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  • 1
    ISSN: 1432-0428
    Schlagwort(e): Muscle ; glucocorticoids ; insulin resistance ; glucose transport ; glucose transporter ; glucose fatty-acid cycle ; lipid oxidation ; glycogen synthesis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The mechanism by which glucocorticoids induce insulin resistance was studied in normal rats administered for 2 days with corticosterone then tested by euglycaemic hyperinsulinaemic clamps. Corticosterone administration induced a slight hyperglycaemia, hyperinsulinaemia and increased non-esterified fatty acid levels. It impaired insulin-stimulated total glucose utilization (corticosterone 15.7±0.7; controls 24.6±0.8 mg·kg−1·min−1), as well as residual hepatic glucose production (corticosterone 4.9±1.0; controls 2.0±0.7 mg·kg−1·min−1). During the clamps, insulin did not decrease the elevated non-esterified fatty acid levels in corticosterone-administered rats (corticosterone 1.38±0.15, controls 0.22±0.04 mmol/l). Corticosterone administration decreased the in vivo insulin-stimulated glucose utilization index by individual muscles by 62±6%, and the de novo glycogen synthesis by 78±2% (n=8–9 muscles). GLUT4 protein and mRNA levels were either unchanged or slightly increased by corticosterone administration. Inhibition of lipid oxidation by etomoxir prevented corticosterone-induced muscle but not hepatic insulin resistance. In conclusion, glucocorticoid-induced muscle insulin resistance is due to excessive nonesterified fatty acid oxidation, possibly via increased glucose fatty-acid cycle ultimately inhibiting glucose transport, or via decreased glycogen synthesis, or by a direct effect on glucose transporter translocation or activity or both.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Diabetologia 20 (1981), S. 417-425 
    ISSN: 1432-0428
    Schlagwort(e): 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
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1432-0428
    Schlagwort(e): Keywords Neuropeptide Y ; insulin secretion ; insulin sensitivity ; leptin ; clamp technique ; rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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]
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Diabetologia 7 (1971), S. 209-222 
    ISSN: 1432-0428
    Schlagwort(e): Fat cells ; potassium uptake ; amino acid uptake ; protein synthesis ; lipolysis and energy metabolism ; regulation of lipolysis ; glucose metabolism ; ions and intermediary metabolism ; intracellular FFA ; pinocytosis ; lipolytic hormones ; insulin ; insulin secretion ; cyclic AMP and insulin secretion ; energy and insulin secretion ; cations and insulin secretion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 5
    ISSN: 1432-0428
    Schlagwort(e): Ventromedial hypothalamus (VMH) ; isolated perfused pancreas ; insulin secretion ; glucagon secretion ; somatostatin secretion ; methacholine ; atropine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 6
    ISSN: 1432-0428
    Schlagwort(e): Ventro-medial hypothalamus area (VMH) ; insulin secretion ; rat ; VMH insulin relationship
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 7
    ISSN: 1432-0428
    Schlagwort(e): Glucose effects ; insulin effects ; glycogen synthesis ; glycogen degradation ; glycolytic intermediates ; hepatic glucose production
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The action of glucose and of insulin on hepatic glucose production and metabolism has been studied in fed anaesthetized rats during hyperinsulinaemic clamp combined with various steady state levels of glycaemia (6.8±0.1, 9.3±0.1, 11.8±0.1 mmol/l). Hepatic glucose production was measured using constant infusion of D-[6-3H] glucose. At the end of each clamp the liver was freeze clamped, and enzyme activities and metabolites were measured. Hepatic glucose production was totally suppressed in all the groups receiving insulin. In the group with steady-state normoglycaemia, the suppression of hepatic glucose production was accompanied by a decrease in the levels of glucose-6-phosphate, an increase in those of fructose 2,6-bisphosphate and glycolytic intermediates, but without change in glycogen level or glycogen synthase and phosphorylase. In contrast, in the groups with steady-state hyperglycaemia, phosphorylase a was inactivated, and glycogen synthase activated. Under these conditions, glucose-6-phosphate levels were also decreased and those of fructose 2,6-bisphosphate and glycolytic intermediates were higher than in the group with steady-state normoglycaemia. A slight drop in the level of cAMP was also observed which may contribute, with hyperglycaemia, to the inactivation of phosphorylase. Incorporation of tritiated water into liver glycogen paralleled the activation of glycogen synthase and the accumulation of glycogen. The data indicate that, at normoglycaemia, insulin may suppress hepatic glucose production by channeling glucose-6-phosphate into the glycolytic pathway; at higher levels of glycaemia, a decreased rate of glycogenolysis and an increased rate of glycogen synthesis due to phosphorylase a inactivation and synthase activation may contribute to the decreased level of glucose-6-phosphate, and to a sparing and a net synthesis of glycogen.
    Materialart: Digitale Medien
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