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  • 1
    ISSN: 1432-0428
    Keywords: C-peptide ; insulin antibodies ; glucose tolerance ; segmental pancreatic transplantation ; pancreatic transplant rejection ; brittle diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma C-peptide and serum insulin antibody levels were determined in 5 diabetic patients undergoing vascularized pancreatic transplantation. The grafts functioned well at first and exogenous insulin could be withdrawn, but one to 7 weeks later the grafts were rejected. After the transplantation there was an increase in the fasting plasma C-peptide level, and B-cell stimulation with glucose or glucagon evoked a C-peptide response. Healing of ischaemic damage was reflected in an increase in the C-peptide level. During graft rejection the C-peptide level fell. Measurement of plasma C-peptide levels provides a direct index of the B-cell function of the pancreatic graft. After transplantation the insulin antibody level fell exponentially, with an apparent half life of 10–11 days, whereas the level of total IgG was variable. The results indicate that formation of insulin antibodies ceases immediately on removal of the immunogenic stimulus, that is, on withdrawal of xenogeneic insulin.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Somatomedin ; carrier protein ; diabetes complications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The relationship between insulin-like growth factor I (IGF I) and diabetic retinopathy was investigated. This somatomedin circulates bound to at least two large carrier proteins with molecular weights of approximately 150,000 and 35,000. Total and protein binding profiles of insulin-like growth factor I were determined in the serum of 18 patients who had had Type 1 (insulin-dependent) diabetes for 15–20 years, but had no signs of nephropathy and a similar degree of mild subclinical neuropathy. Nine had preproliferative or proliferative retinopathy and 9 had little or no background retinopathy but there was no difference in diabetes duration, insulin doses or glycaemic control between the two groups. In the latter group, the amounts of the somatomedin I and the serum profiles were similar to those in 9 healthy control subjects. In patients with advanced retinopathy, however, binding of insulin-like growth factor I to the carrier proteins was significantly altered. Binding to the low molecular weight protein increased to 140% whereas binding to the large molecular weight protein decreased to 70% of the normal level. In the latter Type 1 diabetic patients total serum insulin-like growth factor I was decreased to 60% of the normal level (p〈0.02). When the alteration in serum profile was adjusted for, the level of somatomedin associated with the small carrier complex was normal whereas that associated with the large carrier complex was reduced by almost 60% in Type 1 diabetic patients with retinopathy. It is proposed that the total circulating somatomedin level is low in advanced diabetic retinopathy. Furthermore, changes in. the carrier binding of insulin-like growth factor I rather than in the total circulating level of the somatomedin may be involved in diabetic retinopathy.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Keywords Fat cell ; catecholamines ; adrenoceptors ; hormone-sensitive lipase ; insulin.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In this study we investigated whether fat cell lipolysis could be involved in the aetiology of obesity by comparing non-obese subjects with (Hob) or without (Hnorm) a family trait for overweight. A family history of obesity was present when at least one of the first-degree relatives had body mass index of 27 kg/m2 or more. Twenty-seven healthy, drug-free non-obese adult subjects were investigated; 13 were Hob and the remaining 14 were Hnorm. Eleven Hob had at least one obese parent. Isolated fat cells from abdominal subcutaneous adipose tissue were incubated in vitro. Glycerol release (lipolysis index), mRNA levels and enzymatic activity of hormone-sensitive lipase and radioligand binding to beta1- and beta2-adrenoceptors were determined. The lipolytic effects of noradrenaline (major endogenous lipolytic agent), isoprenaline (a non-selective beta-adrenoceptor agonist), forskolin (a direct activator of adenylyl cyclase) and dibutyryl cyclic AMP (activating protein kinase and thereby hormone-sensitive lipase) were reduced by about 50 % (p from 0.001 to 0.01). The maximum activity of hormone-sensitive lipase was reduced 50 % in Hob (p 〈 0.05) and correlated with the lipolytic responsiveness of fat cells in the whole population (r = 0.71). However, there was no difference between the groups in steady-state mRNA levels for the enzyme. Beta1-, beta2- and alpha2-adrenoceptor sensitivity as well as beta1- and beta2-adrenoceptor numbers were normal in Hob. Fasting plasma insulin was 49.1 and 32.6 pmol/l, respectively in Hob and Hnorm (p = 0.01). There was, however, no significant correlation between lipolysis in vitro and plasma insulin. Thus, lipolytic catecholamine resistance in fat cells, at least partly due to impaired function of hormone-sensitive lipase, is an adipocyte abnormality associated with a family tendency to obesity [Diabetologia (1996) 39: 921–928].
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Keywords Adipose tissue, BMI, obesity, polymorphism, TNFα gene.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Tumour necrosis factor alpha (TNFα) is a candidate gene for the development of obesity, which in turn is a major risk factor for diabetes mellitus. The aim of our study was to investigate whether a previously known NcoI-sensitive polymorphism (–308 G/A) in the promoter region of the TNFα gene was related to body weight.¶Methods. Genotyping was done in 239 male and 342 female non-diabetic subjects with a marked variation in body mass index (BMI).¶Results. We found three genotypes; AA (n = 13), AG (n = 158) and GG (n = 410). When the material was divided according to sex, allele specific phenotypic differences were confined to women. The female subjects carrying the AA genotype were markedly more obese than both the AG and GG carriers (mean BMI = 41.4 vs 32.3 and 31.7 kg/m2, respectively, p = 0.02). The body fat content of female AA carriers was increased by one-third compared with AG/GG carriers (p = 0.02). We found no differences between genotypes with respect to waist-to-hip ratio, blood pressure or metabolic variables. Among obese female subjects (BMI 〉 27 kg/m2), we also found that the BMI and body fat content of AA carriers (n = 7) were also higher than for AG/GG carriers.¶Conclusion/interpretation. The AA-variant at position –308 in the promoter region of the TNFα gene could be an important genetic factor behind excessive fat accumulation in women. [Diabetologia (2000) 43: 117–120]
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Microdialysis ; glucose monitoring ; subcutaneous ; adipose tissue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The possibility of continuously monitoring the absolute glucose concentration in subcutaneous adipose tissue, using microdialysis of the extracellular water space, was investigated in six Type 1 (insulin-dependent) diabetic patients. By using a large microdialysis probe (30×0.62 mm), and by perfusing with a low flow rate (0.5 μl/min), complete recovery of glucose was attained in vitro. In the patients the dialysis probe was implanted subcutaneously, perfused by a wearable microinfusion pump, and dialysate samples were collected in 60-min fractions over 10 h. The absolute glucose concentration in the tissue dialysate was the same or almost the same as the blood glucose concentration (range 87–101 % of the blood glucose value). The changes in blood glucose were closely paralleled by the variations in adipose tissue glucose (r=0.93, p〈0.01), and the recovery of glucose in the microdialysate remained constant during the 10-h study period. In conclusion, it is possible, using microdialysis, to directly determine the absolute glucose concentration in subcutaneous adipose tissue. Hence, this technique may be used for continuous glucose monitoring in diabetic patients.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Insulin ; glucose ; obesity ; glucose disposal ; insulin secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin responses to intravenous glucose infusion and glucose utilization during hyperinsulinaemic euglycaemic clamp were determined in a large homogeneous group of 65-year-old male subjects. Twenty-eight had untreated Type 2 (non-insulin-dependent) diabetes mellitus and the remaining 44 control subjects had a normal glucose tolerance. Diabetic patients with abdominal obesity displayed peripheral insulin resistance in combination with defective insulin secretion, whereas non-obese diabetic patients showed only a secretory defect. Thus, Type 2 diabetes in obese and non-obese elderly male subjects may take two forms where the cause of hyperglycaemia differs.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 38 (1995), S. 128-128 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Adipose tissue ; beta-adrenoceptors ; alpha-adrenoceptors ; lipolysis ; mRNA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Upper-body obesity is an important risk factor for developing non-insulin dependent diabetes. To investigate the possibility that a lipolysis defect is present in this form of obesity, we examined the adrenergic regulation of lipolysis in abdominal subcutaneous fat cells from 25 women with upper-body obesity and 24 non-obese women. Lipolytic noradrenaline sensitivity (but not the maximum rate of lipolysis) was reduced by 10-fold in obese women (p〈0.01). The noradrenaline resistance could be ascribed to a 10-fold decrease in lipolytic beta2-adrenoceptor sensitivity (p〈0.01). The lipolytic sensitivity of beta1- and alpha2-adrenergic receptors was normal in the obese women. A 70 % reduction in the cell surface density of beta2-adrenoceptors was observed compared to the control subjects (p〈0.01). However, beta1-receptor density as well as steady-state mRNA levels for beta1- and beta2-receptors were normal in obese women. Lipolytic noradrenaline sensitivity correlated inversely with BMI (adjusted r 2=0.76 together with fat cell volume in stepwise regression analysis). The fasting plasma level of free cortisol was 30 % lower in obese compared to non-obese women (p〈0.05) but obesity did not influence resting plasma catecholamine levels. Thus, lipolytic catecholamine resistance is present in abdominal obesity, due to low density of beta2-adrenoceptors, which in its turn may be caused by a post-transcriptional defect in beta2-receptor expression. Whether abnormalities in circulating free cortisol levels have caused the impaired lipolytic function of these receptors in upper-body obesity remains to be established.
    Type of Medium: Electronic Resource
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  • 9
    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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  • 10
    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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