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  • 1
    ISSN: 1432-0428
    Keywords: Acetyl-salicylic acid ; indomethacin ; glucose utilization ; insulin sensitivity ; insulin secretion ; insulin clearance ; hepatic glucose production ; Type 2 diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of acetyl-salicylic acid (ASA, 3 g per day for 3 days) on glucose utilization and insulin secretion was studied in healthy volunteers and Type 2 diabetic patients using the hyperglycaemic and euglycaemic insulin clamp technique. When in healthy subjects arterial plasma glucose was acutely raised and maintained at +7 mmol/l above fasting level, the plasma insulin response was enhanced by ASA (70±7 vs. 52±7mU/l), whereas the plasma C-peptide response was identical. Despite higher insulin concentrations, glucose utilization was not significantly altered (control, 61±7; ASA, 65±6μmol·kg−1·min−1) indicating impairment of tissue sensitivity to insulin by ASA. Inhibition of prostaglandin synthesis was not likely to be involved in the effect of ASA, since insulin response and glucose utilization were unchanged following treatment with indomethacin. In the euglycaemic insulin (1 mU·kg−1·min−1) clamp studies, glucose utilization was unaltered by ASA despite higher insulin concentrations achieved during constant insulin infusion (103±4vs. 89±4mU/l). In Type 2 diabetic patients, fasting hyperglycaemia (10.6 ±1.1 mmol/l) and hepatic glucose production (15±2 μmol·kg−1·min−1) fell upon ASA treatment (8.6±0.7 mmol/l; 13±1 μmol·kg−1· min−1). During the hyperglycaemic clamp study, the plasma response of insulin, but not of C-peptide, was enhanced by ASA, whereas tissue sensitivity to insulin was reduced by 30 percent. It is concluded that in healthy and Type 2 diabetic man, ASA impairs tissue sensitivity to the action of insulin. This effect is counterbalanced by an augmented plasma insulin response to glucose, which results from a reduced insulin clearance rate. In Type 2 diabetic patients, the reduction in hepatic glucose production may be responsible for the amelioration of hyperglycaemia following ASA treatment.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; counter-regulatory hormones ; glucagon ; cortisol ; growth hormone ; adrenaline ; insulin ; non-esterified fatty acids ; ketone bodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To evaluate the relative role of “diabetogenic” hormones as insulin antagonists in severe derangements of diabetic control, glucagon, cortisol, growth hormone and adrenaline were administered by continuous intravenous infusion, separately and in combination, to ketosis-prone insulin-dependent diabetics (n=11). The amount of insulin required for the assimilation of a 50 g glucose load during the various hormone infusions was determined by means of an automated glucose-controlled insulin infusion system and used as an index of insulin effectiveness. Raising plasma hormone concentrations acutely into the range seen in severe diabetic states (glucagon 517±70 pg/ml; cortisol 32±3 μg/dl; growth hormone 14±3 ng/ml) did not alter significantly blood glucose profile and insulin requirement (control 11.3±1.1 U; glucagon 11.6±2.0 U; cortisol 11.1±0.4 U; growth hormone 12.9±1.4U), except for adrenaline (plasma level 550±192 pg/ml), which caused a marked rise in blood glucose levels and a threefold increase in insulin demand (31.1±3.7 U). Combined infusion of all hormones did not potentiate significantly the latter effect (38.3±4.7 U). The effectiveness of metabolic control by insulin was assessed by a marked decrease in plasma non-esterified free fatty acids and ketone bodies upon its administration after glucose ingestion in all groups studied. It is concluded that from the hormones investigated within this study adrenaline exerts the strongest diabetogenic action during its short term administration followed by that of growth hormone. Whereas it may well be that over-insulinization of the patients by the glucose controlled insulin infusion system has overcome and disguised the smaller diabetogenic effects of cortisol and glucagon.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Isolated liver perfusion ; insulin resistance ; islet amyloid polypeptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The impact of (pancreatic) islet amyloid polypeptide on glucose metabolism and insulin sensitivity was examined in isolated rat livers perfused in a non-recirculating system. Continuous infusion of 10−7mol/l islet amyloid polypeptide affected neither basal nor glucagon (10−9 mol/l)-stimulated glucose output by livers from fed rats, but it did increase the hepatic cyclic AMP release within 44 min (7.91±12.07 vs control: 0.07±0.03 pmol·100 g body weight−1). The effect of the peptide on the ability of insulin to inhibit glucagon-induced hepatic glycogenolysis was measured in three experimental groups (n = 6). As expected glucagon (7×10−11 mol/l) increased integral hepatic glucose release within 84 min (763.4±161.7 vs −25.7±73.2 μmol · 100 g body weight−1 in the control group, p〈0.001), while insulin (100 mU/l) decreased the glucagon-stimulated glucose production (395.2±180.0 μmol·100 g body weight−1, p〈0.01). Simultaneous infusion of 10−7 mol/l islet amyloid polypeptide however, was not able to reverse insulin-dependent inhibition of glucagon-stimulated hepatic glucose output (370.0±102.5 μmol·100 g body weight−1, NS) or to enhance lactate-induced gluconeogenesis of livers from 24 h fasted rats (n = 8). The glucose production stimulated by 10−9 mol/l glucagon was slightly greater in islet amyloid polypeptide-pre-treated livers than in a control group without addition of islet amyloid polypeptide (5 min: 3.60±3.36 vs 1.67±1.28 μmol·min−1·100 g body weight−1). These results suggest that islet amyloid polypeptide neither directly affects hepatic glycogenolysis nor causes insulin resistance to hormone-sensitive glucose production, but may increase the size of the hepatic glycogen pool by enhancing gluconeogenesis.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; insulin resistance ; euglycaemic hyperinsulinaemic clamp ; intensified insulin therapy ; HbA1c ; near-normoglycaemia ; continuous insulin infusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To determine the impact of both short- and longterm “near-normoglycaemia” on insulin resistance in Type 1 (insulin-dependent) diabetes hepatic glucose production (mg · kg−1 · min−1) and peripheral glucose utilisation (“M-value”, mg · kg−1 · min−1) were estimated during an euglycaemic hyperinsulinaemic clamp (10 mU · kg · min) in patients with either good (HbA1c〈5.8%, groups A and B) or poor (HbA1c〉7.5%, groups C and D) long-term metabolic control (time 〉 12 months) and in healthy subjects (HbA1c: 5.08±0.20%; n=8). To this end blood glucose was stabilized at 6.7 mmol/l by overnight (t=12 h) i.v. regular insulin in groups (n=8 each) A (HbA1c: 5.49±0.46%) and C (HbA1c: 8.83±1.20%),while groups B (HbA1c:5.55±0.19%) andD (HbA1c: 8.51±1.09%) were kept overnight on long-acting insulin without feed-back control of blood glucose before euglycaemic clamping. Thereby, pre-equilibration of blood glucose at 6.7 mmol/l was shown to normalize basal hepatic glucose production (A: 2.27±0.48; C 2.50±0.57 mg · kg−1 · min−1) despite different HbA1c values, whereas basal hepatic glucose production stayed elevated in groups B (3.09±0.38 mg · kg−1 · min−1) and D (3.21±0.58 mg · kg−1 · min−1) with poor actual glycaemia (B: 10.9±4.6; D: 12.1±4.6 mmol/l). To restitute peripheral glucose utilisation close to normal (healthy subjects: 13.99±2.13; A: 12.12±2.67; B: 8.72±3.0; C: 10.27±1.69; D: 7.10±2.31 mg · kg−1 · min−1; healthy subjects vs A: NS; healthy subjects vs B, C, D: p〈0.05) both long-term (HbA1c〈5.8%) and acute nearnormoglycaemia by 12-h i. v. insulin pre-treatment were required (group A). We conclude that good long-term glucose control per se is unable to normalize hepatic and peripheral glucose metabolism in Type 1 diabetic patients unless actual near-normoglycaemia is provided consistently, e.g. by i.v. overnight infusion of regular insulin.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Vanadate ; isolated liver perfusion ; glycogenolysis ; prostaglandins ; insulin resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Vanadium compounds exert insulin-like effects on isolated rat adipocytes and skeletal muscle and improve glucose homeostasis in diabetic rats and mice. However, reports on metabolic actions of vanadium in the liver are still contradictory. Thus, the acute effect of sodium orthovanadate infusion on net glucose production was measured in isolated perfused livers of non-fasting, non-diabetic rats. Continuous infusion (0.2 ml/min; 90 min) of vanadate (10–500 μmol/l) rapidly increased hepatic glucose (p〈0.001), but not cyclic AMP output, reaching peak values after 20 min. The cumulative glucose release displayed concentration dependence with a maximal net effect of 394.3 μmol/100 g body weight and an apparent half-maximal effective vanadate concentration of 19.6 μmol/l. The glycogenolytic response to vanadate was almost completely blocked by 100 mU/l insulin (p〈0.005), by 0.1 mmol/l indomethacin (p〈0.05) and in the absence of Ca2+ (p〈0.001). These results indicate that sodium orthovanadate stimulates glycogenolysis in livers of fed, non-diabetic rats by a Ca2+-dependent mechanism, which may involve the release of prostaglandins.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 60 (1982), S. 823-828 
    ISSN: 1432-1440
    Keywords: Diabetes mellitus ; Plasma norepinephrine ; Blood pressure regulation ; Diabetes mellitus ; Plasmanoradrenalin ; Blutdruckregulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Das Verhalten von Blutdruck, Plus und Plasmanoradrenalin während verschiedener Stimulationsmanöver sympathisch nervöser Aktivität sowie das vaskuläre Reaktionsvermögen auf infundiertes Noradrenalin (50, 100 und 200 ng/kg−1/min−1,t=15 min) wurde bei 17 Diabetikern und 6 gesunden Probanden untersucht. Unterschieden wurden Diabetiker 1) ohne Zeichen autonomer Dysfunktion und ohne periphere Neuropathie (n=6), 2) ohne Zeichen autonomer Dysfunktion jedoch mit schwerer peripherer Neuropathie (n=6) und 3) mit autonomer Dysfunktion, mit (n=3) und ohne (n=2) peripherer Neuropathie. Während eines „Cold pressor tests“ (2 min), mechanischer Hautirritation (10 min) und Orthostase (10 min) zeigten Diabetiker ohne klinische Zeichen autonomer Dysfunktion ein den gesunden Kontrollpersonen vergleichbares Verhalten von Blutdruck, Plus und Plasmanoradrenalin, während Diabetiker mit autonomer Dysfunktion unabhängig vom Bestehen einer peripheren Neuropathie während der Orthostase, nicht jedoch während des „Cold pressor tests“ und mechanischer Hautirritation eine deutlich herabgesetzte Noradrenalinfreisetzung (P〈0.05) aufwiesen. Normalpersonen und Diabetiker ohne autonome Dysfunktion unterschieden sich bezüglich ihres Blutdruckverhaltens während Noradrenalininfusion nicht, während Diabetiker mit autonomer Dysfunktion auf die Verabreichung von exogenem Noradrenalin (200 ng/kg/min) mit einem gegenüber Normalpersonen verstärkten (P〈0.05) Blutdruckanstieg reagierten. Störungen der Noradrenalinfreisetzung und der adrenergen Blutdruckregulation scheinen somit, unabhängig vom Bestehen einer peripheren Neuropathie, nur bei Diabetikern mit klinischen Zeichen autonomer Dysfunktion aufzutreten. Der Nachweis derartiger Störungen gelingt jedoch nur bei Anwendung von Stimuli größerer Intensität wie Orthostase oder Infusion einer hohen Noradrenalindosis.
    Notes: Summary Changes in blood pressure (BP) and plasma norepinephrine (NE) following various stimuli of the sympathetic nervous system were studied in six healthy subjects and in 17 diabetic patients. The latter were subdivided in three groups: (1) six patients with neither peripheral neuropathy nor autonomic dysregulation, (2) six patients with severe peripheral neuropathy without autonomic dysregulation, and (3) five patients with autonomic dysregulation, three of whom suffered also from peripheral neuropathy. The following procedures were performed: (1) cold pressor test (2 min), (2) mechanical irritation of the skin by suction (0.75 kg/cm2, 10 min), (3) orthostasis (10 min), and (4) i.v. infusion of NE (50, 100, 200 ng kg−1 min−1 for 15 min each). Both the stimulated endogenous plasma NE levels and BP response to exogenous NE were the same in normal subjects, in diabetic controls and in diabetics with peripheral neuropathy without autonomic dysregulation. In contrast, diabetics with postural hypotension showed a less pronounced release of NE to standing (P〈0.05), but not to cold pressor test and mechanical skin irritation. Furthermore, they showed increased vasoreactivity to the highest dose (P〈0.05), but not to the lower doses of exogenous NE. Thus NE release and adrenergic BP regulation seem to be altered only in diabetics with clinical signs of autonomic dysregulation. These alterations can only be evaluated when patients are exposed to stimuli of higher intensity, such as orthostasis or infusion of a high NE dose.
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  • 8
    ISSN: 1043-4666
    Keywords: L-arginine ; diabetes mellitus ; interleukins ; plasma interleukin 1α ; plasma interleukin 1β
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 0022-4731
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0167-0115
    Keywords: Glycogenolysis ; Isolated liver perfusion ; Prostaglandin ; Rat
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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