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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 17 (1979), S. 133-138 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Obese-hyperglycaemic mice ; hyperinsulinaemia ; perfused liver ; lipid metabolism ; carbohydrate metabolism ; lipogenesis ; triglyceride secretion ; ketogenesis ; streptozotocin ; gluconeogenesis ; lipid disorders
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Carbohydrate and lipid metabolism has been studied in perfused livers of lean and obese-hyper-glycaemic(ob/ob) mice. The capacity for gluconeogenesis from lactate or pyruvate was similar in livers of both groups of mice. Incorporation of carbon from labelled pyruvate into hepatic lipids was much higher in livers ofob/ob mice than in those of lean controls. Total lipogenesis, as well as newly synthesized triglyceride secretion by perfused livers, was also estimated, by measuring3H (from3H2O) incorporation into total (i.e. liver + perfusate) and perfusate triglyceride fatty acids. Lipogenesis, both in the absence or in the presence of substrates, was greater in livers ofob/ob mice than in those of lean controls, as was newly synthesized triglyceride secretion. In the absence of oleate in the perfusate, the secretion of unlabelled triglyceride by livers of 06/06 mice was much higher than that of non-obese mice, but it did not increase further upon addition of oleate, as it did in livers of lean controls. Ketone body production by livers ofob/ob mice, perfused with albumin bound oleate, was considerably lower than that observed in control livers. Whenob/ob mice were made relatively insulin deficient by streptozotocin treatment, all these anomalies of lipid metabolism were restored towards normal. It is proposed that hyperinsulinaemia is responsible, at least in part, for the abnormalities in lipogenesis, triglyceride secretion and fatty acid oxidation to ketone bodies observed in livers of the obese-hyperglycaemic mice.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Ventro-medial hypothalamus area (VMH) ; insulin secretion ; rat ; VMH insulin relationship
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin secretion, measured in vivo following an intravenous load of glucose to anaesthetized rats, was markedly increased ten minutes after bilateral electrolytic lesions of the ventromedial hypothalamic (VMH) area when compared to both sham-operated and unoperated controls. The successful lesioning of the VMH area was assessed by the subsequent occurrence of hyperphagia, as estimated by the increase in body weight. It is concluded that the ventromedial hypothalamic area exerts an inhibitory influence upon the secretory activity of the B-cells. Furthermore, the rapid disappearance of such inhibitory influence following lesions of the VMH suggests that this area of the brain may be of importance in the minute to minute regulation of insulin secretion. The precise anatomical location of the hypothalamic “nucleus” (or “nuclei”) involved, as well as the neural or humoral nature of its inhibitory effect upon the endocrine pancreas remain to be elucidated.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Preabsorptive insulin secretion ; cephalic phase insulin response ; taste reactivity ; B-cell denervation ; hepatic islet transplantation ; brain stem ; diencephalon ; hypothalamus ; nucleus of solitary tract ; glucose tolerance ; dietary obesity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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 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.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: ob/ob mice ; insulin ; streptozotocin ; antiinsulin serum ; adipose tissue ; liver ; lipogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary C57BL/6J ob/ob mice are obese, hyperglycaemic and hyperinsulinaemic, and are relatively insensitive to the action of exogenously administered insulin. These animals convert more of an intravenous dose of radioactive glucose to lipids in both adipose tissue and liver than do control mice. The lipogenic capacities of the intestine, skin and remaining carcass however are not greatly different from those of lean mice. While lean mice respond to intravenous insulin with a marked increase in incorporation of labelled glucose into lipids in adipose tissue, obese mice do not. Both lean and obese mice made diabetic with strepto-zotocin have a decreased plasma insulin and convert less glucose to fatty acids than do non-treated mice. This is particularly marked in the case of the adipose tissue of obese mice. Similarly, reduction of insulin levels by the injection of anti-insulin serum also caused a decreased lipogenesis which was particularly marked in the case of obese mice. It is postulated that part of the increased lipogenesis seen in ob/ob mice may be due to the abnormally high circulating insulin levels in these mice.
    Type of Medium: Electronic Resource
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  • 7
    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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  • 8
    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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  • 9
    ISSN: 1432-0428
    Keywords: Perfused heart ; genetically obese (fa/fa) rats ; glucose transport ; glucose transporters ; cytochalasin B assay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The regulation of glucose transport in normal and insulin-resistant obese rat hearts have been studied by measuring glucose transport via the efflux of labelled 3-0-methyl-D-glucose. Glucose transporters in obese rat hearts were also investigated using the labelled cytochalasin B-binding assay. Basal, and insulin — or increasing workload-induced stimulation of glucose transport was decreased in obese rat hearts compared to those of normal ones. Total number of glucose transporters (plasma membrane plus microsomal ones) was about half that previously reported for normal rat hearts. Insulin or workload favoured the translocation of glucose transporters from an intercellular pool (microsomes) to the plasma membrane, as they do in normal rats. Due to the measured decrease in total number of transporters of obese rat hearts, those present in the plasma membrane (under basal conditions, or following stimulation by insulin or workload) were less than those previously found in normal rat hearts tested under identical conditions. In obese rat hearts, regulation of plasma membrane transporters was perturbed. The Hill coefficient (an index of positive cooperativity amongst glucose transporters) was paradoxically decreased by insulin while leaving affinity values unaltered. The Hill coefficient was unaltered by workload, although the affinity values were increased compared to respective controls. To sum up, obese rat hearts have decreased total transporter number, and although the two stimuli studied favour the translocation of available transporters, they fail to “activate” them adequately once present in the plasma membrane.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Streptozotocin diabetes ; hyperglycaemia ; phlorizin ; insulin treatment ; glucose utilization index ; 2-deoxy-D-glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The relative contribution of hyperglycaemia and hypoinsulinaemia was evaluated in rats made diabetic by streptozotocin administration. Four groups of rats were studied: untreated normal rats; streptozotocin-diabetic; streptozotocin-diabetic treated with phlorizin (0.4 mg/kg body weight per day); streptozotocin-diabetic mildly treated with insulin (0.7 IU/day). In all groups, insulin action (responsiveness) was assessed with the euglycaemic (5.3 mmol/l) hyperinsulinaemic (524 mU/l) clamp technique combined with 3H-2-deoxy-D-glucose method, enabling determination of the glucose utilization index in various tissues. Responsiveness of the overall glucose utilization process to insulin was reduced by 28% in streptozotocin-diabetic rats (12.0±1.2 vs 16.5±0.6 mg·kg−1·min−1, p〈0.001). This was associated with a significant reduction (p〈0.05) in the glucose utilization index in all muscles studied (average=17.0 vs 32.1 ng·mg of tissue−1·min−1), in the heart (19.6 vs 39.5 ng·mg−1·min−1), brown adipose tissue (98.9 vs 178.0 ng·mg−1·min−1), skin (6.4 vs 13.1 ng·mg−1·min−1). Phlorizin treatment normalized plasma glucose levels without affecting those of insulin, and restored overall glucose utilization to normal (16.6±1.0mg·kg−1·min−1). This normalization was accompanied by a normalization of the glucose utilization index in all muscle types studied (29.2 ng·mg−1·min−1), in the heart (50.0ng·mg−1·min−1), brown adipose tissue (157.2 ng·mg−1·min−1), and skin (10.0 ng·mg−1·min−1). White adipose tissue, brain and gut were not affected. Mild insulin treatment with persistent hyperglycaemia was not able to significantly ameliorate glucose disposal (14.5±0.9 mg·kg−1·min−1) or the glucose utilization index of most individual tissues (muscle=18.4; heart=36.2; brown adipose tissue=148.0; skin=7.7 ng· mg−1· min−1). These data show that correction of hyperglycaemia in streptozotocin-diabetic rats normalizes insulin action, while partial correction of the hypoinsulinaemia fails to do so.
    Type of Medium: Electronic Resource
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