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  • 1
    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
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    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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  • 3
    ISSN: 1432-0428
    Schlagwort(e): Obese-hyperglycaemic mice ; hyperinsulinaemia ; perfused liver ; lipid metabolism ; carbohydrate metabolism ; lipogenesis ; triglyceride secretion ; ketogenesis ; streptozotocin ; gluconeogenesis ; lipid disorders
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Diabetologia 37 (1994), S. S169 
    ISSN: 1432-0428
    Schlagwort(e): Hyperinsulinaemia ; hypercorticosteronaemia ; glucose and lipid handling ; Neuropeptide Y ; corticotropin-releasing factor ; autonomic nervous system ; insulin resistance ; lipogenesis ; local cerebral glucose utilization
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary To study the impact on glucose handling of the observed hyperinsulinaemia and hypercorticism of the genetically obese fa/fa rats, simplified animal models were used. In the first model, normal rats were exposed to hyperinsulinaemia for 4 days and compared to saline-infused controls. At the end of this experimental period, the acute effect of insulin was assessed during euglycaemic-hyperinsulinaemic clamps. White adipose tissue lipogenic activity was much more insulin responsive in the “insulinized” than in the control groups. Conversely muscles from “insulinized” rats became insulin resistant. Such divergent consequences of prior “insulinization” on white adipose tissue and muscle were corroborated by similar divergent changes in glucose transporter (GLUT 4) mRNA and protein levels in these respective tissues. In the second model, normal rats were exposed to stress levels of corticosterone for 2 days. This resulted in an insulin resistance of all muscle types that was due to an increased glucose-fatty acid cycle, without measurable alteration of the GLUT 4 system. In genetically obese (fa/fa) rats, local cerebral glucose utilization was decreased compared to lean controls. This could be the reason for adaptive changes leading to increased levels in their hypothalamic neuropeptide Y levels and median eminence corticotropin-releasing-factor. Thus, in a third model, neuropeptide Y was administered intracerebroventricularly to normal rats for 7 days. This produced hyperinsulinaemia, hypercorticosteronaemia, as well as most of the metabolic changes observed in the genetically obese fa/fa rats, including muscle insulin resistance. These data together suggest that the aetiology of obesity-insulin resistance of genetically obese rodents has to be searched within the brain, not peripherally.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 5
    ISSN: 1432-0428
    Schlagwort(e): ob/ob mice ; insulin ; streptozotocin ; antiinsulin serum ; adipose tissue ; liver ; lipogenesis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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