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  • 1
    ISSN: 1432-0428
    Keywords: Keywords Hypoglycaemia ; insulin ; carbohydrate metabolism ; microdialysis ; tissue blood flow.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The absolute glucose concentrations in subcutaneous adipose tissue and skeletal muscle were determined with microdialysis in 10 normal-weight, healthy subjects during a standardized hyperinsulinaemic hypoglycaemic clamp. The concentration of tissue dialysate glucose was measured in 15-min fractions and compared with that in arterialized venous plasma. Insulin (0.15 U · kg-1· h−1) was infused i. v. to lower the plasma glucose level to 2.5 mmol/l over 30 min. This level was maintained for 30 min by using a variable glucose infusion. Thereafter, the insulin infusion was stopped and the plasma glucose level was gradually increased to baseline levels over 120 min. During a 60-min basal period, the glucose levels in muscle were 0.6 mmol/l lower than those in plasma (p = 0.002), whereas the levels in adipose tissue and plasma were similar. The glucose nadirs in muscle (1.6 ± 0.1 mmol/l) and adipose tissue (2.0 ± 0.1 mmol/l) were significantly lower than that in plasma (2.4 ± 0.1 mmol/l) (p = 0.001 and 0.02, respectively), and the time-to-nadir was substantially longer in muscle (69 ± 5 min) and adipose tissue (57 ± 2 min) than in plasma (39 ± 3 min) (p = 0.0004). When the insulin infusion was stopped, the increases in adipose tissue and muscle glucose concentrations were delayed by approximately 25 and 45 min, respectively, as compared to the increase in plasma glucose. Thus, it seems that glucose measurements in adipose tissue and muscle more adequately reflect overall tissue homeostasis than do measurements in blood and that clinically relevant tissue glucopenia may be overlooked by conventional blood glucose measurements. [Diabetologia (1997) 40: 1320–1326]
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Keywords Microdialysis ; glycerol ; non-esterified fatty acids ; adrenoceptors ; adipose tissue blood flow.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The adrenergic regulation of adipose tissue lipolysis in response to insulin-induced hypoglycaemia (intravenous infusion of soluble insulin 0.10 IU · kg body weight−1· h−1 until the arterial plasma glucose fell below 2.8 mmol/l) was investigated directly in vivo in 11 insulin-dependent diabetic (IDDM) patients and 12 control subjects, using microdialysis of the extracellular space of abdominal subcutaneous adipose tissue. The tissue glycerol level (lipolysis index) and the escape of ethanol from the perfusion medium (blood flow index) were continuously monitored. During insulin infusion the arterial glucose level was reduced in parallel and the hypoglycaemic nadir was almost identical in the two groups (diabetic patients 2.2 ± 0.1 and control subjects 2.3 ± 0.1 mmol/l). While the maximum response of plasma epinephrine to hypoglycaemia was 30 % lower in diabetic patients than in the control subjects (p 〈 0.05), the glycerol levels in adipose tissue and in plasma, as well as in serum non-esterified fatty acids, increased twice as much in the former as in the latter group following hypoglycaemia (p 〈 0.01). Addition of the beta-adrenoceptor blocker propranolol (10−4 mol/l) to the tissue perfusate almost completely prevented the hypoglycaemia-induced increase in the adipose tissue glycerol level in both groups, whereas in situ perfusion with 10−4 mol/l of the alpha-adrenoceptor blocker phentolamine resulted in an additional increase in the tissue glycerol levels; during alpha-blockade, the glycerol response to hypoglycaemia remained enhanced by threefold in the diabetic patients (p 〈 0.01). In both groups local adipose tissue blood flow increased transiently in a similar way after hypoglycaemia; the increase being inhibited by in situ beta-adrenoceptor blockade. We conclude that both alpha- and beta-adrenergic mechanisms regulate adipose tissue lipolysis in response to hypoglycaemia. In IDDM, lipolysis is markedly enhanced following hypoglycaemia, despite a reduced catecholamine secretory response, because of increased beta-adrenoceptor action in adipose tissue. [Diabetologia (1996) 39: 845–853]
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 40 (1997), S. 1070-1078 
    ISSN: 1432-0428
    Keywords: Keywords Microdialysis ; glycerol ; non-esterified fatty acids ; circadian rhythm ; growth hormone.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It is not clear how circadian lipolysis and circulating concentrations of non-esterified fatty acids (NEFA) are altered in intensively treated insulin-dependent diabetic (IDDM) patients. Ten IDDM patients on an intensive insulin regimen and eight healthy control subjects were investigated under ordinary living conditions for 27 h by microdialysis of subcutaneous adipose tissue. The true tissue glycerol concentration and adipose blood flow changes were monitored as an index of lipolysis. A circadian pattern in adipose tissue lipolysis was observed in both groups, decreasing during the day and increasing during evening-night. The daytime decrease was normal, but the evening-night rise was elevated in IDDM (p = 0.03). Circulating NEFA decreased during the day and increased at night. The latter increase was enhanced threefold in IDDM (p = 0.003) and correlated with fasting glucose levels (r = 0.77). Nocturnal growth hormone (GH) was increased fivefold in IDDM and correlated to nocturnal lipolysis (r = 0.83). Adipose tissue blood flow increased during the night in a similar fashion in both groups. Near-normalization of glucose for 24 h in IDDM did not affect the nocturnal increases in NEFA, GH and lipolysis. In conclusion, a circadian rhythm in lipolysis was found. Increased lipolytic rates during evening-night may at least in part raise nocturnal circulating NEFA. Nocturnal NEFA and lipolysis are further enhanced in IDDM, maybe due to elevated GH, but not to insulinopenia or hyperglycaemia. [Diabetologia (1997) 40: 1070–1078]
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-5233
    Keywords: Type 1 diabetes mellitus ; Tubular sodium handling ; Lithium clearance ; Renal haemodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of insulin on renal haemodynamics and renal sodium handling were studied in eight insulindependent (type 1) diabetic patients (aged 30±3 years). Seven healthy men (aged 38±4 years) served as controls. The type 1 diabetic patients were resistant to insulin-stimulated glucose disposal as estimated by a 45% lower metabolic (P〈0.01) clearance of glucose as compared with controls. However, type 1 diabetic patients were still sensitive to the distal tubular antinatriuretic effect of insulin, as indicated by an increase in distal sodium reabsorption (95.5%±0.5% to 96.9%±0.4%;P〈0.05) during insulin infusion compared with controls (95.5%±0.6% to 97.4%±0.3%;P〈0.05). In control subjects insulin infusion was associated with 9% increases (P〈0.05) in lithium clearance and in renal plasma flow, whereas no significant increases in lithium clearance and in renal plasma flow were observed in the type 1 diabetic patients. In both groups, the changes in renal plasma flow in response to insulin infusion were positively correlated with that in lithium clearance (r=0.80 andr=0.90, respectively;P〈0.05−0.01). In conclusion, the present result demonstrates an intact distal tubular sodium retaining effect in conjunction with a blunted decrease in proximal tubular sodium reabsorption following insulin infusion, which could be the result of an impaired renal vasodilation in type 1 diabetes mellitus.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-5233
    Keywords: Key words Angiotensin-converting enzyme (ACE) inhibition ; Sodium retention ; Renal dopamine ; Atrial natriuretic peptide ; Proximal tubule ; Type 1 diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The objective of the present study was to determine whether acute inhibition of angiotensin converting enzyme (ACE) normalizes intrarenal sodium handling, renal haemodynamics and renal dopamine output in response to an i.v. NaCl infusion in type 1 diabetic patients with early nephropathy. Nine diabetic patients (aged 28±3 years) with elevated urinary albumin excretion (173±39 mg ⋅ min–1) were studied. The effects of a 2-hour NaCl infusion (12.5 ml ⋅ kg–1⋅ h–1) on para-amino hippuric acid (PAH), inulin, lithium and sodium clearances as well as the urinary dopamine excretion were studied before and after 2 days of acute ACE inhibition. Fifteen healthy subjects (aged 34±1 years) served as controls. The results showed that 2 days of ACE inhibition improved the natriuretic response significantly (P〈0.05) within the first 2 h following an i.v. NaCl load due to a normalization of the proximal tubular sodium handling. In control subjects urinary dopamine output increased by 14% (P〈0.01) following i.v. NaCl infusion, whereas a blunted increase was seen in the diabetic patients, which tended to normalize following inhibition of ACE. In conclusion, this study demonstrates that patients with type 1 diabetes and early nephropathy display abnormalities in renal haemodynamics, natriuresis and urinary dopamine mobilization in response to a sodium load, which can be reversed by short-term inhibition of ACE.
    Type of Medium: Electronic Resource
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