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  • 1
    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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  • 2
    ISSN: 1432-0428
    Keywords: Insulin resistance ; insulin degradation ; diabetes mellitus ; aprotinin ; insulinases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The period before, during and after resistance to subcutaneous insulin in a 20-year-old, non-obese insulin-dependent patient with ‘brittle’ diabetes is documented and clinical observations are correlated with experimental results of insulin degradation in vitro. Treatment with intravenous but not subcutaneous aprotinin markedly reduced subcutaneous insulin requirements. Insulin resistance recurred following cessation of aprotinin. Serum free insulin levels were low during the subcutaneous resistant phase compared with those during the more sensitive phase. Insulin degradation in vitro by adipose tissue and muscle taken from the patient during a resistant phase was increased compared with degradation by tissue taken during a sensitive phase and by tissue from normal subjects. Chromatography of incubation media revealed that during the resistant phase, tissue from the patient degraded insulin to small fragments. It is concluded that, in this patient, insulin resistance was caused by excessive degradation in both muscle and adipose tissue.
    Type of Medium: Electronic Resource
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  • 3
    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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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 89 (1976), S. 651-660 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: D-allose, a glucose analogue, is not metabolized by isolated fatcells and its distribution space at equilibrium in the cells is the same as that of tritiated water. Uptake of allose is inhibited by glucose and 3-0-methylglucose, stimulated by insulin and virtually eliminated by cytochalasin B. Counter transport of allose out of fat-cells against a concentration gradient can be induced by exogenous glucose but not by pyruvate. It is concluded that allose is transported into fat-cells by the same carrier mediated transport system as glucose and that it is a suitable analogue with which to study the glucose transport system. Insulin stimulated allose transport, into or out of the cell, but not basal transport, is inhibited by a brief exposure of isolated fat-cells to exogenous ATP or ADP (but not AMP or AMP-PNP). The antilipolytic effect of insulin is not affected. The ATP inhibition is slowly reversible.It is suggested that ATP phosphorylates a membrane component and thereby blocks transmission of signal from the insulin receptor to the carrier system. Indirect evidence suggests that ATP does not alter the affinity of the insulin or glucose binding sites.Insulin decreases the Km of glucose metabolism to CO2 and lipid in isolated fat-cells and increases the Vmax. However, the hormone has no effect on the Ki of glucose as an inhibitor of allose transport. The glucose analogue, 3-0-methylglucose, also inhibits both glucose metabolism and allose transport. The Ki for both these processes is similar and is not affected by insulin. These results support the view that the effect of insulin on glucose transport is to raise the Vmax without a change in the Km. It appears further that sugar transport is not the major rate limiting step in metabolism at high glucose concentrations in the absence of insulin, or at most glucose concentrations in the presence of the hormone.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
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