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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 23 (1982), S. 517-520 
    ISSN: 1432-0428
    Keywords: Insulin deficiency ; insulin receptor ; fat cells ; lipogenesis ; antibody-induced diabetes mellitus ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The influence of antibody-induced insulin deficiency in rats on the insulin binding and insulin sensitivity of adipocytes was studied. Rats were injected intraperitoneally with an insulin antibody preparation; the development of hyperglycaemia was followed and the animals were sacrificed 3 and 5 h after antibody injection. Up to 3 h, no significant change of insulin binding or sensitivity of the adipocytes occurred. At 5 h, cells of antibody-treated rats showed an approximately 40% increased binding capacity compared with untreated rats. The increased binding capacity was accompanied by an approximate two-fold increased sensitivity of the insulin effect on lipogenesis from glucose in these cells.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Sulphonylurea ; rat ; insulin binding ; insulin action ; extrapancreatic effect ; glycogen synthesis ; rat hepatocytes in primary culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of a sulphonylurea, gliquidone, on insulin binding and the insulin induced rate of glycogen synthesis, were studied in rat hepatocytes in primary culture. Hepatocytes were cultured for 48 h. During the second 24 h of this period, the hepatocytes were incubated with or without gliquidone (5 mg/l). The binding of 125I-insulin and the insulin stimulation of glycogen synthesis from 14C-glucose were measured. Gliquidone influenced neither insulin binding nor the basal rate of glycogen synthesis, but it did enhance the effect of insulin on glycogen synthesis. Responsiveness was increased by gliquidone at all insulin concentrations used (10–10,000 mU/l); at 1000 mil/l the drug increased glycogen synthesis from 310 to 430% above the basal rate. Half-maximal stimulation was reached in control cells at an insulin concentration of 95 mU/l and in gliquidone-treated cells at 94 mU/l, which indicates unchanged insulin sensitivity. Based on these experiments with cultured rat hepatocytes it appears that the extrapancreatic action of gliquidone is not mediated by an effect on insulin binding.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-5233
    Keywords: Key words NIDDM ; Biguanides ; Combination therapy ; Insulin treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Unlike other pharmacological therapies used in obese type 2 diabetic patients, metformin has been shown to improve glycemic control with lower insulin levels and not to involve weight gain. We therefore examined the effect of adjunct metformin in 13 severely obese type 2 diabetic patients (BMI 39.3 ± 3.9 kg/m2) in suboptimal glycemic control pretreated with intensified insulin therapy. Patients were randomly assigned to either metformin or placebo treatment (double-blind) for 10 weeks and after a 2 week washout period received the opposite treatment, respectively, for 10 additional weeks. HbA1c decreased comparably during placebo (from 8.1 ± 0.4 to 7.6 ± 0.3%) and metformin (from 8.5 ± 0.4 to 7.4 ± 0.3%, p = 0.29 vs. placebo). Changes in fasting glucose levels were also not different between placebo (from 9.3 ± 0.7 to 9.5 ± 0.7 mM) and metformin (from 10.3 ± 0.5 to 9.5 ± 0.6 mM, p = 0.44 vs. placebo) Total exogenous insulin requirements decreased from 53 ± 10 to 35 ± 7 units during metformin treatment (p = 0.11). Metformin had no effect on body weight and serum triglycerides but marginally decreased serum cholesterol levels (from 239 ± 18 to 211 ± 14 mg/dl, p = 0.005, p = 0.08 vs. placebo). During the oral glucose tolerance test no differences were observed in the areas under the curve for glucose and insulin while that for C-peptide showed a tendency to increase during metformin administration. We conclude that addition of metformin to insulin treatment in severely obese type 2 diabetic patient improves glycemia but no hyperinsulinemia in comparison to intensive insulin therapy alone. With adjunct metformin, ∼30% less exogenous insulin is required. With respect to glycemia and lipids, adjunct metformin can be a reasonable treatment alternative in selective obese patients with type 2 diabetes already on intensive insulin therapy.
    Type of Medium: Electronic Resource
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