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  • 1
    ISSN: 1432-0428
    Schlagwort(e): Obesity ; insulin ; glucose ; non-esterified fatty acids ; glucose turnover ; non-esterified fatty acid turnovers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Eight obese patients and 12 normal individuals underwent a euglycaemic insulin clamp (20 and 40 mU · m2−1 · min−1) along with continuous infusion of 3-3H-glucose and 1-14C-palmitate and indirect calorimetry. Basal plasma glucose concentration (4.7±0.3 vs 4.4±0.2 mmol/l) was similar in the two groups, whereas hepatic glucose production was slightly higher in obese individuals (1.11±0.06 vs 0.84±0.05 mmol/min) in spite of higher plasma insulin levels (17±2 vs 6±1 mU/l; p〈0.01). Insulin inhibition of hepatic glucose production was impaired in obese subjects. Glucose disposal by lean body mass was markedly reduced both at baseline (11.7±1.1 vs 15.6±0.6 μmol · kg−1 · min−1; p〈0.05) and during clamp (15.0±1.1 vs 34.4±2.8 and 26.7±3.9 vs 62.2±2.8 μmol · kg−1 · min−1; p〈0.01) Oxidative (12.2±1.1 vs 17.8±1 and 16.1±1.1 vs 51.1±1.7 μmol · kg−1 · min−1; p〈0.05−0.002) and non-oxidative glucose metabolism (3.9±1.1 vs 15.0±2.8 and 12.8±3.3 vs 38.3±2.2 μmol · kg−1 · min−1; p〈0.01−0.001) were impaired. Basal plasma concentrations of non-esterified fatty acids (635±75 vs 510±71 μmol/l) and blood glycerol (129±17 vs 56±5 μmol/l; p〈0.01) were increased in obese patients. Following hyperinsulinaemia, plasma non-esterified fatty acids (244±79 vs 69±16 and 140±2 vs 36±10 μmol/l; p〈0.01) and blood glycerol levels (79±20 vs 34±6 and 73±22 vs 29±5 μmol/l; p〈0.01) remained higher in obese subjects. Baseline non-esterified fatty acid production rate per kg of fat body mass was significantly larger in normal weight subjects (37.7±6.7 vs 14.0±1.8 μmol/l; p〈0.01) and insulin inhibition was reduced in obese patients (−41±9 vs −74±3 and −53±11 vs −82±3%; p〈0.05). Basal plasma non-esterified fatty acid utilization by lean body mass was similar in the two groups (9.8±0.9 vs 8.8±2.0 μmol · kg−1 · min−1), whereas during clamp it remained higher in obese patients (6.0±1.2 vs 2.8±2.5 and 4.9±1.3 vs 1.5±0.6 μmol · kg−1 · min−1; p〈0.1−0.05). Lipid oxidation was higher in obese individuals in spite of hyperinsulinaemia (3.7±0.3 vs 2.4±0.4 and 2.3±0.4 vs 0.9±0.3 μmol · kg−1 · min−1; p〈0.05− 0.02). An inverse correlation was found between lipid oxidation and glucose oxidation (r=0.82 and 0.93; p〈0.001) and glucose utilization (r=0.54 and 0.83; p〈0.05−0.001) both in obese and control subjects. A correlation between lipid oxidation and non-oxidative glucose metabolism was present only in normal weight individuals (r=0.75; p〈0.01). We conclude that in obesity all tissues (muscles, liver, and adipose tissue) are resistant to insulin action. Insulin resistance involves glucose as well as lipid metabolism.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1432-0428
    Schlagwort(e): Ketone bodies ; non-esterified fatty acids ; epinephrine ; insulin ; stable isotopes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary This study was performed to verify: (1) the ability of different insulin concentrations to restrict the lipolytic and ketogenic responses to exogenous epinephrine administration; (2) whether the ability of insulin to suppress the lipolytic and ketogenic responses during epinephrine administration is impaired in Type 1 (insulin-dependent) diabetic patients. Each subject was infused on separate occasions with insulin at rates of 0.2, 0.4, and 0.8 mU·kg−1·min−1 while normoglycaemic. To avoid indirect adrenergic effects on endocrine pancreas secretions, the so-called “islet clamp” technique was used. Rates of appearance of palmitic acid, acetoacetate, and 3-hydroxybutyrate were simultaneously measured with an infusion of 13C-labelled homologous tracers. After a baseline observation period epinephrine was exogenously administered at a rate of 16 ng·kg−1·min−1. At low insulin levels (20 μU/ml) the lipolytic response of comparable magnitude was detected in normal and Type 1 diabetic patients. However, the ketogenic response was significantly higher in Type 1 diabetic patients. During epinephrine administration, similar plasma glucose increments were observed in the two groups (from 4.74±0.53 to 7.16±0.77 mmol/l (p〈0.05) in Type 1 diabetic patients and from 4.94±0.20 to 7.11±0.38 mmol/l (p〈0.05) in normal subjects, respectively). At intermediate insulin levels (35 μU/ml) no significant differences were found between Type 1 diabetic patients and normal subjects, whereas plasma glucose levels rose from 4.98±0.30 to 6.27±0.66 mmol/l (p〈0.05) in Type 1 diabetic patients, and from 5.05±0.13 to 6.61±0.22 mmol/l (p〈0.05) in normal subjects. At high insulin levels (70 μU/ml) the lipolytic response was detectable only in Type 1 diabetic patients; the ketogenic response was reduced in both groups. During the third clamp, a significant rise in plasma glucose concentration during epinephrine infusion was observed in both groups. In conclusion this study shows that at low insulin levels Type 1 diabetic patients show an increased ketogenic response to epinephrine, despite their normal nonesterified fatty acid response. Instead, high insulin levels are able to restrict the ketogenic response to epinephrine in both normal and Type 1 diabetic subjects, although there is a still detectable lipolytic response in the latter. In the presence of plasma free insulin levels that completely restrict the ketogenic response in the same group, there is still a distinct glycaemic response. Plasma insulin levels in Type 1 diabetic patients are a major determinant of the metabolic response to epinephrine.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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