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  • 1
    ISSN: 1432-0428
    Keywords: pancreatogenic diabetes ; pancreatectomy ; glucagon ; alanine ; lactate ; pyruvate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary High levels of gluconeogenic precursors have been reported in patients with long-term diabetes secondary to total pancreatectomy. In the present study, blood concentrations of alanine, lactate and pyruvate were measured in six patients undergoing total pancreatectomy and in nine control subjects undergoing major abdominal surgery. To exclude the simple effect of lack of insulin and hyperglycaemia in the development of hyperalaninaemia following total pancreatectomy, three pancreatectomized patients and five control subjects underwent surgical operation while connected to an artificial pancreas. Blood concentration of alanine was constant in the control subjects during surgery (182±20 and 243±31 μmol/l with and without the artificial pancreas, respectively). In pancreatectomized patients basal blood alanine levels were similar to those in control subjects. Blood alanine level rose quickly after removal of the pancreas from 182±24 to 285±15 μmol/l (p〈0.05) in the patients connected to the artificial pancreas, and from 198±17 to 395±47 μmol/l (p〈0.05) in patients undergoing total pancreatectomy without artificial pancreas. These values were higher than those observed in the control subjects at the end of the operation (192±22 and 230±45 μmol/l with and without artificial pancreas, respectively.) Basal and intraoperative blood concentrations of lactate and pyruvate were similar in pancreatectomized patients and control subjects.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Obesity ; insulin ; glucose ; non-esterified fatty acids ; glucose turnover ; non-esterified fatty acid turnovers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-5233
    Keywords: Key words Sulfonylurea ; Gliclazide ; Endogenous glucose production ; Insulin secretion ; Glucose tolerance ; Glucose kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An extrapancreatic effect of sulfonylureas has been postulated. However, in vivo results have been disputed because the amelioration of insulin action that follows sulfonylurea may represent the relief from glucose toxicity rather than a direct effect of the drug. Therefore, we studied the hypoglycemic action of gliclazide acutely and after 2 months of therapy in seven type 2 diabetic patients. All patients received a 240-minute IV glucose infusion with [3-3H]glucose. In a random order, 160 mg gliclazide (study 1) or placebo (study2) was given orally before glucose infusion. Finally, the effect of 160 mg gliclazide was reassessed after a two-month treatment with the same sulfonylurea (80 mg t. i. d.). Basal plasma glucose, insulin, C-peptide and endogenous glucose production (EGP) were similar before the two initial studies. During glucose infusion, EGP was more suppressed after gliclazide in spite of comparable increase in plasma insulin and C-peptide. After the two-month therapy, basal plasma glucose levels and HbA1c were lower while plasma insulin and C-peptide were higher with respect to baseline (p 〈 0.05). Gliclazide further reduced plasma glucose, the incremental area above baseline, and EGP during glucose infusion, while plasma insulin and C-peptide achieved higher plateaus (p 〈 0.05). When data were pooled, plasma glucose concentration and EGP correlated both in the basal state (r = 0.71) and during the last hour of glucose infusion (r = 0.84; both p 〈 0.05). These data suggest that gliclazide enhances the suppression of EGP induced by insulin and that this effect is greater with chronic treatment because of concomitant improvement of insulin secretion.
    Type of Medium: Electronic Resource
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