino[1-14C]-isobutyric acid (AIB) transport were investigated in isolated hepatocytes from normal fed rats. Under all conditions tested, AIB uptake appeared to occur through two components of transport: a low affinity (Km approximately 50 mM) component and a high affinity (Km approximately 1 mM) component. Within 2 h of incubation, insulin and glucagon, at maximal concentrations, increase AIB (0.1 mM) uptake by 2- to 3-fold and 4- to 6-fold, respectively. Colchicine, at the low concentration of 5 X 10(-7) M, slightly reduces basal AIB transport, decreases by 80% the simulatory effect of insulin, and diminishes by 40% the stimulatory effect of either glucagon or dibutyryl cAMP. Kinetic analysis of AIB influx indicates that the drug inhibits the increase in Vmax of a high affinity (Km approximately 1 mM) component of transport stimulated by insulin or glucagon, without affecting the kinetic parameters of a low affinity component of transport (Km approximately 50 mM). Various short term hormonal effects of insulin and glucagon (changes in glucose, urea, and lactate production) were found not to be modified by the drug. Vinblastine elicits similar changes as colchicine on AIB uptake. Lumicolchicine, a colchicine analogue that does not bind to tubulin, has no effect. The concentration of colchicine (10(-7) M) required for half-maximal inhibition of hormone-stimulated AIB transport is in the appropriate range for specific microtubule disruption. These data suggest that microtubules are involved in the regulation of the insulin or glucagon stimulation of AIB transport in isolated rat hepatocytes.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1981

Possible involvement of the cholinergic system in hormonal secretion by the perfused pancreas from ventromedial-hypothalamic lesioned rats.

Total arginine-induced secretion of insulin, glucagon and somatostatin was studied during a 20 min period in isolated perfused pancreases from control and non-hyperphagic ventromedial hypothalamic (VMH) lesioned rats. Compared to controls pancreases from VMH-lesioned rats secreted more insulin (82 +/- 13 ng vs 36 +/- 9 ng) and more glucagon (130 +/- 23 ng vs 73 +/- 14 ng) but less somatostatin (0.58 +/- 0.18 ng vs 1.12 +/- 0.14 ng). These abnormalities were restored to normal by perfusion with atropine (25 mumol/l). Pancreases of both groups were perfused with the cholinergic agonist methacholine (100 mumol/l). Again pancreases from VMH-lesioned rats secreted more insulin (157 +/- 19 ng vs 33 +/- 6 ng) and more glucagon (95 +/- 13 ng vs 57 +/- 9 ng) but less somatostatin (0.80 +/- 0.15 ng vs 1.30 +/- 0.18 ng). These results support the concept that, in pancreases isolated from VMH-lesioned rats increased "cholinergic activity" may prevail via increased release of endogenous acetylcholine from islet-postsynaptic ganglion cells together with increased numbers of muscarinic receptors on postsynaptic ganglion cells as well as on endocrine cells.

Animals↗
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

Chorda tympani and vagus nerve convergence onto caudal brain stem neurons in the rat.

Neurons responsive to chorda tympani (CT) and cervical vagus (CV) nerve stimulation were identified electrophysiologically in the caudal brain stem of the anesthetized rat. All identified dually responsive (CT/CV) neurons included in this study were orthodromically activated by both CT and CV stimulation (n = 80). These cells were located mainly in the lateral nucleus tractus solitarius (nts) or more ventrally in the region of nucleus ambiguus (amb). No CT/CV cells were found to lie clearly within the dorsal motor nucleus of the vagus nerve. Among CT/CV neurons in nts, there was no correlation of response latency to Ct stimulation versus response latency to CV stimulation, while CT/CV neurons found in the region of amb demonstrated a good correlation between the two stimuli and suggested that sensory convergence occurred prior to the level of amb. Conditioning pulses applied to CV were able to alter the neural response of characteristics to CT test pulses in a majority of the units tested. It is concluded that oropharyngeal afferents converge on brain stem neurons that are also responsive to vagal afferent input. These dually responsive CT/CV neurons are implicated in the integration of sensory information relevant for cephalic phase reflexes.

Animals↗
PubMed1981

Nucleus ambiguus stimulation increases plasma insulin levels in the rat.

The ventral lateral brainstem has been explored for sites that facilitate insulin release unilaterally, using electrical stimulation techniques in male rats anesthetized with alpha-chloralose/urethane. Stimulation in the region of nucleus ambiguus (amb) produced a rapid rise (by 1 min) in plasma insulin levels, whereas stimulation of brainstem regions further than 500 micrometers from amb had no consistent effect on insulin levels. The amb-induced rise in insulin was markedly exaggerated by the alpha-adrenergic antagonist, phentolamine, and was greatly diminished by bilateral cervical vagotomy or atropine pretreatment. These results strongly suggest that the amb is one source of vagal motoneurons that facilitate insulin secretion. However, amb electrical stimulation alone also activated an apparent sympathetic efferent output whose inhibitory effect on insulin release could be blocked by phentolamine.

Animals↗
PubMed1981

Importance of cholinergic innervation of the pancreas for glucose tolerance in the rat.

Because cholinergic innervation of the pancreas is of importance in control of oral glucose tolerance, it seems important to determine whether transplanted pancreatic tissue becomes reinnervated with cholinergic fibers. Oral and intravenous glucose tolerance tests (ivGTT) were performed with and without atropine treatment on streptozotocin-diabetic rats treated by intraportal transplantation of isogenic islets 13-15 wk previously and on sham-operated nondiabetic controls. Atropine had no effect on the ivGTT of transplanted rats or controls. In controls atropine caused a deterioration of the oral glucose tolerance, abolished the preabsorptive insulin release, and also diminished the early part of the glucose-induced insulin release in these animals. In the absence of atropine, transplanted rats had pathological oral glucose tolerance, preabsorptive insulin release was absent, and glucose-induced insulin release was diminished compared to controls. Atropine had little effect on the oral GTT of transplanted rats. The present results underline the importance of the vagus nerve in the control of oral glucose tolerance and show that the vagus nerve in rats, at least under these experimental conditions, does not modulate the insulin response to intravenous glucose. The results suggest that intraportally transplanted islets remain functionally vagotomized.

Animals↗
PubMed1981

Abnormal water turnover associated with hypothalamic obesity.

Experimental obesity produced in rats by stereotaxic lesions of the ventromedial hypothalamus (VMH) resulted in hyperphagia, polydipsia, polyuria, decreased urine osmolality, and enhanced excretion of total solute and urea. A 24-h water deprivation test revealed the inability of VMH-lesioned rats to increase urine antidiuretic hormone (ADH) excretion. Thus, destruction of the VMH area appears to be accompanied by impairment of ADH secretion, resulting in a diabetes insipidus syndrome that is partially masked by food restriction and improved by treatment with exogenous ADH.

Animals↗
PubMed1981

Cephalic phase, reflex insulin secretion. Neuroanatomical and physiological characterization.

Using chronically catheterized, freely moving male Wistar rats, we have shown that the sweet taste of a saccharin solution reliably triggers a rapid cephalic phase insulin response (CPIR), in the absence of any significant change of glycemia. To establish the neural mediation of this reflex response we used rats that were cured from streptozotocin diabetes by intrahepatic islet-transplantation as a denervated B-cell preparation. The complete lack of any saccharin-induced CPIR in these rats suggests that it is indeed mediated by the peripheral autonomic nervous system, and that the insulin-stimulating gastrointestinal hormones are not involved in this response. It was further found that this reflex insulin secretion is not easily extinguishable and thus might have an unconditioned component. To investigate the central neural pathways involved in this reflex response we used both electrophysiological methods in anesthetized and semi-micro CNS manipulations in freely moving rats. On the basis of our preliminary results, and several reports, using the decerebrate rat preparation for measuring behavioral or saliva secretory oral taste reactivity, it appears that the CPIR might be organized at the brain stem/midbrain level, receiving strong modulatory influences from the diencephalon. But much further work has to be done to establish the central nervous circuitry. Finally, in two experiments, aiming at the question of how important and physiologically relevant the CPIR might be, we found that, on one hand, its lack can result in pathological oral glucose tolerance and on the other hand its exaggeration might contribute to the behavioral reaction to highly palatable sweet food and the resulting development of dietary obesity.

Animals↗
PubMed1981

CNS modulation of pancreatic endocrine function. Multiple modes of expression.

The involvement of the CNS in pancreatic hormone release has been studied. 1.) It has been shown that one source of vagal efferent fibers capable of facilitating insulin secretion originated in the rostral half of the nucleus ambiguus. 2.) Acute lesions of the ventromedial hypothalamus resulted in hyperinsulinaemia that could be abolished by acute vagotomy. 3.) Chronic lesions of the ventromedial hypothalamus increased secretion of insulin and glucagon, and decreased secretion of somatostatin when the pancreas was subsequently isolated and perfused. These changes were attributed to altered cholinergic activity related to previous ventromedial hypothalamic lesions as they could be reversed toward normal by atropine infusion or mimicked by the cholinergic agonist, methacholine. 4.) Electrical stimulation of the lateral hypothalamus in anaesthetized rats produced both an inhibitory component of insulin secretion, probably related to adrenergic stimulation, and a stimulatory component, probably due to the release into the blood of factor(s) that promote insulin secretion. 5.) The anatomical organization of brain of the genetically obese (ob/ob) mice is abnormal. These abnormalities could be involved in the endocrinological disturbances of these animals.

Animals↗
PubMed1980

Altered dendritic orientation of hypothalamic neurons from genetically obese (ob/ob) mice.

Individual Golgi-stained neurons from the ventromedial nucleus (VMN) and lateral hypothalamic area (LHA) were analyzed from genetically obese and lean mice. No strain differences were noted for the number of dendrites or the position of dendritic branch points as a function of distance from the cell body for any of the hypothalamic areas sampled. However, both LHA and VMN neurons showed altered dendritic orientation between mouse strains.

Animals↗
PubMed1980

Insulin resistance in soleus muscle from obese Zucker rats. Involvement of several defective sites.

1. The effect of insulin upon glucose transport and metabolism in soleus muscles of genetically obese (fa/fa) and heterozygote lean Zucker rats was investigated at 5-6 weeks and 10-11 weeks of age. Weight-standardized strips of soleus muscles were used rather than the intact muscle in order to circumvent problems of diffusion of substrates. 2. In younger obese rats (5-6 weeks), plasma concentrations of immunoreactive insulin were twice those of controls, whereas their circulating triacylglycerol concentrations were normal. Insulin effects upon 2-deoxyglucose uptake and glucose metabolism by soleus muscles of these rats were characterized by both a decreased sensitivity and a decrease in the maximal response of this tissue to the hormone. 3. In older obese rats (10-11 weeks), circulating concentrations of insulin and triacylglycerols were both abnormally elevated. A decrease of 25-35% in insulin-binding capacity to muscles of obese rats was observed. The soleus muscles from the older obese animals also displayed decreased sensitivity and maximal response to insulin. However, at a low insulin concentration (0.1m-i.u./ml), 2-deoxyglucose uptake by muscles of older obese rats was stimulated, but such a concentration was ineffective in stimulating glucose incorporation into glycogen, and glucose metabolism by glycolysis. 4. Endogenous lipid utilization by muscle was calculated from the measurements of O(2) consumption, and glucose oxidation to CO(2). The rate of utilization of fatty acids was normal in muscles of younger obese animals, but increased in those of the older obese rats. Increased basal concentrations of citrate, glucose 6-phosphate and glycogen were found in muscles of older obese rats and may reflect intracellular inhibition of glucose metabolism as a result of increased lipid utilization. 5. Thus several abnormalities are responsible for insulin resistance of muscles from obese Zucker rats among which we have observed decreased insulin binding, decreased glucose transport and increased utilization of endogenous fatty acid which could inhibit glucose utilization.

Animals↗