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Biomedical subjects

O Pedersen

Publications and source records attributed to O Pedersen.

282 records · Page 16Linked to original sources
PubMed1976

A study of insulin receptors in human mononuclear leucocytes.

Insulin binding sites were demonstrated in human mononuclear leucocytes by use of a technique which includes isolation of mononuclear leucocytes from defibrinated blood and separation of cell bound and free [125I]insulin with silicone oil. The binding was time and temperature dependent. At 15 degrees C equilibrium was reached after 90 min and a plateau maintained for at least 50 min. Incubations were carried out at 4 degrees C, 15 degrees C and 37 degrees C. Maximal binding was obtained at 15 degrees C. The optimum pH for insulin receptor interaction occurred at about 8. [125I]insulin binding to mononuclear leucocytes was demonstrated to be a linear function of cell number concentration over a range of 17-70 X 10(6) X ml-1. The binding was a displaceable function of native insulin concentration. In a group of 21 young healthy persons with normal body weight we found a mean specific cell binding fraction of 1.92 +/- 0.58 (s) X 10(-2). Analysis of the equilibrium between insulin and its receptor revealed an apparent heterogeneity of insulin receptors.

Binding Sites↗
PubMed1976

The insulin receptor in normal and obese persons.

Using [125I]insulin at 172 pmol/1 (1 ng/ml) the binding of insulin to mononuclear leucocytes isolated from peripheral blood was studied. Our present study comprised 21 healthy subjects (22-33 years old, 90-110% of ideal weight) and a comparable group of 22 obese subjects (20-37 years old, minimum 150% of ideal weight). A significant difference in insulin binding was found between the two groups, the mean specific insulin binding fraction in normals being 1.92 +/- 0.58 (s) X 10(-2) and that for the obese 1.19 +/- 0.41 (s) X 10(-2) (P less than 0.01). No correlation was found between body weight and the number of insulin receptors in the obese subjects. However, the number of insulin receptors was negatively correlated to fat cell size (P less than 0.05). Insulin receptors in subjects were also negatively correlated to fasting plasma insulin (P less than 0.05). Insulin receptors were studied in 11 obese subjects before and after 10 days of fasting. A significant increase in the number of insulin receptors was observed with a simultaneous decrease in plasma insulin to normal values. The results indicate that obesity complicated by hyperinsulinism is associated with a decrease in the number of insulin receptors compared with the normal. This finding may in part explain the decreased insulin sensitivity of the hyperinsulinaemic obese.

Adult↗
PubMedDate not supplied

Increased insulin binding is not involved in the improved insulin effectiveness of gestational diabetics after hypoenergetic dieting.

125I-Insulin binding to monocytes from 14 gestational diabetics was measured before and after 6 weeks of treatment with a 5500 kJ, low-fat, low-sucrose diet. After the hypoenergetic feeding of gestational diabetics, fasting plasma concentrations of glucose (P less than 0.01) and insulin (P less than 0.05) decreased significantly, whereas insulin binding was unaltered. Provided the monocyte insulin receptor reflects insulin receptors of more determinant tissues for insulin action, our data indicate that an increased insulin receptor binding is not involved in the improved insulin effectiveness of gestational diabetics after hypoenergetic dieting.

Adult↗
PubMedDate not supplied

The effect of chronic hyperglycaemia on the islet B-cell responsiveness in newly diagnosed type 2 diabetes.

The aim of the present study was to evaluate the effect of chronic hyperglycaemia on the pancreatic B-cell response to stimulation with a standard mixed meal or intravenous glucagon in 7 subjects with newly diagnosed Type 2 diabetes. Stimulation was performed at mean chronic fasting hyperglycaemia of 11.8 +/- 0.7 (SEM) mmol l-1 and at normoglycaemia obtained by an intravenous infusion of regular insulin followed by an insulin wash-out period. The incremental plasma C-peptide area under the curve after stimulation with the meal was similar at normo- and hyperglycaemia. In contrast, prestimulatory plasma C-peptide and the incremental plasma C-peptide area under the curve after stimulation with glucagon were significantly higher at chronic hyperglycaemia than at normoglycaemia (p less than 0.01 and p less than 0.05). In conclusion, chronic hyperglycaemia as seen in newly diagnosed Type 2 diabetes is associated with a complete lack of potentiation of postprandial islet B-cell secretion but a partly preserved potentiation of basal and post-glucagon islet B-cell secretion.

Blood Glucose↗
PubMedDate not supplied

Adipocyte insulin binding and action in moderately obese NIDDM patients after dietary control of plasma glucose: reversal of postbinding abnormalities.

Studies of fat cells from patients with newly diagnosed, untreated non-insulin-dependent diabetes mellitus (NIDDM) have revealed severe abnormalities in insulin action on glucose transport and metabolism. To determine whether these defects can be reversed if good glycemic control is reached by dietary treatment, eight moderately obese NIDDM subjects were studied at diagnosis and again when the patients had been in good glycemic control induced by low-energy dieting for at least 2 mo (absence of glycosuria and fasting plasma glucose less than 7 mM). Average body weight decreased by 8 kg (P less than .05). Fasting plasma glucose decreased from 11.5 +/- 1.2 to 6.9 +/- 0.9 mM, whereas fasting serum insulin concentrations were unchanged. Adipocyte insulin binding at tracer concentration (15 pM, 37 degrees C) was not changed significantly (1.94 +/- 0.52 to 2.05 +/- 0.62% per 30 cm2 surface area/ml). The basal (non-insulin-stimulated) glucose transport (tracer glucose concentration 5 microM) increased from 25 +/- 12 to 44 +/- 14 pmol X 90 min-1 X 10 cm-2 surface area (P less than .02). The maximally insulin-stimulated glucose transport rate increased from 35 +/- 20 to 78 +/- 26 pmol/90 min (P less than .01). The percentage insulin response above basal levels increased from 31 +/- 40 to 89 +/- 58% (P less than .01). The insulin sensitivity (half-maximally stimulating insulin concentrations) was also improved (P less than .05). Glucose conversion rates to total lipids increased 34 +/- 62 and 65 +/- 80% in basal cells and maximally insulin-stimulated cells, respectively (.2 greater than P greater than .1, .1 greater than P greater than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMedDate not supplied

Changes in nasal resistance and nasal geometry using pressure and acoustic rhinometry in a feline model of nasal congestion.

This is the first report describing the use and pharmacological characterization of nasal patency by both pressure rhinometry and acoustic rhinometry (AcR) in an experimental cat model of nasal congestion. In pressure rhinometry studies, aerosolized compound 48/80 (0.1-3.0%), a mast cell liberator, increased nasal airway resistance (NAR) 1.2 +/- 0.6, 5.8 +/- 0.5, 8.6 +/- 1.1 and 7.9 +/- 1.5 cmH2O.L/minute, respectively. Increases in NAR produced by compound 48/80 were associated with a 395% increase in histamine concentration found in the nasal lavage fluid. Pretreatment with the alpha-adrenoreceptor agonist, phenylpropanolamine (PPA; 0.1-3.0 mg/kg, i.v.), and the NO synthetase inhibitor, NG-nitro-L-arginine (L-NAME; 10 mg/kg, i.v.) attenuated the increases in NAR produced by compound 48/80. The histamine H1 antagonist chlorpheniramine (1.0 mg/kg, i.v.) and the H2 antagonist, ranitidine (1.0 mg/kg, i.v.) had no decongestant activity. Also without decongestant activity were the muscarinic antagonist atropine, the cyclooxygenase inhibitor indomethacin, and the 5-HT blocker methysergide. Aerosolized histamine (0.1-1.0%) also produced a dose dependent increase in NAR. In studies using acoustic rhinometry (AcR), intranasal application of compound 48/80 (0.1-1.0%) elicited pronounced decreases in nasal cavity volumes and minimum cross-sectional area (Amin). Pretreatment with PPA (3 mg/kg, i.v. or 10 mg/kg, p.o.) attenuated the decreases in nasal volume and Amin. The effects of topical intranasal histamine (0.1-1.0%) on nasal geometry were similar to compound 48/80. We conclude that the cat is a useful model for evaluating the pharmacological actions of potential nasal decongestants. Furthermore, we also conclude that AcR is a useful method for noninvasive assessment of nasal patency in a preclinical setting.

Acoustics↗
PubMedDate not supplied

Sulfonylureas improve insulin binding and insulin action in non-insulin-dependent diabetes mellitus.

Sulfonylureas reduce plasma glucose concentrations in most patients with non-insulin-dependent diabetes mellitus (NIDDM). The mechanism of this action is controversial. In this article we examine the issue of the peripheral effect of these drugs, i.e., the effect on insulin receptors and insulin action. In our studies we have found that sulfonylureas possess a selective regulatory in vivo effect on the cellular insulin binding to monocytes, independent of the diet and changes in plasma glucose and insulin concentrations. Furthermore, we found in in vitro studies that sulfonylureas affect the insulin receptors in a direct way. Thus, insulin binding to monocytes was increased during sulfonylurea treatment in both normal volunteers and patients with NIDDM. On the other hand, sulfonylureas seem to improve insulin action in NIDDM patients only. We conclude that the increased insulin binding in patients with NIDDM, induced by sulfonylurea treatment, may be of importance for the improved insulin action found in these patients. However, this hypothesis has to be proved.

Binding, Competitive↗