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Biomedical subjects

B Jeanrenaud

Publications and source records attributed to B Jeanrenaud.

At least 145 records · Page 8Linked to original sources
PubMed1983

Evidence for a role of the gastric, coeliac and hepatic branches in vagally stimulated insulin secretion in the rat.

Either the left or right cervical vagus was electrically stimulated in anesthetized rats before and after selective transection of either the coeliac, gastric and hepatic abdominal branches in order to evaluate the contribution of these branches to vagal controlled insulin secretion. Changes of insulin secretion were estimated on the basis of insulin concentration in venous plasma, sampled by indwelling jugular catheters. Plasma glucose concentration in overnight food-deprived rats was clamped between 130 and 160 mg/dl by means of continuous i.v. glucose infusion, and surgical stress-induced sympathetic activity was blocked by concomitant i.v. infusion of phentolamine and propranolol. Before transection of any abdominal branch, both right and left cervical vagal stimulation induced a 3- to 4-fold increase of plasma insulin concentration and significant increases of plasma glucose concentration, while the heart rate decreased rapidly and significantly. The right cervical vagal stimulation-induced insulin response (integrated incremental area) was significantly decreased by either bilateral coeliac (-37%) or bilateral gastric (-57%), but not by hepatic (-5%) vagotomy. The left cervical vagal stimulation-induced insulin response was significantly decreased (-41%) by hepatic vagotomy. The concomitant rises of plasma glucose concentration may have contributed more than 50% to the vagal stimulation-induced insulin responses. However, calculating the purely neural components revealed that the right cervical vagal stimulation-induced insulin response was still decreased by coeliac (-48%) or gastric (-84%) and not decreased (+24%) by hepatic vagotomy, and the left cervical vagal stimulation-induced insulin response was decreased (-52%) by hepatic branch vagotomy. We conclude that cervical vagal stimulation-induced insulin-secreting activity reaches the pancreas via all 3 abdominal divisions of the vagus nerve, and suggest that pancreatic beta-cells are innervated through all 3 abdominal divisions.

Animals↗
PubMed1983

The origins and role of efferent vagal nuclei in hyperinsulinemia in hypothalamic and genetically obese rodents.

The main brainstem parasympathetic efferent neurons that ultimately reach the pancreas and facilitate insulin secretion are located in the nucleus ambiguus (NA) and the dorsal motor nucleus of the vagus nerve (DMX). With regard to insulin secretion, hypothalamic (produced by ventromedial hypothalamic (VMH) lesions) and genetic obesities have features in common: (a) insulin oversecretion is an early abnormality in both syndromes; and (b) this abnormality is vagus nerve-mediated. VMH lesions and possible, spontaneously occurring (i.e. genetic) CNS-located abnormalities appear to result in an increased parasympathetic efferent tone together with decreased sympathetic efferent tone that is likely to be responsible for the occurrence of hyperinsulinemia, obesity and, eventually, insulin resistance.

Animals↗
PubMed1983

Vagal neurons and pathways to the rat's lower viscera: an electrophysiological study.

The vagal pathways to the rat's pancreas are anatomically difficult to describe. A stimulation/recording technique has been used on various segments of the vagus to trace vagal pathways to the lower viscera, and a microelectrode recording technique to locate vagal neurons of origin in the brain stem's dorsal motor nucleus (DMX). The two main pathways (right cervical vagus to dorsal celiac branch and left cervical vagus to ventral celiac branch) are supplemented by two accessory ones where each cervical vagus gives some fibers to its contralateral homologue at the diaphragmatic level. These pathways consist almost exclusively of C-fibers. Neurons of origin of the dorsal vagal trunk fibers have been identified by the collision test and occupy the caudal half of the DMX; those of the dorsal celiac branch fibers originate from the medial part of that area.

Abdomen↗
PubMed1983

Hyperinsulinemia of preobese and obese fa/fa rats is partly vagus nerve mediated.

In vivo glucose-induced insulin secretion was greater in preweaned preobese 17-day-old Zucker rats than in the corresponding controls. This hypersecretion of insulin was reversed to normal by acute pretreatment with atropine. A short-lived (30 s) electrical stimulation of the vagus nerve preceding a glucose load potentiated the in vivo glucose-induced insulin release in adult animals (6-9 wk) and more so in obese Zucker (fa/fa) than in lean rats. This suggested the existence of enhanced sensitivity and/or responsiveness of the B cells of obese animals to the parasympathetic system. That the parasympathetic tone was increased in adult obese Zucker (fa/fa) rats was corroborated by the observation that acute vagotomy of these animals resulted in a significant decrease in glucose-induced insulin secretion, whereas no such effect was seen in lean rats. Also, perfused pancreases from adult obese (fa/fa) rats oversecreted insulin during a stimulation by arginine when compared with controls, an oversecretion that was restored toward normal by superimposed infusion of atropine. It is concluded that a) the increased insulin secretion of preobese Zucker fa/fa rats is an early abnormality that is mediated by the vagus nerve, and b) increased secretion of insulin in adult obese fa/fa rats continues to be partly vagus-nerve mediated, although a decreased sympathetic tone and other unknown defects could conceivably play a role as well.

Animals↗
PubMed1983

Increases in plasma insulin levels in response to electrical stimulation of the dorsal motor nucleus of the vagus nerve.

In order to investigate the physiological counterpart of the anatomical finding showing that the dorsal motor nucleus of the vagus nerve (DMX) is a source of efferent vagal fibers innervating the pancreas, unilateral electrical stimulation using monopolar electrodes (50 microA, 30 Hz, 0.2 msec) at a glycemia of 150 mg/100 ml was performed in normal anesthetized rats. DMX stimulation resulted in rapid (within 1 min) rise in plasma insulin levels (greater than or equal to 200%). Stimulation of the nucleus of tractus solitarius, anatomically connected to DMX, also produced a 50% increase in insulinemia. The effect of DMX stimulation was almost completely abolished by atropine pretreatment or acute bilateral subdiaphragmatic vagotomy. The effect of DMX stimulation was not potentiated by the alpha-adrenergic blocker (infusion of phentolamine) indicating that no inhibitory fiber was recruited during DMX stimulation. It is concluded that DMX is connected to the endocrine pancreas exclusively via vagal fibers and has a role in neurally mediated insulin release.

Animals↗
PubMed1983

In vivo hepatic and peripheral insulin resistance in genetically obese (fa/fa) rats.

The techniques of hyperglycemic and euglycemic clamps previously used in human investigation have been adapted to small rodents to measure in vivo peripheral (muscle, adipose tissues) glucose metabolism and in vivo hepatic glucose production, in lean and genetically obese (fa/fa) rats. The aim of the study was 1) to assess the in vivo relevance of previously described in vitro abnormalities of muscle and adipose tissues producing insulin resistance in genetically obese (fa/fa) rats; 2) to decide whether livers of obese rats were insulin resistant. It was observed that during either hyperglycemic or euglycemic clamps, peripheral glucose metabolism by muscle and adipose tissue of obese rats was similar to that of lean controls but at the cost, for the obese rats, of plasma insulin levels that were 3.5 times higher than control. This indicated that peripheral tissues of obese rats were indeed insulin resistant when tested in vivo. It was also observed that raising plasma insulin levels in lean rats inhibited the in vivo hepatic glucose production. In contrast, in obese rats, hepatic glucose production was high in spite of a marked increase in basal insulinemia. Furthermore, hepatic glucose production of obese rats failed to be inhibited by further increasing their hyperinsulinemia. This is the first demonstration of a hepatic insulin resistance in genetically obese fa/fa rats.

Animals↗
PubMed1983

A rat hypothalamic extract enhances insulin secretion in vitro.

Fractions from a partially purified ventrolateral hypothalamic (VLH) extract stimulate insulin (IRI) secretion when infused into isolated perfused rat pancreases. At a low glucose concentration (5 mM) in the perfusion medium, infusion of the VLH extract significantly increased insulin output when compared to controls infused with a cerebellar cortex extract. (IRI output with cerebellar cortex: 13.5 +/- 0.81; with VLH extracts: 40.9 +/- 9.4 ng/5 min, P less than 0.05). At a high glucose concentration (10 mM) in the perfusion medium, IRI secretion evoked by glucose was further augmented by the simultaneous infusion of the VLH extract (IRI output with glucose: 325.6 +/- 25.8; glucose + VLH extract: 448.1 +/- 33.0 ng/20 min, P less than 0.02). When pancreases were perfused with a solution containing 20 different amino acids [(AA) 6.6 mM final concentration] IRI secretion elicited by the AA was similarly augmented by the presence of the VLH extract (IRI output with AA: 101.8 +/- 14.9; AA + VLH extract: 179.8 +/- 21.9, P less than 0.02). However, IRI secretion as stimulated by arginine alone (3 mM) was not potentiated by the extract. It is suggested that the hypothalamic factor(s) responsible for this IRI secretion-promoting activity could contribute to the hypothalamic control of IRI secretion through a route which remains to be established.

Amino Acids↗
PubMed1983

Insulin binding and removal by livers of genetically obese rats.

Livers from 9-10-wk-old genetically obese and hyperinsulinemic (fa/fa) rats contained more DNA, proteins, and lipids than livers of age-matched controls. Actually, the increase in liver mass of fa/fa rats was mainly due to an increased cell number. On perfusion with insulin (1.75-16 nM), livers of obese fa/fa rats removed 35-40% less insulin per gram tissue than control livers. When calculated on a per organ basis, removal capacity was, however, similar in livers of control and obese fa/fa rats. The binding of 125I-insulin to as well as the insulin removal by isolated hepatocytes was also assessed. Contrary to previous unexpected data in which the downregulation of insulin receptors by hyperinsulinemia was reported not to prevail in hepatocytes from obese fa/fa rats, it was found that the binding capacity of hepatocytes from fa/fa rats was decreased by 45% without alteration of the binding affinity. Moreover, in hepatocytes from obese fa/fa rats, both binding and removal of insulin were lowered to an analogous extent. It is concluded that livers of obese fa/fa rats behave, with regard to insulin binding and removal, as those of other hyperinsulinemic obese animals.

Animals↗
PubMed1983

[The central nervous system-endocrine pancreas axis].

Some results suggesting the existence of gluco- and/or insulin-sensitive sites within the central nervous system (CNS) are recalled. In summary, it seems that when these sites are activated by the presence of glucose or insulin, there is an activation of the parasympathetic nervous system which is responsible for an increased peripheral insulin secretion and/or an hypoglycemia. This could possibly favour glucose disposal. Inversely, when the CNS lacks energy substrates, a cascade of events occurs which tend to increase peripheral glycemia. Bilateral lesions of the ventromedial hypothalamus (VMH) bring about a very early occurring hypersecretion of insulin which can be rapidly and completely abolished by vagotomy. It has also been shown that genetically pre-obese rats (fa/fa) do hypersecrete insulin in response to an i.v. glucose load. This suggests that hypersecretion of insulin of these animals could play a causative role in the development of their obesity. Moreover, this hypersecretion of insulin observed in genetic pre-obesity is abolished by acute atropine administration indicating the involvement of the parasympathetic nervous system in the development of their hyperinsulinemia and subsequent obesity. Cephalic phase insulin secretion seems to "optimalize" insulin secretion that occurs following a meal, as it appears to permit adequate glucose utilization and therefore glucose tolerance. Indeed, animals which are lacking cephalic phase insulin secretion do hypersecrete insulin while remaining hyperglycemic for a longer period of time when compared to animals which have a cephalic phase insulin secretion. Hypothalamic factors present in the ventromedial or the ventrolateral hypothalamus have been shown to have insulin secretion promoting activity when administered in vivo or in vitro to donor rats. It remains to be shown whether such factors are indeed released into the blood (humoral factors) or whether they are neuromodulators and/or neurotransmitters.

Afferent Pathways↗
PubMed1982

Parallel increases in rates of fatty acid synthesis and in pyruvate dehydrogenase activity in isolated rat hepatocytes incubated with insulin.

The effect of insulin on the activity of pyruvate dehydrogenase is studied in isolated hepatocytes from fed rats. Insulin increases the 'initial' activity of pyruvate dehydrogenase by 30% without modifying the total activity of the enzyme. The maximal increase is reached 3 min after addition of the hormone and is dose-dependent. Insulin also increases the rate of fatty acid synthesis.

Aminoisobutyric Acids↗
PubMed1982

Sham feeding-induced cephalic phase insulin release in the rat.

The effect of the cephalic phase of food ingestion on plasma insulin and glucagon concentration was assessed in the sham-feeding rat, bearing chronically implanted gastric drainage fistulas. It was found that continuous sham feeding produced a significant and phasic peripheral insulin response in the absence of any significant changes of glycemia. The response was almost completely blocked by prior intravenous administration of 2 mg/kg of atropine methyl nitrate and potentiated by prior intravenous administration of 1.0 or 2.5 mg/kg of phentolamine. In spite of the larger insulin response after phentolamine, there was no hypoglycemia detected. Furthermore, continuous sham feeding did not produce a significant glucagon response, whereas real feeling did. The results demonstrate that cholinergic insulin release is triggered phasically by continuous ingestion of familiar food and that this insulin response is inhibited by an alpha-adrenergic sympathetic tone. It is further concluded that the increased glucose disposal produced by the neurally released insulin is not counteracted by a concomitant glucagon response or by direct adrenergic stimulation of hepatic glucose production.

Animals↗
PubMed1982

Physical training of lean and genetically obese Zucker rats: effect on fat cell metabolism.

The effects of 6-wk treadmill training program on the metabolism of isolated adipose cells from obese (fa/fa) and lean (Fa/?) Zucker rats were studied. Glucose metabolism and transport, insulin binding, and lipolysis were measured in adipose cells prepared from sedentary control and exercise-trained (ET) lean and/or obese rats. Two- to threefold increases in glucose metabolism were observed in cells from lean and obese ET rats compared with their respective controls. However, the insulin concentrations giving half-maximal stimulation (measuring insulin sensitivity) did not change (approximately 8 microunits/ml in lean and approximately 45 microunits/ml in obese rats). In lean ET rats, glucose transport and maximal glucose metabolic capacity (transport not rate-limiting) were increased twofold and sensitivity of lipolysis to epinephrine was increased three- to fourfold. These were not measured in obese rats. The results suggest that training of both lean and obese Zucker rats increases glucose utilization in adipose cells by increasing both glucose transport and intracellular glucose metabolism. Increased triglyceride turnover is also suggested by the increased sensitivity of lipolysis to epinephrine.

Adipose Tissue↗
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↗