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Biomedical subjects

W Besch

Publications and source records attributed to W Besch.

102 records · Page 6Linked to original sources

Assessment of an algorithm for the artificial B-cell using the normal insulin-glucose relationship in diabetic dogs and men.

Insulin secretion rates after glucose loading were calculated from peripheral venous IRI concentrations considering half life and distribution space of exogenous insulin in normal men and dogs. The coefficients of multiple linear regression analysis between insulin secretion rates and plasma glucose (level and order and rate of change) were used as algorithm parameters in glucose-controlled insulin infusions. These were carried out in each dog based on individual estimations before the induction of diabetes but in the diabetic patients based on values derived from a group of normal subjects. Using this formula, nearly normal patterns of glucose and of insulin were observed in diabetic men and dogs under basal conditions and after IV glucose loading but not after meals. This algorithm enables selection of the parameters prospectively. The effect of a parameter combination depends on insulin sensitivity and it should be appropriately adapted. In the diabetic patients there was no predictable influence of the brittle or stable characteristics of the disease nor of insulin antibodies on the glucose curves obtained with glucose controlled insulin infusions.

Adult↗

[Radioligand assay: method and application. II. Effect of glucagon coupling on the production of glucagon antisera with suitable binding parameters for radioimmunoassay].

Glucagon antibodies were produced in rabbits using three immunogenic glucagon conjugates. Glucagon was coupled to bovine serum albumin by difluorodinitrobenzene (DFDNB), carbodiimide (ECDI) or glutardialdehyde. Rabbits immunized with glucagon conjugated to albumin using DFDNB produced sensitive antisera for radioimmunoassay quite specific for pancreatic glucagon. The affinity constant of the best antiserum was approximately 10(11) l/mol. Antisera raised against the two other glucagon-conjugates were significantly less affine. All of these antisera showed inverse binding curves of 126J-glucagon caused by positive cooperatively in dependence upon the antigen/antibody ratio. The race of rabbits used for immunization was without influence on the immune response.

Animals↗

[Radioligand assay: methods and application. V. Mono-125I-insulin: preparation and immunological and biological characterization].

A reproducible method for preparation of 125I-monoiodoinsulin with fully biological activity was developed. Monoiodoinsulin has been prepared from a heterogeneous 125I-iodination mixture by anion exchange chromatography on DEAE-Sephadex A-25 without using any gradient elution technique. The specific radioactivity of 125I-monoiodoinsulin was calculated to 14.3 +/- 0.8 TBq/g, i.e. an iodine content of 1.04 +/- 0.06 atoms per molecule of insulin. Monoiodoinsulin was indistinguishable from native insulin with respect to binding to guinea pig anti-insulin serum, and to insulin receptors of isolated rat adipocytes. The biological potency (96.5 +/- 7.5 per cent of the immunoreactive insulin activity) determined by the conversion of [14C1]-D-glucose to 14CO2 in vitro by rat fat cells was not significantly different from that of native insulin.

Animals↗

Studies on (pro)insulin biosynthesis and secretion of pancreatic islets of sand rats (Psammomys obesus) after different feeding conditions.

It was possible to induce different metabolic states in sand rats of our breeding colony or in newly caught Egyptian sand rats, respectively, by feeding a pellet diet or vegetable diet (green cabbage). Newly captured sand rats fed only on native food were used as reference group (group C). Plasma IRI-level and glucose in vivo and [3H]-leucine incorporation into proinsulin and insulin, insulin secretion and insulin content in vitro were investigated. Sand rats fed on pellet chow and ad libitum (group B) developed a hyperinsulinism and showed higher sensitivity of [3H]-leucine incorporation into proinsulin and insulin to glucose (maximal stimulation at 3 mM) and increased incorporation rates in vitro. Restriction of pellet food to 35-40 kcal/animal/day (group A) lead to changes of all parameters, which were investigated in the same direction as in group B, but to a much smaller extent. Newly captured sand rats, which were fed green cabbage for 4 to 6 weeks divided into two groups: One group (group D1) was comparable to the normal group (C) in IRI levels, glucose levels, glucose sensitivity and amount of [3H]-leucine incorporation. The other group (group D2) tended to group A. Marked changes in insulin content and insulin secretion of isolated pancreatic islets could not be found in any group.

Animals↗

[Insulin binding to isolated cells].

Using mono-125I-insulin the hormone receptor binding on cultivated rat hepatocytes cultivated rat fibroblasts and freshly isolated adipocytes of wistar rat and man were characterized. No specific insulin binding was obtained in the case of long time cultivated hepatocytes. The fibroblasts show a low specific insulin binding with an affinity constant of K = 0.75. 10(9)M-1 and a binding capacity of q = 4000 binding sites per cell, and also an insulin response measureable by the lactate production. In agreement with a strong stimulation effect of insulin on the conversion of glucose to CO2 und triglycerides the freshly isolated adipocytes bind insulin with high affinity and capacity in comparison with the fibroblasts. For the high affinity population of insulin receptors at the adipocytes of wistar rat we found K = 2.8 . 10(9) M-1 and q = 22000 binding sites per cell, whereas 20 per cent of saturation of the receptors cause 90 per cent of the maximal stimulation effect on the bio-conversion of glucose. This shift of the binding curve to higher concentrations may be important for the ability of insulin to regulate the carbohydrate metabolism.

Adipose Tissue↗

In vitro pancreatic B-cell response of hyperinsulinemic rats. Differences between pregnancy and VMH-lesions.

We investigated in vitro the pancreatic B-cell response of hyperinsulinemic animals compared to that of controls with the aim of clarifying if the hyperinsulinemia is related to an alteration of the islet insulin secretion. Hyperinsulinemia was induced by pregnancy (observation at 19.5 days) and electrolytic lesions of the hypothalamic nucleus ventromedialis (2 days after lesion). The kinetics of the glucose dose/response curves (measured during a 60 min incubation period) differed markedly in the two hyperinsulinemic conditions. Whereas the islets from pregnant rats were characterized by a lowered glucose threshold, an enhanced half-maximal and maximal secretion rate, those of lesioned rats showed only an increased half-maximal and maximal secretion response in spite of a comparable islet insulin content. When culturing islets of hyperinsulinemic animals up to 6 days, the insulin secretion of those prepared from VMH-lesioned rats behaved identically to controls, whereas the islets of pregnant rats maintained their enhanced sensitivity at a glucose concentration of 5 mmol/l. These results confirm that the pancreatic B-cell response contributed significantly to the hyperinsulinemia, but different mechanisms are likely to be responsible for the altered B-cell secretion.

Animals↗

[Endocrine pancreas function in rats in the early postnatal period. The effect of feeding and litter size].

The rat pancreatic endocrine region during the early postnatal period was evaluated depending on the litter size. The body and pancreatic weight lowers and the blood glucose content tends to rise alongside with the litter size increasing. Insulin levels are augmented and glucagon content is reduced in the pancreas of newborn rats with the large litter. The feeding of the animals is accompanied by rapid enhancement of the gland hormone concentration. The per cent content of insulin-secreting cells in Langerhans' islets of newborn rats is rather higher than that of adult animals, being dependent on the litter size as well.

Animals↗