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Biomedical subjects

B Jeanrenaud

Publications and source records attributed to B Jeanrenaud.

At least 181 records · Page 10Linked to original sources
PubMed1980

A possible complementary role of actin microfilaments and microtubules in triacylglycerol secretion by isolated rat hepatocytes.

Incubation of isolated rat hepatocytes with phalloidin, cytochalasins (which, respectively, stabilize and destabilize actin microfilaments), or colchicine (which inhibits polymerization of microtubules), resulted in a dose-dependent inhibition of triacylglycerol secretion (an index of very low density lipoprotein secretion). Upon removal of drugs from incubation media, the inhibitory effect of cytochalasin D on triacylglycerol secretion was reversible, while such was not the case of phalloidin. When used at maximal concentrations, the combined presence of phalloidin + colchicine or cytochalasin D + colchicine had additive inhibitory effects upon hepatic triacylglycerol secretion, which was virtually blocked; this was not the case for phalloidin + cytochalasin D. These experiments support the concept that microfilaments and microtubules may have complementary functions for the hepatic secretion of very low density lipoproteins.

Actins↗
PubMed1980

Hypothalamic input to brain stem neurons responsive to oropharyngeal stimulation.

The aim of this study was to determine if electrical stimulation of diencephalic sites previously implicated in feeding behavior and metabolic homeostasis could influence the unit activity of caudal brain stem neurons receiving oropharyngeal input. Electrical stimulation of the chorda tympani nerve (CT) was used to first identify brain stem units. A significant number of these CT-responsive neurons could also be driven by lateral hypothalamic area (LHA) stimulation. Medially placed diencephalic stimulating electrodes were not effective in altering unit activity of CT-responsive brain stem neurons. Tests of temporal summation showed that LHA conditioning pulses could significantly alter brain stem unit responses to CT test pulses at short interpulse intervals. These results demonstrate the presence of descending input from the LHA-medial forebrain bundle (MFB) to brain stem neurons possibly involved in oropharyngeal sensation and gustatory-evoked phenomena.

Afferent Pathways↗
PubMed1980

Role of the autonomic nervous system in the mediation of LHA electrical stimulation-induced effects on insulinemia and glycemia.

The short-term effects of bilateral electrical stimulation of the lateral component of the lateral hypothalamic/medial forebrain bundle area (LHA) on peripheral plasma levels of glucose (G), immunoreactive insulin (IRI) and glucagon (IRG) were measured in food-derived, anesthetized rats in the presence of continuous low i.v. glucose infusion. In normal rats LHA stimulation induced a rapid but moderate rise in IRI in the presence of a simultaneous rapid rise in G. At the end of the 5 min stimulation period the glucose-induced IRI response was clearly attenuated. In rats receiving a continuous phentolamine (i.v.) infusion, the rapid IRI response was much larger in spite of only marginal rises of G. These findings suggest that electrical LHA stimulation activates two opposing mechanisms on IRI secretion, an excitatory component which is masked in normal animal by a sympathetic alpha-adrenergic inhibitory component. In an attempt to define the mediating pathway of this LHA stimulation-induced IRI excitatory component, both the parasympathetic and sympathetic divisions of the autonomic nervous system were pharmacologically and surgically manipulated, all in the presence of phentolamine infusion. Neither bilateral subdiaphragmatic vagotomy, atropine, propranolol infusion, nor spinal cord transection at T1 were able to block the IRI response. The findings are consistent with a humoral mediation of this IRI stimulatory response and support the existence of a lateral hypothalamic or hypophyseal factor which is released by LHA stimulation. The implications and physiological role of the LHA in the neural control of insulin secretion and ingestive behavior are discussed.

Animals↗
PubMed1980

Nitrogen handling in adult hypothalamic obese rats.

Several aspects of nitrogen metabolism have been studied in adult nonhyperphagic, hyperinsulinemic, ventromedial hypothalamus (VMH)-lesioned rats. Ten days postoperatively, VMH-lesioned rats had high plasma levels of urea and low plasma tyrosine, while plasma alanine, glutamine, total amino acid, and protein levels were unaltered. Urea production and excretion were increased in VMH-lesioned rats. Increased urea synthesis could not be attributed to enhanced peripheral release of amino acids. In vitro, measurements of hepatic amino acid uptake and liver protein synthesis did not reveal any disturbances of these processes in VMH-lesioned rats. However, hepatic transamination and lipogenesis from amino acids were increased following VMH-lesions. In addition to the hyperinsulinemia previously reported to occur in nonhyperphagic VMH-lesioned rats, this study showed an increased glucagon secretion from perfused pancreases of these animals. These data together suggest that the excess of the two hormones at the portal vein of VMH-lesioned rats would favor uptake and deamination of amino acids, their diversion to lipid synthesis and possibly other pathways, with consequent increase in urea production and reduced supply of amino acids to peripheral tissues available for nitrogen retention.

Amino Acids↗
PubMed1980

Cephalic-phase insulin secretion in normal and pancreatic islet-transplanted rats.

The ability of saccharin, in comparison with glucose and tap water, to elicit glycemia-independent neurally mediated insulin secretion was investigated in chronically catheterized, freely moving rats. Plasma glucose and insulin concentrations were measured continuously from venous blood with a sampling resolution of one per minute. In normal rats, 1 ml of 0.15% saccharin caused a significant rapid rise in peripheral plasma insulin levels lasting up to 5 min, without significant changes in glycemia. Tap water alone also induced a transient elevation in insulinemia but was much smaller than the saccharin-induced response. In streptozotocin diabetic rats bearing intrahepatic, presumably denervated islet isografts, these rapid insulin responses to oral saccharin and tap water stimulation were completely abolished, whereas the early insulin response to intravenous glucose was decreased by only about 30%. These results are consistent with the concept of gustatory and other oral sensory signals acting as triggers for neurally mediated insulin release.

Animals↗
PubMed1980

Consequences of ventromedial hypothalamic lesions upon insulin and glucagon secretion by subsequently isolated perfused pancreases in the rat.

The existence of a relationship between the ventromedial hypothalamic area (VMH) and the activity of the endocrine pancreas has been shown previously. This relationship has been further tested and extended in the present study, using isolated perfused pancreases from rats previously lesioned (4-7 d) in the VMH. It was found that in isolated pancreases obtained from rats fed ad lib. for 4 d after VMH lesions (i.e., that were hyperphagic), the typical biphasic pattern of insulin secretion was observed following glucose stimulation (20 mM) and that the total insulin output was much greater than that of controls. The increased insulin output was not a result of hyperphagia because similar results were obtained using pancreases obtained from VMH-lesioned rats in which a food restriction matching exactly that of control rats was started either immediately of 3 d after the lesions. Pancreases from such food-restricted VMH-lesioned rats oversecreted insulin, when compared with controls fed the same amount, from 7 mM of glucose concentration in perfusion medium onwards. After the addition of arginine (10 mM), the total output of glucagon by pancreases from food-restricted VMH-lesioned rats was twice that of controls. Qualitatively, the arginine-induced glucagon secretion by pancreases from food-restricted VMH-lesioned rats retained its biphasic pattern. Similarly, epinephrine (0.1 muM) elicited a greater glucagon release by pancreases from food-restricted VMH-lesioned rats when compared with controls. These data further support the concept of a link (as yet undefined) between the hypothalamus and the endocrine pancreas, as lesions of the VMH area resulted in abnormal secretion not only of insulin, but of glucagon as well.

Animals↗
PubMed1979

Altered neuroanatomical organization in the central nervous system of the genetically obese (ob/ob) mouse.

Genetically obese (C57BL/6J ob/ob) mice have significantly reduced brain weights (-14.6%) and cortical brain volumes (-7.9%) compared to lean control mice (C57BL/6J +/+). Morphometric analyses of soma cross-sectional areas of individual neurons in select brain region also reveals significant alterations in the ob/ob mouse. Neurons from 8 out of 9 brain regions, including the ventromedial hypothalamic nucleus, show significantly decreased soma cross-sectional areas in ob/ob mice compared to controls. Only lateral hypothalamic area neurons have equivalent soma cross-sectional areas for these two mouse strains. The decreased brain weight and volume coupled with the observed morphometric changes in individual neuronal soma size suggest that the ob/ob mouse brain differs considerably from that of controls. These differences may underlie some of the endocrine abnormalities seen in this genetic obesity syndrome.

Animals↗
PubMed1979

Actin microfilaments, cell shape, and secretory processes in isolated rat hepatocytes. Effect of phalloidin and cytochalasin D.

The effects of phalloidin and cytochalasin D, drugs which, respectively, stabilize and destabilize actin microfilaments, have been tested on isolated rat hepatocytes. Both drugs produced a modification of cell shape, characterized by protrusions bulging from the cytoplasm. In phalloidin-treated hepatocytes, an accumulation of actin microfilamentous network was detectable at the base of each protrusion by electron microscopy, immunofluorescence, and HMM decoration. This accumulation of microfilaments was absent in cytochalasin D-treated cells. The release of triglycerides, an index of very low density lipoprotein secretion, was inhibited by phalloidin or cytochalasin D, and accompanied by an increase in cellular triglycerides. At the electron microscope examination, triglyceride accumulation was represented by fat droplets and vesicle-enclosed, very low density lipoprotein-like particles. Total protein and albumin secretion was only very slightly modified by either one of these drugs. With the use of various phalloidin analogs, a correlation was observed between their respective ability to stabilize F-actin in vitro, and their effects on cell shape and triglyceride secretion. In conclusion, phalloidin, and cytochalasin D: (a) modify the shape of isolated hepatocytes; (b) inhibit lipoprotein secretion. These effects possibly result from a modification of actin microfilament function.

Actins↗
PubMed1979

alpha-Sympathetic control of glucose output of mouse liver perfused in situ.

Electrical stimulation of perivascular nerve bundles of mouse liver perfused in situ at constant flow resulted in an increase of glucose production that was maximal at 20 Hz. The neurally induced glucose output was inhibited significantly by the beta-blocker propranolol, and to a considerably greater extent by the alpha-blockers, phenoxybenzamine and phentolamine. The effect of 20-Hz electrical stimulation could be matched by an infusion of norepinephrine at a concentration of 5 X 10(-7) M. It is suggested that the carbohydrate metabolism of the liver is controlled by its own nerve supply rather than by circulating catecholamines and that alpha-adrenergic receptors have a greater effect than beta-receptors on hepatic glucose production resulting from electrical and catecholamine stimulation.

Animals↗
PubMed1979

Identical biological effects of pancreatic glucagon and a purified moiety of canine gastric immunoreactive glucagon.

Because in the dog, the gastric fundus contains the largest amount of glucagon immunoreactivity (IRG), the IRG of mucosal scrapes of 105 canine stomachs was extracted by acid-ethanol and then precipitated by ether-ethanol. The IRG recovered was measured by antisera 30K, specific for glucagon and K-4023, which cross-reacts with glucagon-like immunoreactivity. Extracts of mucosa of stomach fundus were further purified by gel filtration on Bio-Gel P-30 in 3M acetic acid. One pooled fraction corresponding to marker pancreatic glucagon in its elution volume was then gel-filtered on Bio-Gel P-30 in 0.05 M NH(4)HCO(3) and yielded one IRG peak, which, however, showed three immunoreactive components on polyacrylamide disc gel electrophoresis in urea. In addition, antiserum K-4023 reacted more strongly with that peak than antiserum 30K indicating the presence of glucagon-like immunoreactivity in this fraction. Subsequent ion-exchange column chromatography on DEAE-Sephadex A-25 and then CM-Bio-Gel A allowed purification to a single protein band on disc gel electrophoresis reacting equally to both antisera 30K and K-4023. 1.5 mug of purified gastric glucagon was obtained and its biological effects were compared to those of pancreatic glucagon in isolated rat hepatocytes. When immuno-equivalent amounts (300-2,500 pg/ml) of either type of glucagon were used, the same biological responses with respect to glycogenolysis and gluconeogenesis as well as urea, lactate, and pyruvate production were observed. Liver cyclic AMP was also raised to the same extent by either one of these hormones. We conclude that this moiety of gastric IRG is apparently identical to pancreatic glucagon because (a) their molecular weights, elution properties in ion exchange chromatography, and their electrophoretic mobility are indistinguishable and (b) both hormones elicited identical biological effects in isolated rat hepatocytes.

Animals↗
PubMed1979

Acute hyperinsulinemia and its reversal by vagotomy after lesions of the ventromedial hypothalamus in anesthetized rats.

The acute effect of bilateral electrolytic ventromedial hypothalamic lesions (20-25-m Coulomb stainless steel electrodes) on plasma levels of insulin and glucose was studied in anesthetized rats to determine early effects that would occur before hyperphagia and obesity. In rats fed ad libitum, lesions in the ventromedial hypothalamus (VMH) but not in the cortex produced a marked increase in circulating insulin levels (starting at 20 min postlesion) and a small increase in glycemia which, however, was not significant and could therefore not be the cause of increased insulin secretion. Hyperinsulinemia after VMH lesions was more pronounced when glucose was infused iv at a rate of 7-8 mg/kg . min. Bilateral subdiaphragmatic vagotomy, performed 50 min after VMH lesions, immediately and completely reversed the observed hyperinsulinemia. With the exception of a tendency of lesions producing the highest degree of hyperinsulinemia to be slightly larger than the lesions not producing any hyperinsulinemia, no statement about the critical involvement of a specific hypothalamic locus can be made. It is concluded that electrolytic VMH destruction causes immediate hypersecretion of the pancreatic B cell, an effect that requires the integrity of the vagus nerves. Further localization of the central circuitry responsible for this mechanism, however, will require more specific methods than electrolytic lesions.

Animals↗
PubMed1979

Animal obesities.

Genetically or experimentally-produced (e.g. via lesions of the hypothalamus) obese animals have several common features such as increased hepatic lipogenesis (resulting in fat infiltration) and increased hepatic lipoprotein secretion, together, with increased adipose tissue lipogenesis. These abnormalities appear to be related primarily to hyperinsulinemia as they are reversed to or toward normal when hyperinsulinemia is corrected or, conversely, as they develop concomitantly with hyperinsulinemia. In the liver (ob/ob mice), another defect can be demonstrated, i.e. a decreased hepatic insulin clearance. This defect is also related to hyperinsulinemia and is markedly reduced upon normalizing hyperinsulinemia of obese mice. Hyperinsulinemia may thus be a key feature of the obesity syndromes, and bring about most of the abnormalities noted, including the subsequent state of insulin resistance known to exist in obese animals. The etiology of hyperinsulinemia of genetically obese animals is still unknown. Among the possible mechanisms one should cite possible primary dysfunction of the pancreas, possible primary dysregulation, by the hypothalamus, of overall endocrine pancreas activity.

Adipose Tissue↗
PubMed1979

Glucose production by the perfused liver of the spiny mouse (Acomys cahirinus): sensitivity to glucagon and insulin.

Hepatic glucose production and its responses to glucagon and insulin were studied in perfused livers obtained from spiny mice (Acomys cahirinus)--rodents characterized by normoglycemia, decreased glucose tolerance and decreased insulin secretion--and from Swiss albino mice. The dose-response characteristics of glucagon-induced hepatic glucose output were similar in spiny and albino mice. However, maximally stimulated glucose production were significantly lower in the spiny mouse. Furthermore, the liver of the spiny mouse was more sensitive to the action of insulin: 0.5 X 10(-6) M insulin significantly inhibited the action of glucagon in spiny mice but not in albino mice. It is proposed that the increased sensitivity of the hepatic glucose output to insulin and the decreased maximal stimulation by glucagon may be factors that limit the negative effects of the impaired insulin secretion in spiny mice, thereby reducing the severity of the glucose intolerance. Analogous mechanisms may be present in the early stages of the diabetic syndrome in man.

Animals↗
PubMed1978

Hyperinsulinemia in obesity syndromes: its metabolic consequences and possible etiology.

Animal models with genetic or experimentally produced (lesions of hypothalamus) obesities are numerous and unlikely to ever be reduced to a single pathophysiologic entity. However, obese animals have many similar traits in common. They are all hyperinsulinemic, an abnormality that occurs early in the development of these syndromes and appears to be of prime importance in producing most of the metabolic changes observed both in the early and late phases of the obesity syndromes. In all instances, obesity is an evolutional syndrome in which the early phase is different from the later one. The early phase is principally characterized by increased hepatic very low density lipoprotein (VLDL) output, increased adipose tissue lipogenesis and VLDL uptake, hence, increased fat accretion and fat cell size. These abnormalities are secondary to hyperinsulinemia and can be reversed toward normal by normalizing circulating insulin levels. The late phase is characterized by the continuation of the disorders of the early one plus a superimposed abnormality, the insulin resistance state, that is detectable particularly at the level of adipose and muscle tissues, and eventually brings about hyperglycemia. Insulin resistance is a multifactorial pathological condition that includes at least: (a) a decrease (more or less marked) in insulin binding to target tissues that is responsible for the decrease in tissue sensitivity to the hormone; (b) intracellular defects that are probably responsible for the decreased insulin responsiveness of target tissues. The origin of hyperinsulinemia in animal obesities is still ill-defined. Lesions of the ventromedial hypothalamus (VMH) produce rapid and lasting hyperinsulinemia. Such lesions produce, in addition, increased secretion of insulin and glucagon and changes in pancreatic insulin, glucagon, and somatostatin content in subsequently perfused pancreases. The locus responsible for these effects is not defined and may actually involve a series of interrelated loci. Whatever the latter may be, one of the routes of CNS influence upon endocrine pancreas is the vagus nerve, although a humoral factor has also been claimed. The etiology of hyperinsulinemia in genetically obese animals is unknown. Genetic inheritance could bear primarily upon some hypothalamic or other CNS sites, with secondary alterations in the endocrine pancreas function, or primarily on the islets of Langerhans with possible alteration in the respective function of the A, B, and D cells with resulting excessive insulin secretion.

Animals↗
PubMed1978

Insulin binding and effects in isolated soleus muscle of lean and obese mice.

To get some insight into the mechanisms of insulin resistance in obesity, insulin binding and biological effects were investigated in soleus muscles isolated from normal and obese mice. Basal and insulin-stimulated 2-deoxyglucose uptake were measured at the steady state of insulin binding. The results were consistent with the concept of spare receptors, i.e., maximal insulin effect was achieved when only about 20% of total receptors was occupied. When similar studies were applied to muscles of gold thioglucose obese or genetically obese (ob/ob) mice, and compared to lean controls: a) insulin binding was decreased; b) the insulin dose-response curve of 2-deoxyglucose uptake was shifted to the right; c) maximally insulin-stimulated 2-deoxyglucose uptake, glycolysis, and glycogen synthesis were markedly decreased. Insulin binding and effects returned toward normal after a 40-h fast in obese mice. These results point to two loci for the insulin resistance of skeletal muscle in obesity: 1) a decrease in the number of insulin receptors, which results in a diminished insulin sensitivity; and 2) one or more alterations beyond receptor that are responsible for the decreased responsiveness of the tissue to insulin and appear to play a major role in the insulin resistance of muscle in obesity.

Animals↗