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  • 1
    ISSN: 1432-0428
    Keywords: Ventromedial hypothalamus (VMH) ; isolated perfused pancreas ; insulin secretion ; glucagon secretion ; somatostatin secretion ; methacholine ; atropine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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±13ng vs 36±9ng) and more glucagon (130±23ng vs 73±14ng) but less somatostatin (0.58±0.18ng vs 1.12±0.14ng). These abnormalities were restored to normal by perfusion with atropine (25 μmol/l). Pancreases of both groups were perfused with the cholinergic agonist methacholine (100 μmol/l). Again pancreases from VMH-lesioned rats secreted more insulin (157±19ng vs 33±6ng) 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.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 20 (1981), S. 417-425 
    ISSN: 1432-0428
    Keywords: Acute ventromedial hypothalamic lesions (VMH) ; chronic VMH lesions ; lateral hypothalamus stimulation ; nucleus ambiguus stimulation ; insulin secretion ; glucagon secretion ; somatostatin secretion ; brain organization of obese (ob/ob) mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Obese fa/fa rat ; non-insulin-dependent diabetes ; oral glucose tolerance ; diabetic microangiopathy ; retinal capillary
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Genetically obese fatty (fa/fa) male rats with abnormal oral glucose tolerance associated with initial hyperinsulinaemia as well as control lean (FA/FA) rats were investigated for the development of retinal microangiopathies. The animals were kept on a standard or sucrose supplemented diet. When tested at 60 weeks, the glucose intolerance of fa/fa rats was accompanied by an insulin response that was now either comparable to that of lean rats (standard diet) or close to nil (sucrose supplemented diet). At killing (68 weeks of age), retinal vasculature was examined by electron microscopy and morphological changes were quantitatively assessed by ultrastructural morphometry. A retinal microangiopathy was observed in all mutant animals which was more pronounced in the sucrose fed group, and which was characterized by: (1), an increase in focal thickenings and in nodules of the basement membrane adjacent to the perivascular glial cells; (2), a decrease in the number of pericyte nulei with concomitant signs of early degenerative cytoplasmic changes of pericytes; (3), an increase in the pinocytic activity of endothelial cells, indicative of presumptive changes in vascular permeability; (4), an increase in the number of intercellular endothelial junctions; (5), the presence of numerous stimulated platelets within capillaries. The fa/fa rat may thus be considered as a suitable model for studying the pathophysiology of ocular complications, in particular retinopathy accompanying non-insulin-dependent diabetes.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Neuropeptide Y ; intracerebroventricular ; obese (ob) gene ; ob mRNA ; insulinaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of this work was to determine the possible inter-relationship between neuropeptide Y (NPY, a hypothalamic stimulator of feeding) and adipose tissue expression of the ob protein (a novel potent inhibitor of feeding). Such a relationship could be of importance in the maintenance of normal body weight. To this end, normal rats were intracerebro-ventricularly (i.c.v.) infused for 6 days with NPY. NPY infusion resulted in hyperphagia and a marked increase in adipose tissue ob mRNA levels. The effect of NPY on ob expression persisted when hyperphagia was prevented by pair-feeding, and was reversed following cessation of NPY infusion. Basal and glucose-stimulated insulinaemia were increased by i. c. v. NPY infusion compared to control values, regardless of whether animals were ad libitum-fed or pair-fed. Cessation of NPY infusion was accompanied by normalisation of insulinaemia. These changes in insulinaemia produced by i. c. v. NPY infusion paralleled the observed changes in ob expression. When normal rats were made hyperinsulinaemic-euglycaemic for 24 h, such hyperinsulinaemia also resulted in increased ob mRNA levels in white adipose tissue. This suggested that NPY-induced hyperinsulinaemia could be responsible for the upregulation of ob mRNA levels of NPY-infused rats. It is concluded that central (i. c. v.) NPY infusion increases adipose tissue ob expression, a functional relationship that is linked, at least in part, via NPY-induced hyperinsulinaemia.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Keywords Intracerebroventricular ; neuropeptide Y ; hypothalamo-pituitary adrenal axis ; insulin ; proinsulin ; vagus nerve ; glucose utilisation.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Neuropeptide Y in the hypothalamus is a potent physiological stimulator of feeding, and may contribute to the characteristic metabolic defects of obesity when hypothalamic levels remain chronically elevated. Since corticosterone and insulin are important regulators of fuel metabolism, the longitudinal effects of chronic (6 days) intracerebroventricular infusion of neuropeptide Y in normal rats on the hypothalamo-pituitary-adrenal axis and on insulin secretion were studied. Neuropeptide Y-infused rats were either allowed to eat ad libitum, or were pair-fed with normophagic control rats. Neuropeptide Y increased the basal plasma concentrations of adrenocorticotropic hormone and corticosterone during the first 2 days of its intracerebroventricular infusion and increased cold stress-induced plasma adrenocorticotropic hormone concentrations. After 4–6 days of central neuropeptide Y infusion, however, basal plasma adrenocorticotropic hormone and corticosterone concentrations were no different from control values (except in ad libitum-fed rats in which corticosteronaemia remained elevated), they were unaffected by the stress of cold exposure, and the hypothalamic content of corticotropin-releasing factor immunoreactivity was significantly decreased. A state of hyperinsulinaemia was present throughout the 6 days of intracerebroventricular neuropeptide Y infusion, being more marked in the ad libitum-fed than in the pair-fed group. The proportions of insulin, proinsulin, and conversion intermediates in plasma and pancreas were unchanged. Hyperinsulinaemia of the pair-fed neuropeptide Y-infused rats was accompanied by muscle insulin resistance and white adipose tissue insulin hyperresponsiveness, as assessed by the in vivo uptake of 2-deoxyglucose. Finally, bilateral subdiaphragmatic vagotomy prevented both the basal and the marked glucose-induced hyperinsulinaemia of animals chronically infused with neuropeptide Y, demonstrating that central neuropeptide Y-induced hyperinsulinaemia is mediated by the parasympathetic nervous system. [Diabetologia (1997) 40: 1269–1277]
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Keywords Neuropeptide Y ; intracerebroventricular ; obese (ob) gene ; ob mRNA ; insulinaemia.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of this work was to determine the possible inter-relationship between neuropeptide Y (NPY, a hypothalamic stimulator of feeding) and adipose tissue expression of the ob protein (a novel potent inhibitor of feeding). Such a relationship could be of importance in the maintenance of normal body weight. To this end, normal rats were intracerebroventricularly (i. c. v.) infused for 6 days with NPY. NPY infusion resulted in hyperphagia and a marked increase in adipose tissue ob mRNA levels. The effect of NPY on ob expression persisted when hyperphagia was prevented by pair-feeding, and was reversed following cessation of NPY infusion. Basal and glucose-stimulated insulinaemia were increased by i. c. v. NPY infusion compared to control values, regardless of whether animals were ad libitum-fed or pair-fed. Cessation of NPY infusion was accompanied by normalisation of insulinaemia. These changes in insulinaemia produced by i. c. v. NPY infusion paralleled the observed changes in ob expression. When normal rats were made hyperinsulinaemic-euglycaemic for 24 h, such hyperinsulinaemia also resulted in increased ob mRNA levels in white adipose tissue. This suggested that NPY-induced hyperinsulinaemia could be responsible for the upregulation of ob mRNA levels of NPY-infused rats. It is concluded that central (i. c. v.) NPY infusion increases adipose tissue ob expression, a functional relationship that is linked, at least in part, via NPY-induced hyperinsulinaemia. [Diabetologia (1996) 39: 353–356]
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Intracerebroventricular (i.c.v.) ; neuropeptide Y (NPY) ; food intake ; body weight gain ; in vivo glucose uptake ; muscle insulin resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Intracerebroventricular neuropeptide Y (NPY) administration to normal rats for 7 days produced a sustained, threefold increase in food intake, resulting in a body weight gain of more than 40 g. Basal plasma insulin and triglyceride levels were increased in NPY-treated compared to vehicle-infused rats by about four- and two-fold, respectively. The glucose utilization index of white adipose tissue, measured by the labelled 2-deoxy-d-glucose technique was four times higher in NPY-treated rats compared to controls. This change was accompanied by an increase in the insulin responsive glucose transporter protein (GLUT 4). In marked contrast, muscle glucose utilization was decreased in NPY-treated compared to vehicle-infused animals. This change was accompanied by an increase in triglyceride content. When NPY-treated rats were prevented from overeating, there was no decrease in muscle glucose uptake, nor was there an increase in muscle triglyceride content. This suggests that muscle insulin resistance of ad libitum-fed NPY-treated rats is due to a glucose-fatty acid (Randle) cycle. When intracerebro-ventricular NPY administration was stopped and rats kept without any treatment for 7 additional days, all the abnormalities brought about by the neuropeptide were normalized. A tonic central effect of NPY is therefore needed to elicit and maintain most of the hormonal and metabolic abnormalities observed in the present study. Such abnormalities are analogous to those seen in the dynamic phase of obesity syndromes in which high hypothalamic NPY levels have been reported.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Key words Intracerebroventricular (i. c. v.) ; neuropeptide Y (NPY) ; food intake ; body weight gain ; in vivo glucose uptake ; muscle insulin resistance.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Intracerebroventricular neuropeptide Y (NPY) administration to normal rats for 7 days produced a sustained, threefold increase in food intake, resulting in a body weight gain of more than 40 g. Basal plasma insulin and triglyceride levels were increased in NPY-treated compared to vehicle-infused rats by about four- and two-fold, respectively. The glucose utilization index of white adipose tissue, measured by the labelled 2-deoxy-d-glucose technique was four times higher in NPY-treated rats compared to controls. This change was accompanied by an increase in the insulin responsive glucose transporter protein (GLUT 4). In marked contrast, muscle glucose utilization was decreased in NPY-treated compared to vehicle-infused animals. This change was accompanied by an increase in triglyceride content. When NPY-treated rats were prevented from overeating, there was no decrease in muscle glucose uptake, nor was there an increase in muscle triglyceride content. This suggests that muscle insulin resistance of ad libitum-fed NPY-treated rats is due to a glucose-fatty acid (Randle) cycle. When intracerebroventricular NPY administration was stopped and rats kept without any treatment for 7 additional days, all the abnormalities brought about by the neuropeptide were normalized. A tonic central effect of NPY is therefore needed to elicit and maintain most of the hormonal and metabolic abnormalities observed in the present study. Such abnormalities are analogous to those seen in the dynamic phase of obesity syndromes in which high hypothalamic NPY levels have been reported. [Diabetologia (1994) 37: 1202–1208]
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Keywords Neuropeptide Y ; insulin secretion ; insulin sensitivity ; leptin ; clamp technique ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Intracerebroventricular administration of neuropeptide Y to normal rats induces a syndrome characterised by obesity, hyperinsulinaemia, insulin resistance and over expression of the adipose tissue ob gene. Little is known about the effect of circulating neuropeptide Y on glucose metabolism, insulin secretion and leptin. We therefore aimed to evaluate the effect of an intravenous infusion of neuropeptide Y on glucose disposal, endogenous glucose production, whole body glycolytic flux, and glucose storage as assessed during euglycaemic hyperinsulinaemic clamp. In addition, the insulin-stimulated glucose utilisation index in individual tissues was measured by the 2-deoxy-[1-3H]-glucose technique. The effect of neuropeptide Y on insulin secretion was evaluated by hyperglycaemic clamp. Infusion did not induce any change in endogenous glucose production during basal conditions or at the end of the clamp. Glucose disposal was significantly increased in the rats given neuropeptide Y compared with controls (27.8 ± 1.3 vs 24.3 ± 1.6 mg · min–1· kg–1; p 〈 0.05) as was the glycolytic flux (18.9 ± 1.6 vs 14.4 ± 0.8 mg · min–1· kg–1; p 〈 0.05), while glucose storage was comparable in the two groups. In skeletal muscle, the glucose utilisation index was increased significantly in rats given neuropeptide Y. The glucose utilisation index in subcutaneous and epididimal adipose tissue was not significantly different between the two groups. Plasma leptin was significantly increased by hyperinsulinaemia, but was not affected by neuropeptide Y infusion. Both the early and late phase of the insulin response to hyperglycaemia were significantly reduced by neuropeptide Y. In conclusion neuropeptide Y infusion may increase insulin-induced glucose disposal in normal rats, accelerating its utilisation through the glycolytic pathway. Neuropeptide Y reduces both phases of the insulin response to hyperglycaemia. [Diabetologia (1998) 41: 1361–1367]
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biosensors and Bioelectronics 6 (1991), S. 31-36 
    ISSN: 0956-5663
    Keywords: amperometric enzyme electrode ; glucose sensor ; in-vivo experiments ; subcutaneous glucose
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Electrical Engineering, Measurement and Control Technology , Physics
    Type of Medium: Electronic Resource
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