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  • Articles: DFG German National Licenses  (4)
  • Insulin receptor  (2)
  • Type 2 (non-insulin-dependent) diabetes  (2)
  • 1
    ISSN: 1432-0428
    Keywords: 3-3H-glucose ; primed-continuous tracer technique ; Type 2 (non-insulin-dependent) diabetes ; basal glucose turnover ; glucose appearance ; glucose disappearance ; steady-state conditions ; Steele's equations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using primed-continuous 3-3H-glucose infusion, basal glucose production rate has been reported to be 140% higher than normal or almost normal in hyperglycaemic patients with Type 2 (non-insulin-dependent) diabetes mellitus. To determine whether these markedly different results could be due to the mode of priming: fixed or adjusted, or the mode of calculation: steady state or non-steady state equations, we studied 11 patients with Type 2 diabetes (fasting plasma glucose 8–20 mmol/l). For 6 h 3-3H-glucose (0.40 μCi/min) was infused preceded by a priming dose of 40 μCi (fixed priming), or 40 μCi · plasma glucose (mmol/l)·5−1 (adjusted priming). In diabetic patients the plasma glucose concentration was not constant but declined 0.52±0.07 mmol·l−1· h−1. Furthermore, the rate of fall was correlated to the fasting plasma glucose concentration (r=0.90, p〈0.01). Thus, the fasting state was not a steady state condition. Using adjusted priming a constant tracer steady state level was obtained within 60 min. In contrast, using fixed priming tracer steady state was not reached within 6 h. The initial tracer level was far below, and increased in time towards the steady state level observed after adjusted priming. Consequently, using Steele's equations after fixed priming, glucose production rates calculated after 90–120 min were overestimated in proportion to fasting hyperglycaemia. In conclusion: The fasting state in patients with Type 2 diabetes is not a steady state condition. Adjusted priming seems most appropriate in Type 2 diabetes. By estimating glucose production 2 h after fixed priming or assuming steady state conditions, most previous studies may have overestimated basal glucose production in Type 2 diabetes in proportion to fasting hyperglycaemia.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Insulin receptor ; phosphotyrosine phosphatases ; insulin resistance ; skeletal muscle ; Zucker rats ; metformin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to measure the phosphotyrosine phosphatase (PTPase) activity in small muscle biopsies, a sandwich-immunofluorescence assay was developed using the phosphorylated human insulin receptor as a substrate, a C-terminal insulin receptor antibody as catching antibody and Europium-labelled anti-phosphotyrosine as detecting antibody. Soluble and particulate muscle fractions were prepared from soleus muscle of obese, diabetic (fa/fa) Zucker rats and their lean littermates (Fa/-). In the soluble muscle fractions of the obese (fa/fa) rats PTPase activity was significantly reduced compared to control (Fa/-) rats (45.2±2.6% vs 61.3±4.7%, p〈0.02). This reduction was completely prevented by 24 days of metformin treatment which decreased plasma glucose and plasma insulin levels. In particulate muscle fractions, however, no difference in PTPase activity was found among any groups of rats examined. These results show that the alterations in soluble PTPase activity in the insulin-resistant, diabetic Zucker rat vary with the abnormality in glucose homeostasis.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes ; obesity ; insulin resistance ; non-oxidative glucose metabolism ; skeletal muscle ; glycogen synthase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to evaluate the importance of a defect in insulin mediated non-oxidative glucose metabolism and glycogen synthase activity in skeletal muscles in obese subjects with and without Type 2 (non-insulin-dependent) diabetes mellitus we studied: 10 lean and 10 obese control subjects and 12 obese diabetic patients using the euglycaemic hyperinsulinaemic clamp technique (basal, 20 mU · (m2)−1 · min−1, 80mU·(m2)−1·min−1) in combination with indirect calorimetry. Muscle biopsies were taken from m. vastus lateralis at each insulin level. We found that non-oxidative glucose metabolism could be stimulated by insulin in all three groups (p〈0.01). The values obtained at the highest insulin levels (around 140 μU/ml) were lower in both obese groups compared to the lean control subjects (118±21, 185±31, 249±14 mg·(m2)−1·min−1 (p〈 0.01)). Insulin stimulation of the glycogen synthase activity at a glucose-6-phosphate concentration of 0.1 mmol/l was absent in both obese groups, while activities increased significantly in the lean control subjects (19.6±4.2% to 45.6±6.8%, p〈 0.01). Glycogen synthase activities at the highest insulin concentrations only differed significantly between lean control subjects and obese diabetic patients (45±7% and 31±5%, p〈 0.05). We conclude that insulin resistance in peripheral tissues in obese subjects with and without Type 2 diabetes may be partly explained by a reduced insulin mediated non-oxidative glucose metabolism and that this abnormality might be due to an absent insulin stimulation of glycogen synthase in skeletal muscles. This enzyme defect is correlated to obesity itself.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Insulin receptor ; monocytes ; thrombocytes ; negative cooperativity ; insulin degradation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have characterized the cellular composition of preparations isolated from peripheral blood by Ficoll-Isopaque gradient centrifugation.125I-insulin binding to every cell type was measured. A highly significantly positive correlation between specific cell binding fraction and the monocyte concentration of the heterogeneous cell suspension was demonstrated. Depletion of monocytes reduced the insulin binding approximately 80%, which confirms previous findings by other investigators. The granulocytes possessed the second highest binding ability, but only one fourteenth of that of monocytes. Compared to the lymphocyte the monocyte had about 25 times greater insulin binding. Also thrombocytes bound insulin and contamination with these meant that their contribution to the total specific cell binding was not negligible. A reduction in these contaminants is essential. We found that insulin binding to erythrocytes was insignificant. A method of calculating the specific insulin binding to monocytes alone is introduced. The monocyte-insulin-receptor possesses specificity. Only an insignificant degradation of receptor bound insulin could be shown. Evidence of negative cooperativity between receptors was found. Consequently monocytes are considered a useful model for insulin receptor studies in man.
    Type of Medium: Electronic Resource
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