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Biomedical subjects

J Ostman

Publications and source records attributed to J Ostman.

At least 91 records · Page 5Linked to original sources
PubMed1986

Transfer from porcine insulin to human insulin in insulin-dependent diabetes mellitus: effects on insulin binding to IgG and glycemic control.

Thirty type I diabetic patients who were treated for at least 2 years with a combination of regular and lente monocomponent porcine insulins were allocated in a double-blind study to either continued porcine insulin treatment or a transfer to the corresponding semi-synthetic human insulins. Insulin binding to IgG measured by an immunoelectrophoretic method, was followed at 3-month intervals for 1 year, and did not change after the transfer. The glycemic control, as assessed by hemoglobin A1 levels, tended to deteriorate in the human insulin group during the first 3 months of the trial and then return to the baseline level. It is concluded that a transfer from highly purified porcine insulin to human insulin apparently does not change the insulin binding to IgG in already sensitized patients.

Adult↗
PubMed1986

Effects of physical exercise on insulin absorption in insulin-dependent diabetics. A comparison between human and porcine insulin.

Nine insulin-dependent diabetics with undetectable plasma C-peptide (less than 0.05 nmol l-1) and without insulin antibodies (insulin binding to IgG less than 0.05 Ul-1) received subcutaneous injections of 10 U 125I-labelled soluble human or porcine insulin in the thigh on 2 consecutive days. Disappearance rates of 125I were monitored continuously by external counting and plasma insulin levels were determined during rest for 30 min, bicycle exercise of moderate intensity for 40 min, and 60 min recovery. Subcutaneous blood flow was measured concomitantly in the contralateral thigh by the 133Xenon clearance technique. During the initial period of rest human insulin was absorbed approximately 40% faster than its porcine analogue (first order rate constants 0.37 +/- 0.06 vs 0.27 +/- 0.06% min-1, P less than 0.05) and the increment of the area under the plasma insulin curve was greater after human than after porcine insulin (184 +/- 46 vs 112 +/- 42 mUl-1 min, P less than 0.05). Exercise enhanced the absorption rates for both 125I-insulins to 0.50 +/- 0.06 and 0.48 +/- 0.10% min-1 for human and porcine insulin, respectively (P less than 0.05). This increase was less pronounced for human compared to porcine insulin (49 +/- 19 vs 105 +/- 40%, P = 0.06). During exercise plasma insulin rose to 37 +/- 5 mUl-1 after human and 30 +/- 5 mUl-1 after porcine insulin and the areas under the plasma insulin curves were similar. During the recovery phase the absorption rates decreased slightly compared to the exercise value for both insulins. The blood glucose lowering effect was similar for the two insulins.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1986

Insulin action in human adipose tissue in acromegaly.

The mechanisms underlying insulin resistance in acromegaly were investigated. Adipose tissue was obtained from nine patients with acromegaly who had in vivo insulin resistance and from 14 matched healthy control subjects. Receptor binding and the antilipolytic effect of insulin were determined in isolated fat cells. Insulin-induced glucose oxidation at a physiological hexose concentration was investigated in fat segments. In fat cells obtained from acromegaly patients after an overnight fast, insulin binding at low hormone concentrations was significantly reduced by 20-30%, insulin-induced antilipolysis was unchanged, but glucose oxidation was unresponsive to insulin. Since it has recently been observed that glucose feeding may rapidly modify insulin action in human adipocytes, fat cells were also obtained 60 min after an 100-g oral glucose load. In this situation, insulin binding at low hormone concentrations was further reduced to one-half of that in the control group, and the sensitivity of insulin-induced antilipolysis was markedly decreased in acromegaly. It is concluded that, in the fasting state, the action of insulin on glucose utilization but not on lipolysis is impaired in adipose tissue of acromegalic patients because of a postreceptor defect. After glucose ingestion, the resistance to insulin in acromegaly is further enhanced and antilipolysis is also impaired. Altered coupling between receptor and effector alone or in combination with an additional decrease in receptor binding may explain the enhancement of insulin resistance. These mechanisms may be essential factors in the pathogenesis of insulin resistance in acromegaly.

Acromegaly↗
PubMed1986

Adrenergic regulation of lipolysis in human adipocytes: findings in hyper- and hypothyroidism.

In isolated sc adipocytes removed from hyperthyroid patients, the specific binding of [3H]dihydroalprenolol and [125I]iodocyanopindolol was greater than that in adipocytes from normal subjects. Based on Scatchard analysis of the [125I] iodocyanopindolol data, this difference was due to a significant (P less than 0.01) increase in adrenoceptor number, which was 1.72 +/- 0.18 (+/- SEM) pmol/10(7) cells in the hyperthyroid patients and 0.94 +/- 0.16 pmol/10(7) cells in the normal subjects. When the patients were restudied when they were euthyroid, a significant decrease in the specific binding of the two radioligands was found. In hyperthyroidism, the lipolytic responsiveness (maximum effect) to norepinephrine was increased 5-fold, and that to isopropylnorepinephrine was increased 2-fold. No changes in either the binding of [3H]yohimbine or the antilipolytic effect of clonidine were found. In isolated adipocytes from hypothyroid patients, the specific binding of [3H]dihydroalprenolol and [125I]iodocyanopindolol did not differ from that in the normal subjects. The basal rate of lipolysis (P less than 0.025) and the lipolytic responsiveness to isopropylnorepinephrine (P less than 0.025) were significantly lower than normal, and the response to norepinephrine was almost completely abolished in the hypothyroid state. The sensitivity and responsiveness to clonidine were comparable in the adipocytes of the hypothyroid patients and normal subjects. There was no difference between hypothyroid patients and normal subjects in the binding of [3H]yohimbine. We conclude that the sc adipocytes in hyperthyroidism have beta-adrenergic, but not alpha 2-adrenergic abnormalities. Although there was a moderate increase in the beta-adrenoceptor density in hyperthyroidism, the most important abnormality, namely the increased responsiveness to the catecholamines, seems to be located beyond the receptor level. On the other hand, in hypothyroidism, there was no evidence of changes in either the alpha 2- or the beta-adrenoceptors. The chief abnormality in hypothyroidism, decreased responsiveness to beta-adrenergic agonists, also would appear to be localized beyond the adrenoceptor level.

Adipose Tissue↗
PubMed1986

The catecholamine concentration in central veins of hypertensive patients--an aid not without problems in locating phaeochromocytoma.

The concentrations of adrenaline, noradrenaline and cortisol in blood sampled at routine attempts at catheterization of the adrenal and renal veins, the inferior vena cava and the azygos and hepatic veins were measured in six patients with a phaeochromocytoma and six patients with hypertension due to other causes. In the non-tumour patients the adrenaline and noradrenaline concentrations, compared with normal values for peripheral venous blood, were abnormally high in five out of seven samples from the site of the left adrenal vein but in only one out of seven from the right side. In all the adrenal vein samples with an abnormally high catecholamine concentration the cortisol level was also elevated, and it was at least 100 per cent higher than in samples from the inferior vena cava. This suggests that a high catecholamine concentration linked with an elevated cortisol level is merely an indication of correct adrenal vein sampling and is not necessarily evidence of a tumour. In successful attempts of sampling adrenal venous blood (cortisol levels increased), concentrations of adrenaline and noradrenaline of up to 100 and 20 nmol/l, respectively, can be regarded as normal. From a retrospective analysis of catecholamine levels in the six tumour patients it is clear that owing to the variability of venous drainage from the right adrenal gland, the technique of adrenal venous blood sampling may be unreliable and even misleading in attempts to locate a phaeochromocytoma. This is also true in patients with generally elevated catecholamine levels.

Adrenal Gland Neoplasms↗
PubMed1986

Epidemiology of diabetes mellitus in Sweden. Results of the first year of a prospective study in the population age group 15-34 years.

All newly diagnosed cases of diabetes mellitus aged 15-34 years in Sweden, where the population in this age interval is about 2.3 million, were registered on standardized forms. During 1983, the first year of the study, there were 311 males and 161 females, excluding 280 with gestational diabetes. The annual incidence of diabetes was 26.2 per 100,000 in males and 14.2 in females. The respective figures for type I were 18.5 and 10.1, and for type II 5.7 and 2.9. The incidence of type I diabetes was similar for the four age groups (15-19, 20-24, 25-29, 30-34 years), while for type II it was highest in the oldest group. Types I and II, but not the sexes, differed as regards the cumulative distribution curves of the maximum blood glucose concentration during the first two weeks after diagnosis. The present incidence of diabetes in Sweden is higher, particularly in males than the rates for similar age groups in Oslo (1925-64) and Denmark (1970-77).

Adolescent↗
PubMed1985

Long-term beta 1-selective adrenergic blockade and adrenergic receptors in human subcutaneous adipocytes.

The influence of beta-adrenergic blockade with metoprolol, a beta 1-selective agent, on the adrenergic regulation of lipid mobilization was explored in subcutaneous adipocytes removed from 13 patients with essential hypertension. Treatment with metoprolol, which was associated with adequate beta-adrenergic blockade and an antihypertensive effect, resulted in a significant increase (p less than 0.05) in the binding of the beta-adrenergic antagonist (-)-(3H)-dihydroalprenolol and a 50% increase (p less than 0.01) in the maximum lipolytic response to the beta-adrenergic agonist isopropylnoradrenaline. In 7 patients with normotriglyceridaemia the total plasma triglyceride level increased significantly (p less than 0.025) during metoprolol treatment, a change that was due to an increase in the very low density lipoprotein triglycerides. The findings suggest that chronic treatment with the beta 1-selective adrenergic blocker metoprolol leads to a significant increase in beta-adrenoceptor density and an increase in the lipolytic response to beta-adrenergic agonists. This latter finding may, in some measure, account for the increased plasma triglyceride level observed.

Adipose Tissue↗
PubMed1985

Effect of fasting on insulin receptor binding and insulin action in different human subcutaneous fat depots.

The possible existence of regional variations in fasting-mediated changes on insulin action an human adipose tissue was investigated in vitro. Subcutaneous adipose tissue was obtained from the femoral, abdominal, and gluteal areas of obese but otherwise normal subjects (16 women and 7 men) before and after 7 days of total fasting. Specific insulin receptor binding to isolated fat cells was similar in femoral and abdominal adipose tissues before and after fasting. However, the latter condition was associated with a significant increase in insulin receptor binding at low hormone concentrations (less than 2 nmol/liter) in gluteal adipocytes. Insulin stimulated glucose oxidation in a dose-dependent way in all 3 adipose regions before fasting. In the femoral and gluteal sites after fasting, the maximum insulin effect was significantly decreased, but a dose-dependent insulin effect was still present, and there was no change in insulin sensitivity. However, abdominal adipose tissue after fasting was completely unresponsive to insulin stimulation when the hormone was added in increasing concentrations up to 80 nmol/liter. The results in fasting women were similar to those in the whole study group. In conclusion, there appear to be marked regional variations in fasting-mediated changes in insulin action on glucose metabolism in human adipose tissue. Alterations at the postreceptor level which lead to insulin resistance appear to be of greater importance than the counteracting receptor changes.

Adipose Tissue↗
PubMed1985

Reversal of insulin resistance in adipose tissue of non-insulin-dependent diabetics by treatment with diet and sulphonylurea.

The effect of conventional treatment on insulin action in subcutaneous adipose tissue was studied in 6 patients with non-insulin-dependent diabetes mellitus (NIDDM). Insulin receptor binding and the effect of the hormone on glucose oxidation were determined before and after 6-14 months of treatment with diet plus sulphonylurea. Glycaemic control and in vivo insulin sensitivity were significantly improved by the treatment. Before treatment, the adipocyte insulin receptor binding and the sensitivity to insulin stimulation of adipose tissue glucose oxidation were normal and did not change after treatment. In contrast, the maximum insulin-induced glucose oxidation was markedly decreased before treatment, whereas it was totally normalized after treatment. The conclusion is that insulin resistance in adipose tissue of NIDDM subjects is solely due to post-receptor defects in insulin action. This resistance is completely off-set by conventional treatment with diet plus sulphonylurea.

Adipose Tissue↗
PubMed1985

Pancreatic transplantation in diabetes mellitus: present status.

Between December 1966 and June 1982, 269 transplantations of vascularized pancreas (whole or segmental) were undertaken in 254 diabetic patients throughout the world. Most of the transplantations were performed in patients with end-stage renal disease who also received kidney grafts; a few patients received pancreatic grafts only. About 25% of the pancreatic grafts are still functioning after periods of various lengths, the longest being five years. To the problem of how to handle the exocrine secretion there are two main approaches: 1) occlusion of the duct with a synthetic polymer and 2) pancreatico-enterostomy. A disadvantage of the former procedure is late fibrosis and atrophy of the endocrine tissue. With the latter method duct leakage and fistula development cannot be completely prevented. In either case, vascular complications cause graft failure in about 20% of the operations. The risk of rejection of the graft seems not to differ significantly from that concerning other allogeneic organs, including the kidney and heart. Most of the patients with a functioning pancreatic graft are normoglycemic: they have a normal or near-normal oral or intravenous glucose tolerance and an early insulin response to intravenous glucose tolerance and an early insulin response to intravenous glucose challenge. Whether the improvement of the motor and sensory nerve conduction velocities observed in some patients whose graft has functioned for a long time is due to the reversal of renal insufficiency or to insulin deficiency cannot yet be determined. At present, pancreas transplantation at Huddinge Hospital is performed only in conjunction with renal transplantation in patients with end-stage diabetic renal disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Influence of fasting and refeeding on the antilipolytic effect of insulin in human fat cells obtained from obese subjects.

The antilipolytic effect of insulin was investigated in obese subjects before and after 7 days of total fasting, and 1 h after oral refeeding with 100 g glucose. Isolated fat cells were prepared from subcutaneous gluteal adipose tissue and incubated in vitro. Specific insulin receptor binding and insulin inhibition of basal and isoprenaline-stimulated lipolysis were determined. During the fasting period, a 15% increase (P less than 0.05) in high-affinity insulin binding and a concomitant 3-4-fold increase in insulin sensitivity were noted, and there was a marked enhancement of the maximum insulin-induced inhibition of basal lipolysis, from 4 to 10 mumol of glycerol/10(7) cells/2 h. The maximum insulin-induced inhibition of isoprenaline-induced lipolysis was similar before and after fasting, about 10 mumol/10(7) cells/2 h. Glucose refeeding induced a 30% decrease (P less than 0.02) in high-affinity insulin binding and a 20-60-fold decrease (P less than 0.01) in the sensitivity of the antilipolytic effect of insulin under basal conditions and in the presence of isoprenaline. The maximum antilipolytic effect of insulin, however, was not altered by glucose refeeding. Thus, in the basal state, maximum antilipolytic effect was larger after refeeding as compared with that before fasting. The high-affinity insulin binding and insulin sensitivity were significantly lower after refeeding than before fasting. Before the fasting period, neither the insulin binding nor the antilipolytic effect of the hormone was altered by oral glucose. It is concluded that fasting and glucose refeeding are associated with marked alterations in the antilipolytic effect of insulin on human fat cells of obese subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1985

Prevention of kidney graft diabetic nephropathy by pancreas transplantation in man.

Kidney graft biopsies were performed 2-3 yr after transplantation in eight type I (insulin-dependent) diabetic patients who had previously been subjected to kidney transplantation (six patients) or combined kidney and segmental pancreas transplantation (two patients). In five of the six patients that had undergone only kidney transplantation, light microscopic examination of the graft biopsy revealed changes compatible with diabetic nephropathy, and electron microscopic morphometry showed a thickening of the glomerular basement membrane (GBM). In the two patients who had been subjected to combined pancreas and kidney transplantation, the kidney graft biopsy showed no light microscopic changes suggestive of diabetic nephropathy, and electron microscopy showed no thickening of the GBM. Thus, it appears to be possible to prevent the recurrence of diabetic nephropathy in human kidney allografts by simultaneous pancreas transplantation.

Adolescent↗
PubMed1985

Effects of intravenous and oral glucose administration on insulin action in human fat cells.

The effects of various forms of glucose administration on insulin action were investigated in isolated human fat cells. Subcutaneous (s.c.) adipose tissue was obtained before and (1) 30 min (eight subjects) and 60 min (seven subjects) after an intravenous (i.v.) glucose load, and (2) after a 60-min continuous i.v. glucose infusion (five subjects). In addition, five subjects were reinvestigated before and 60 min after oral glucose ingestion. Lipolysis (glycerol release) and insulin receptor binding were determined. After all forms of i.v. glucose administration, adipocyte insulin binding was significantly reduced by 20% owing to a decrease in the high-affinity binding, whereas the concentrations of insulin producing the half-maximum inhibitions of basal and isoprenaline-induced rates of glycerol release were unaltered. Sixty minutes after oral glucose ingestion, insulin sensitivity increased 7-30-fold (P less than 0.05-0.01) and high-affinity insulin binding increased by 25% (P less than 0.05). The maximum insulin-induced inhibitions of basal and isoprenaline-stimulated lipolysis were not altered after oral or i.v. glucose. The plasma level of glycerol was markedly and rapidly reduced after oral glucose, but the fall was slow and less pronounced after i.v. glucose. It is concluded that oral, but not i.v., glucose administration mediates a rapid increase in the antilipolytic potency of insulin in human fat cells in vitro. This may explain why antilipolysis in vivo is more pronounced after oral than after i.v. glucose challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1985

Nature of the inhibitory effect of collagenase on phosphodiesterase activity.

The level of phosphodiesterase (PDE) activity is lower in collagenase-isolated human fat cells than in adipose tissue fragments. The inhibition is not species-specific since collagenase also inhibits PDE in rat adipose tissue and bovine heart. In subcellular fractions from isolated fat cells, the PDE activities were lowest in the plasma membrane-enriched fractions and highest in the cytosolic fractions. This is opposite to PDE in subcellular fractions obtained from adipose tissue fragments. In dose-response experiments, collagenase inhibited particulate PDE to a much larger extent than it inhibited soluble PDE. The extracellular activities of PDE were completely eliminated by collagenase. Repeated washings or reincubation of the isolated fat cells did not restore the PDE activity. A purified collagenase with low specific protease activity reduced the PDE activity in isolated fat cells to a lesser extent than did a collagenase with high specific protease activities. Collagen and several protease inhibitors were ineffective in preventing the reduction of PDE after exposure to collagenase. It is concluded that nonspecific proteases in the collagenase preparations used for fat cell isolation interact with particulate and soluble PDE causing an irreversible inhibition of PDE activity in isolated fat cells. Of the various forms of PDE, plasma membrane-associated PDE seems most sensitive to collagenase.

3',5'-Cyclic-AMP Phosphodiesterases↗