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Biomedical subjects

W Besch

Publications and source records attributed to W Besch.

At least 91 records · Page 5Linked to original sources
PubMed1983

Decrease of glucose-induced insulin secretion of pancreatic rat islets after irradiation in vitro.

Irradiation of pancreatic rat islets up to a dose of 2.5 Gy did neither alter glucose-nor IBMX-induced insulin secretion studied in vitro. The insulin as well as glucagon content of irradiated islets were similar as in the control tissue. This was also true in islets irradiated with 25 Gy which were characterized by a decreased insulin secretion in the presence of glucose and IBMX, respectively. Since we did not find indications of an enhanced hormone output in the radiation medium, we want to suggest that higher irradiation doses affect insulin release of pancreatic islets in vitro. This observation has to be taken into account for application of radioimmunosuppression for transplantation.

Animals↗
PubMed1983

Muscular exercise in type I-diabetics. I. Different metabolic reactions during heavy muscular work in dependence on actual insulin availability.

The present study focussed on the impact of heavy muscular work upon metabolic homeostasis in insulin dependent (type I) diabetics in situations involving a certain degree of hyper- and hypoinsulinemia. 20 juvenile type I-diabetics were compared with 6 nondiabetic healthy subjects. The diabetics were studied in states of hypo-(trial A) and hyperinsulinemia (trial B) at the start of the exercise. Differences in insulin availability resulted from the different times that had elapsed from the last insulin injection (3 hours in trial A and 1 hour in trial B) before the ergometer test started at 7 a.m. Six diabetics out of 20 patients were studied in both trials A and B to establish the reproducibility of metabolic reactions to the exercise. Bicycle ergometer tests were carried out in the upright position at 5 graded steps of 50 W, 75 W, 100 W, 125 W and a load near to exhaustion. Rest periods of five minutes were allowed between these work periods for taking blood samples before and after each work load. Plasma glucose, FFA, glycerol, lactate, alanine, IRI and HCP concentrations were investigated. The blood pressure at rest and during exercise was measured, and the physical working capacity (PWC170) was calculated according to Wahlund on the basis of the heart rate response to exercise. The results of the exercise tests reflect clearly the different metabolic reactions to heavy muscular work despite the relatively slight differences in insulin availability at the start: --Exhausting muscular work during the hypoinsulinemic state resulted in hyperglycemia and exaggerated lipolysis. --Heavy muscular work in a hyperinsulinemic state resulted in a reduced blood glucose level and antilipolytic reactions in comparison to nondiabetics. These findings suggest the great necessity of an adequate insulin availability during heavy muscular work in juvenile type I-diabetics.

Aerobiosis↗
PubMed1983

A stimulatory effect of tolbutamide on the insulin-mediated glucose uptake in subjects with impaired glucose tolerance (IGT).

Several studies have indicated that the long-term effectiveness of sulfonylurea therapy in the treatment of type-II diabetics is due to a potentiation of insulin action. The present investigation was undertaken in order to elucidate whether or not there is also an acute effect of sulfonylureas on insulin-mediated glucose uptake. Nine non-obese subjects classified as having impaired glucose tolerance formed the study group. In vivo insulin sensitivity was assessed by using the glucose controlled insulin infusion system (Biostator) without or with a contemporary 3-hour tolbutamide infusion. Studies were performed on subsequent days, and each subject served as its own control. Glucose was given at a fixed rate of 0.011 mmol/kg b.w./min. The computer program was set to maintain plasma glucose concentration at 3.89 mmol/l. The amount of exogenous insulin necessary to keep glycemia at this steady-state level has been accepted as an estimate of insulin sensitivity. Mean plasma glucose and insulin concentrations were constant and comparable in control and sulfonylurea treated groups. Under our experimental conditions tolbutamide did not provoke any increase of C-peptide secretion. There was no significant alteration of insulin counterregulatory hormones (glucagon and growth hormone) either. On the other hand, for the disposal of identical quantities of glucose the necessary amount of insulin has been found to be reduced by one third due to tolbutamide treatment indicating a higher insulin sensitivity. The mechanism by which tolbutamide intensifies the insulin effect is unknown. It seems to be that a successful short-term sulfonylurea therapy on glucose utilization is associated with some alterations on the receptor and/or post-receptor level.

Blood Glucose↗
PubMed1982

Insulin antibodies in juvenile diabetes mellitus. Correlations to diabetic stability, insulin requirement and duration of insulin treatment.

We investigated the plasma insulin binding patterns of 15 insulin-treated juvenile diabetics with a very low residual B-cell function. Determination of the insulin binding was performed after removal of therapeutic insulin. 125I-monoiodoinsulin was used and insulin binding was measured over a large range of insulin concentration. Insulin binding parameters were evaluated by Scatchard analysis of the binding data. Significantly elevated insulin binding was detected when the diabetic control was stable. These patients had a lower insulin requirement and low equilibrium dissociation constants of the high affinity antibodies. Furthermore, a strong negative correlation between the duration of insulin treatment and insulin binding could be demonstrated resulting from both decreasing antibody affinities and maximum binding capacities. We discuss the stabilizing effect of insulin antibodies on the metabolic character assuming that dissociating insulin-antibody complexes mimic a "basal insulin secretion" similar to pancreatic B-cells with residual functional capacity.

Adolescent↗
PubMed1982

Discrepant effect of the prostaglandin synthesis inhibitor acetylsalicylic acid on insulin and C-peptide response to glucose in man.

The prostaglandin synthesis inhibitor acetylsalicylic acid (ASA) increases acute insulin response to glucose and improves glucose tolerance in man. In an effort to provide further information on the mechanism whereby ASA improves glucose tolerance, we studied the effect of ASA on C-peptide, insulin, pancreatic glucagon (IRG), growth hormone (HGH), nonesterified fatty acids (NEFA) and glycerol responses to glucose in 11 non-obese subjects with impaired glucose tolerance. The glucose tolerance was evaluated by means of a 2 h-glucose infusion test. A daily treatment with 3.0 g ASA over 3 days caused a significant increase of acute (delta IRI area 0-5 min) and late (delta IRI area 30-120 min) insulin response and an improvement of glucose tolerance. By contrast, C-peptide response was in the same range prior to and after ASA treatment. Thus, the C-peptide/insulin ratio was decreased by about 50% due to ASA treatment. IRG, HGH, NEFA and glycerol responses to glucose were not altered by ASA treatment. In summary, the discrepant effect of ASA on C-peptide and insulin responses suggest that changes of insulin metabolism may be involved in the mechanism of ASA induced increase in peripheral insulin levels. The improvement of glucose tolerance after ASA application seems to be related to the biologic effect of higher circulating insulin levels but not to alteration of insulin antagonists, such as IRG, HGH and NEFA.

Adult↗
PubMed1982

Pancreatic islet cell suspensions of newborn rats and the formation of pseudo-islets in culture.

Well preserved pancreatic islet cell suspensions were isolated by trypsin treatment from islets of Langerhans of newborn rats. (Pro)insulin biosynthesis of freshly isolated islet cells can be stimulated by increasing glucose concentrations. In contrast insulin secretion on glucose as the only stimulus is drastically reduced but can be potentiated by 3-isobutyl-1-methylxanthine (IBMX). Within a period of 4-6 days in tissue culture pancreatic islet cells of newborn rats show the tendency to aggregate and form pseudo-islets of different size.

1-Methyl-3-isobutylxanthine↗
PubMed1982

Effect of acetylsalicylic acid on insulin sensitivity in subjects with impaired glucose tolerance.

The effect of acetylsalicylic acid (ASA) on tissue sensitivity to insulin was studied in 14 non-obese subjects with impaired glucose tolerance. For the determination of insulin sensitivity a 1 h priming dose-constant insulin infusion technique was used. The percent decrease of plasma glucose and non-esterified fatty acid (NEFA) concentration at comparable steady-state insulin levels was taken as a measure of body sensitivity to insulin. Patients were restudied after daily treatment with 3.0 g ASA over 3 days. The decrease in plasma glucose and NEFA concentration was in the same range prior to and after ASA treatment (20.1 +/- 3.4 vs 20.8 +/- 4.9% and 54.2 +/- 4.8 vs 54.2 +/- 5.4%), indicating no change of insulin sensitivity by ASA treatment. The mean C-peptide concentration during the insulin infusion test did not differ between the two studies. The metabolic clearance rate of insulin was slightly reduced and the disappearance time of insulin was increased after treatment with ASA. In conclusion ASA did not exert any effect on tissue sensitivity to insulin in subjects with impaired glucose tolerance.

Adult↗
PubMed1982

Correlations between the presence of islet cell surface antibodies in human serum and the cytotoxic effects on rat islet beta-cells.

Isolated pancreatic islets from 7-10 days old Wistar rats were incubated in freshly prepared human serum. The cytotoxic insulin leakage from the islets was correlated with the presence in the sera of islet cell surface antibodies (ICSA) determined by indirect immunofluorescence. Such cytotoxic ICSA were found to be common in Type-I diabetics as well as in nondiabetic subjects who had contact with laboratory rats.

Animals↗
PubMed1982

Characterization of beta-cell specific function of isolated pancreatic islets from hyperglycemic C57BL/KsJ-db/db mice.

Isolated pancreatic islets from male hyperglycemic C57BL/KsJ-db/db mice were used to study (pro)insulin biosynthesis, insulin release and insulin content. A diminution of the insulin content to about 36% and of the insulin release (20 mmol/l glucose) to nearly one half was observed, whereas [3H]leucine incorporation into (pro)insulin was increased. Insulin biosynthesis as well as insulin release showed no further increase, when the glucose concentration was increased to 20 or 30 mmol/l. Cultivation of such islets in TCM 199 (10 mmol/l glucose or additionally increased [Mg++] to 5.3 mmol/l) for 48 h resulted in a significant increase of the insulin content and a restoration of the glucose dependent insulin release.

Animals↗
PubMed1982

The effect of litter size on the development of the endocrine rat pancreas.

The influence of litter size on the development of the endocrine rat pancreas in the fetal period has been investigated. Rats from 3 spontaneously different litter sizes were chosen to estimate sex, body weight, food uptake, pancreatic wet weight, insulin and glucagon concentrations, plasma glucose and insulin. With increasing litter size we could observe an enhancement of the pancreatic insulin concentration whereas the glucagon content was decreased. Food uptake caused an increase of insulin and glucagon in the pancreas. The observed changes were not sex dependent. Our results show that the litter size has an obvious effect on the endocrine pancreas already in the fetal and early neonatal phase of development.

Animals↗
PubMed1981

Evaluation of insulin resistance during inhibition of endogenous insulin and glucagon secretion by somatostatin in non-obese subjects with impaired glucose tolerance.

Insulin resistance was studied in seven non-obese male subjects with impaired glucose tolerance and four healthy, age and body-weight matched male control subjects by means of a continuous intravenous infusion of somatostatin, glucose and insulin over 150 min. Glucose tolerance was evaluated by means of a 2-h glucose infusion test. Endogenous insulin (C-peptide), growth hormone, and glucagon secretion were suppressed by somatostatin in both groups. Steady-state plasma insulin and glucose levels were achieved between 90-135 min. Since similar steady-state levels of exogenous insulin were achieved, the resulting steady-state plasma glucose level provided a direct estimate of the ability of insulin to dispose of the infused glucose. The glucose levels were higher in subjects with impaired glucose tolerance with values of 14.6 +/- 1.8 mmol/l compared with 5.1 +/- 1.2 mmol/l in control subjects (p less than 0.01), thus indicating insulin resistance. There was a direct correlation between the steady-state plasma glucose level and glucose tolerance suggesting that the degree of glucose intolerance is proportional to the degree of insulin resistance. These results revealed that decreased insulin sensitivity is found in non-obese subjects with impaired glucose tolerance.

Adult↗
PubMed1981

[Islet cell culture as a method of short-term preservation before islet transplantation].

Pancreatic islets were isolated by collagenase digestion of the pancreas from inbred Wistar rats and cultured at 20 mmol/l glucose and 5.3 mmol/l Mg++ for 4 days. About 1,000 cultured islets injected into the portal vein normalized the plasma glucose of severe diabetic rats induced by streptozotocin (45 mg/kg body weight). Spontaneous recovery of streptozotocin-treated rats was not observed in diabetic controls. Although the insulin response of transplanted rats after i.v. glucose injection (5 mmol per kg body weight) was significantly below control animals, the amount of insulin released was obviously sufficient to sustain a persisting normoglycemia of fed animals up to 1 year. The sufficient preservation of insulin content (I) and the rapid depletion of amylase content (A) of collagenase-treated pancreas fragments cultured for 48 h resulted in a significant rise in the I/A ratio. Because islet isolation is associated with islet loss, especially in the human pancreas, the short term culture enhances hopefully the possibilities for successful transplantation.

Animals↗
PubMed1981

Characterization of insulin biosynthesis and secretion of pancreatic islets prepared from hyperglycaemic sand rats. II. Investigations of islets after different periods of cultivation.

Cultivation of pancreatic islets of sand rats in the presence of high glucose led to a very high insulin release and to strongly diminished insulin contents independent of the metabolic stage of the sand rats. Changes in the [3H]-leucine incorporation into (pro)insulin were not found in dependence of cultivation.

Animals↗