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  • insulin  (6)
  • lipolysis  (2)
  • 1
    ISSN: 1432-0428
    Keywords: Insulin-like growth factor I ; insulin ; C-peptide ; glucagon ; cortisol ; adrenaline ; non-esterified fatty acids ; leucine ; Type 2 (non-insulin-dependent) diabetes mellitus ; hypoglycaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin-like growth factor I (65 μg/kg) or insulin (0.1 IU/kg) were injected i.v. on two separate occasions in random order in normal and in Type 2 (non-insulin-dependent) diabetic subjects. Insulin-like growth factor I and insulin injection resulted in identical decrements of plasma glucose concentrations after 30 min but in delayed recovery after insulin-like growth factor I as compared to insulin in both groups (p〈0.05 insulin-like growth factor I vs insulin). Counterregulatory increases in plasma glucagon, adrenaline, cortisol and growth hormone concentrations after hypoglycaemia (1.9±0.2 mmol/l) in normal subjects were blunted after insulin-like growth factor I administration compared to insulin (p〈0.05). Plasma glucose in Type 2 diabetic subjects did not reach hypoglycaemic levels but the acute glucose decrease to 4.5±0.8 mmol/l was associated with significantly lower responses of plasma glucagon and adrenaline but higher cortisol levels after insulin-like growth factor I compared to insulin (p〈0.003). Plasma concentrations of non-esterified fatty acids and leucine decreased similarly after insulin-like growth factor I and insulin in both groups. The present results demonstrate that insulin-like growth factor I is capable of mimicking the acute effects of insulin on metabolic substrates (plasma glucose, non-esterified fatty acids, leucine). The decreases of plasma glucose were similar after both peptides in normal and in diabetic subjects who were presumably insulin resistant. Counterregulatory hormone responses to plasma glucose decrements differed, however, between insulin-like growth factor I and insulin and in the diabetic and the control subjects. After insulin-like growth factor I the increases in adrenaline, cortisol, growth hormone and glucagon were blunted in normal subjects despite slightly lower plasma glucose concentrations.
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  • 2
    ISSN: 1432-0428
    Keywords: Carbohydrate metabolism ; glucose ; fructose ; xylitol ; sorbitol ; glucose-14C oxidation ; gluconeogenesis ; streptozotocin diabetes ; insulin ; parenteral nutrition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé 1. Chez des rats à jeun pendant 24 h, 35–37% d'une forte quantité de glucose, de xylitol ou de fructose marqués injectée par voie intraveineuse, et 20% de sorbitol sont exhalés en six h sous forme de14CO2. 2. Des rats diabétiques par la streptozotocine exhalaient en 6 h 11–18% de ces substrats sous forme de14CO2. Après correction pour les pools différents de glucose, l'oxydation du glucose est semblable chez les deux groupes d'animaux. L'oxydation du glucose en14CO2 semble donc avoir lieu surtout dans des tissus qui ne sont pas sensibles à l'insuline. 3. 39–55% de la dose de chaque substrat étaient excrétés dans l'urine pendant six heures par les rats diabétiques. La différence consìdérable de l'excrétion urinaire du14C entre les rats à jeun et les rats diabétiques est due à l'excrétion de14C sous forme de glucose chez les rats diabétiques. 4. Six heures après l'injection des 4 substrats, des quantités semblables de14C étaient retrouvées dans le sérum, les osazones du sérum, le glycogène et les lipides totaux du foie, et le glycogène du diaphragme dans chaque groupe de rats. Les similitudes du métabolisme des 4 substrats sont probablement dues à la conversion très rapide du xylitol, du sorbitol et du fructose en glucose.
    Abstract: Zusammenfassung 1. 24 Std lang fastende Ratten exhalierten in 6 Std 35–37% einer intravenös verabreichten Menge markierter Glucose, Xylit und Fructose und 20% von Sorbit als14CO2. 2. Streptozotocin-diabetische Ratten exhalierten von derselben Subtratmenge unter gleichen Bedingungen 11–18% als14CO2. Nach Korrektur für die verschiedene Glucose-Poolgröße oxydieren fastende und diabetische Ratten ähnliche Anteile der Zucker zu14CO2. Die CO2 -Produktion aus Glucose scheint deshalb vor allem in Geweben, die nicht insulinempfindlich sind, stattzufinden. 3. Bei diabetischen Ratten betrug der Verlust im Urin nach allen Substraten 39–55% der gegebenen Dosis. Dieser Unterschied zwischen fastenden und diabetischen Ratten ist auf den zusätzlichen Verlust großer Mengen von14C Glucose im Urin zurückzuführen. 4. Sechs Stunden nach Injektion aller vier Substrate wurden ungefähr gleiche Mengen14C im Serum, in den Serum-Osazonen, in Leberglykogen und -totallipiden und im Glykogen des Diaphragma innerhalb beider Tiergruppen gefunden. Der Stoffwechsel aller vier untersuchter Substrate ist offenbar deshalb ähnlich, weil die Ersatzzucker sehr rasch in Glucose umgewandelt werden.
    Notes: Summary 1. 24-h-fasted rats exhaled 35–37% of i.v. administered loads of labelled glucose, xylitol and fructose, and 20% of a sorbitol load as14CO2 within a period of six hours. 2. Streptozotocin-diabetic rats exhaled under similar conditions only 11–18% of these substrates as14CO2. The rate of glucose oxidation was similar in both groups of animals when a correction for the different glucose pool size was applied. It is concluded that glucose oxidation to14CO2 takes place mainly in tissues which are not sensitive to insulin. 3. Urinary excretion of all substrates was 39–55% of the given dose in diabetic rats. The large difference of urinary carbon-14 between fasted and diabetic rats was due to the excretion of glucose-14C by the diabetic rats. 4. Six hours after the administration of all four substrates, similar amounts of carbon-14 were recovered in serum, serum osazones, liver glycogen and total lipids and diaphragm glycogen within each group of animals. It is concluded that the similarities of the metabolism of all substrates is due to the rapid conversion of the substitute sugars to glucose.
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  • 3
    ISSN: 1432-0428
    Keywords: Ketone body turnover ; ketogenesis ; acetone ; lipolysis ; insulin ; diabetes ; glucagon ; somatostatin ; non-esterified fatty acids ; glycerol ; glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To assess the role of glucagon and insulin in the acute regulation of ketone body kinetics in man, somatostatin was administered with various combinations of these hormones by replacement infusions in groups of six to seven normal subjects. Somatostatin-induced insulin and glucagon deficiency produced a threefold increase in total ketone body concentrations within 2 h. This increase was the combined result of enhanced production (71%), and decreased metabolic clearance (32%), as determined by14C-acetoacetate infusions. An associated elevation of non-esterified fatty acids (66%) and glycerol levels occurred. Glucagon replacement (2 ng · kg-1 · min-1) during insulin deficiency failed to enhance ketogenesis or lipolysis but lowered theβ-hydroxybutyrate/acetoacetate concentration ratios. Hyperglycaemia, observed during glucagon administration and insulin deficiency, did not diminish ketone body production or lipolysis. In contrast, insulin replacement (150 μU · kg-1 · min-1) diminished lipolysis, lowered ketone production, and elevated the metabolic clearance rate of ketone bodies. Glucagon infusions (2 and 4 ng · kg-1 · min-1) during somatostatin and insulin replacement did not accelerate ketone body production or raise non-esterified fatty acid levels, but produced a dose-dependent elevation of blood glucose levels. The results suggest that glucagon is not an important ketogenic hormone under the conditions studied.
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  • 4
    ISSN: 1432-0428
    Keywords: Growth hormone ; ketone bodies ; ketogenesis ; nonesterified fatty acids ; glycerol ; diabetes ; insulin ; glucagon ; somatostatin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of physiological elevation of growth hormone levels on ketone body kinetics was determined using a 14C-ketone body tracer technique in normal and acutely insulin-deficient man. Changes of ketone body production and metabolic clearance rates during growth hormone infusion (plasma levels of approximately 25 μg/l) were measured during basal conditions and during heparin-induced elevation of non-esterified fatty acid levels. Growth hormone administration to six subjects fasted overnight resulted in an increase in ketone body production which exceeded that observed in nine control subjects (5.5±0.5 versus 3.1±0.1μmol·kg-1·min-1, p〈0.025) after elevation of plasma non-esterified fatty acids. Growth hormone infusion increased glycerol and non-esterified fatty acid concentrations indicating enhanced lipolysis. During somatostatin-induced acute insulin deficiency (n=7), growth hormone enhanced the increase in total ketone body production observed in six subjects receiving somatostatin alone (8.4±0.8 versus 4.1±0.7μmol·kg-1·min-1, p〈0.01). Total ketone body metabolic clearance decreased by 50% during somatostatin and remained uninfluenced by growth hormone. Non-esterified fatty acids and glycerol levels increased during somatostatin, and growth hormone failed to alter nonesterified fatty acid levels significantly. The results demonstrate a stimulatory effect of high physiological growth hormone levels on ketogenesis which is largely explained by an enhancement of lipolysis and thus increase in substrate supply for ketogenesis. Growth hormone administration during acute insulin deficiency enhanced ketogenesis in the absence of alterations in plasma non-esterified fatty acid levels, suggesting a direct hepatic ketogenic effect.
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  • 5
    ISSN: 1432-0428
    Keywords: Ketone bodies ; ketone body clearance ; β-hydroxybutyrate ; acetoacetate ; ketogenesis ; ketoacidosis ; insulin ; lipolysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of elevated plasma insulin concentration (55±2 mU/l) on peripheral clearance and production of total ketone bodies was determined using 3-14C-acetoacetate tracer infusions. Nine normal subjects were studied twice, once during insulin infusion (20 mU·m−2·min−1), once during basal plasma insulin concentrations (controls). Blood total ketone body concentrations (sum of acetone, acetoacetate and β-hydroxybutyrate) were maintained in both studies at 2 mmol/l by feedback-controlled sodium acetoacetate infusions. The coefficient of variation of total ketone body concentrations during the two clamp studies was 10 and 11% respectively. The sodium acetoacetate infusion rate required during the clamp was 55±4% higher during hyperinsulinaemia than in controls (p〈0.005). This was due to increased total ketone body clearance (8.4±0.7 vs 6.7±0.4 ml·kg−1· min−1, p〈0.015), and to enhanced suppression of ketone body production (p〈0.01). Hyperketonaemia alone decreased ketone body production by 42% and diminished ketone body clearance by 46%, the former being enhanced, the latter being in part antagonised by insulin. Since the plasma insulin concentrations were within those observed in patients treated for diabetic ketoacidosis, the data suggest that the antiketotic effect of insulin therapy results in part from an increase in peripheral ketone body disposal.
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  • 6
    ISSN: 1432-0428
    Keywords: Cholecystokinin blocker ; plasma glucose ; insulin ; C-peptide ; plasma cholecystokinin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cholecystokinin was previously proposed to play an important role in the regulation of postprandial insulin secretion either indirectly, by inhibiting gastric meal emptying, or directly, by acting as an incretin promoting the release of insulin. The aim of this investigation was therefore to clarify the role of endogenous cholecystokinin in the regulation of insulin release and gastric emptying applying the highly potent and specific cholecystokinin receptor antagonist loxiglumide. Five healthy volunteers were examined after an overnight fast. Gastric meal emptying was measured by the double indicator technique using a multiple lumen tube in the duodenum and 99mTc-diethylenetriamine pentaacetate as a meal marker and polyethylene glycol 4000 as a duodenal perfusion marker. Postprandial insulin, C-peptide, cholecystokinin and glucose levels were measured after ingestion of two isocaloric meals of a) Ensure (containing fat, protein and glucose), and b) a pure glucose meal (1.11 mol/l). The meals were given either with an intravenous infusion of loxiglumide (22 μmol·kg−1·h−1) or placebo. The infusion of loxiglumide markedly accelerated the gastric emptying of the mixed meal (area under curve, 5576±352 min vs 3498±109 min; p〈0.001) and the pure glucose meal (area under curve 5662±537 min vs 3551±534 min; p〈0.05). Simultaneously, loxiglumide induced a more rapid rise in postprandial insulin levels after both meals resulting in significantly higher (p〈0.05) insulin levels during the first postprandial hour, but similar insulin levels in the second postprandial hour. Accordingly, we found a close correlation between meal emptying and insulin release (r=0.748, p〈0.01). Integrated insulin and C-peptide levels for the whole 2-h experimental period tended to be higher during loxiglumide infusion, but the difference did not reach statistical significance. Similar plasma glucose levels at all time periods were observed with and without loxiglumide infusion. Higher cholecystokinin levels were measured during loxiglumide infusion after the mixed (p〈0.01) and the pure dextrose (p〈0.05) meals. We conclude that postprandially released cholecystokinin exerts an important role in the regulation of gastric meal emptying and consecutively the postprandial pattern of insulin release. In contrast, no evidence was found for an insulinotropic role for cholecystokinin in man.
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