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  • 1
    ISSN: 1432-0428
    Keywords: Galactosamine hepatitis ; hyperinsulinaemia ; insulin resistance ; liver plasma membranes ; insulin binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Six to 12 h after IP injection of 400 mg/kg of D-galactosamine in rats a 5-fold increase in plasma insulin was observed. In addition, impaired glucose assimilation was present after an IV load in spite of unchanged fasting glucose levels. In streptozotocin-diabetic rats (100 mg/kg IV) plasma insulin remained diminished 12 h after induction of D-galactosamine hepatitis. Under identical conditions of preparation and incubation, the liver plasma membranes of D-galactosamine-treated rats, in both normal and diabetic states, bound only 40–60% as much insulin per mg of membrane protein as those of the control rats. Scatchard analysis suggested that this was due to a decrease in the number of receptor sites in the membranes of the D-galactosamine-injected rats. No difference in the insulin degrading capacity and in insulin-receptor dissociation of the plasma membranes between control and D-galactosaminetreated groups was found. These data suggest that a reduction in the number of hepatic insulin receptors in galactosamine hepatitis can lead to insulin resistance and hyperinsulinaemia.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1440
    Keywords: Type 2 diabetes ; Secondary failure of sulfonylureas ; Combined therapy insulin/glibenclamide ; Hyperinsulinemia ; C-peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In type 2 diabetes with “secondary failure of sulfonylurea therapy” good metabolic control can seldom be achieved by insulin therapy even with high insulin doses. Hyperinsulinemia however is a possible risk factor of cardiovascular disease in type 2 diabetes. Maintaining the effects of sulfonylurea action insulin should be added in as small amounts as possible to avoid hyperinsulinemia and to ameliorate hyperglycemia. 16 type 2 diabetics with “secondary failure” were treated either with insulin alone (group A;n=8) or with 3.5 mg b.i.d glibenclamide plus small amounts of intermediate insulin (group B;n=8) in a randomised order. After the inpatient period outpatient control was performed monthly up to six months, later on four times a year up to two years. Both groups were comparable with regard to age, duration of diabetes, body weight and metabolic control. The daily insulin dose was 14±2 IU $$(\bar x \pm SEM)$$ after one month and 19±2 IU after two years in group B. In contrast 30±3 IU and 43±5 IU respectively were needed in group A (p〈0.001). All patients B were treated with one daily injection, all patients A needed two injections. Resulting in nearly identical metabolic control in group A basal insulin levels exceeded those in group B after two years significantly (28.6±3.7 vs. 18.6±1.6 mcU/ml;p〈0.01). Endogenous C-peptide response was suppressed in group A compared to group B after inpatient period and after one month (0.12±0.01 vs. 0.49±0.15 and 0.09±0.04 vs. 0.13±0.08 pmol/ml;p〈0.05). The combined therapy of insulin and sulfonylureas demonstrates the benefit of a prolonged sulfonylurea administration in the treatment of type 2 diabetes with “secondary failure”. As compared to common insulin therapy a small amount of exogenous insulin by one daily injection additionally to glibenclamide shows similar improvement in metabolic control. Hyperinsulinemia as a risk factor of macroangiopathy is markedly reduced in patients treated with combined therapy compared to those with insulin alone.
    Type of Medium: Electronic Resource
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