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Biomedical subjects

W Besch

Publications and source records attributed to W Besch.

At least 73 records · Page 4Linked to original sources

Serum magnesium in insulin-dependent diabetics and healthy subjects in relation to insulin secretion and glycemia during glucose-glucagon test.

UNLABELLED: In order to investigate the influence of insulin secretion on serum magnesium concentrations 33 insulin-dependent diabetics and 10 control subjects were studied. The residual insulin secretion (RIS) was investigated by measurement of human C-peptide (HCP) before and after stimulation during on OGTT (1.75 mg/kg)-glucagon (i.v. 0.1 mg glucagon/kg)-test. RESULTS: Certain RIS existed in 11 insulin-dependent diabetics, 12 were without any RIS (uncertain RIS in 10 patients). Glucose tolerance and daily glycemia differed significantly among the two groups. However, all diabetics were far from euglycemia, (3.3-9.3 mmol/l): Fasting plasma glucose 12.0 +/- 0.9 (certain RIS), 15.0 +/- 0.8 (no RIS), 13.9 +/- 1.8 (uncertain RIS). Serum magnesium was significantly lower in all diabetics, both before and during the test. There was no change during the OGTT-glucagon-test and no difference among the three groups of insulin-dependent diabetics. So, we conclude that a small RIS in our longterm insulin-dependent diabetics has no influence on the behaviour of serum magnesium. But, magnesium depletion can influence coronary blood flow, blood clotting, and atherogenesis. Therefore, it should be necessary to pay more attention to the hypomagnesemia in insulin-dependent diabetics.

Adult↗

The effect of potassium, calcium and magnesium concentration on insulin and glucagon secretion of the perfused dog pancreas.

The effect of different potassium, calcium and magnesium concentrations in the perfusate on the hormone secretion of the isolated dog pancreas was investigated. A potassium concentration above 15 mMol/l shortly stimulates the insulin and glucagon secretion. Potassium ions (greater than or equal to 15 mMol/l) completely inhibit the early phase of glucose-induced insulin release. At a low Ca2+-level (0.25 mMol/l) the glucose-stimulated insulin secretion is reduced to basal values. On the other hand, the glucagon release is stimulated under these conditions. An increase of magnesium ions from 1.0 mMol/l to 2.5-7.5 mMol/l strikingly inhibits insulin and glucagon release by approximately 50%, which is compensated for insulin by increasing the Ca2+-content of the medium. Perfusates for normothermic pancreas perfusion should contain electrolyte concentrations within the physiological range.

Animals↗

Measurement of plasma canine C-peptide by radioimmunoassay.

A sensitive radioimmunoassay (RIA) for canine C-peptide (CCP) was established using synthetic CCP, a specific antiserum, and rabbit anti-guinea pig serum. Radioiodination was performed according to a modified chloramine-T method. Tracer preparations were used for long as 6 weeks after iodination. The standard curve ranges from 0.028 to 3.0 nmol/l. The intra-assay coefficient of variation (CV) was 3-5% and the inter-assay CV was 6-9% in the optimal range between 0.3 and 0.8 nmol/l. The average recovery of CCP added to plasma samples was 100.6% (n = 9). Canine insulin, porcine proinsulin, bovine proinsulin, and human C-peptide exhibited no cross-reactivity. The mean fasting plasma CCP concentration was 0.089 +/- 0.021 nmol/l in normal dogs and -0.005 +/- 0.007 nmol/l (mean +/- SEM) in diabetic dogs, respectively.

Animals↗

The effects of subdiabetogenic streptozotocin doses on rat beta cell volume and functions.

The influence of a single i.v. injection of 30 mg/kg streptozotocin (SZ) into female Wistar rats on plasma glucose, pancreatic insulin content, volume and function of the remaining beta-cells has been investigated. 14 days after SZ treatment most animals remained normoglycemic; only about 15% showed permanent hyperglycemia. The pancreatic insulin content in normoglycemic rats was reduced to 30%, whereas in hyperglycemic rats only 6% of control values could be detected. The remaining beta-cell volume was comparable in the two groups, indicating no correlation between pancreatic insulin content and residual beta-cell volume. The glucose- and IBMX-stimulated insulin release of islets isolated from normoglycemic cats 14 days after SZ application was not significantly altered whereas the islets insulin content of SZ treated animals was significantly lowered in comparison to controls.

1-Methyl-3-isobutylxanthine↗

Effects of islet transplantation on the recipient endocrine pancreas.

Streptozotocin diabetic rats were treated with a syngeneic splenic islet transplantation. 17 weeks later the insulin content and the beta-cell mass were investigated in the host pancreas and compared with untreated diabetic or normal rats. The diabetic animals retained 8% of beta-cells, and 2.5% of insulin content as compared with normal controls. Successfully grafted rats are characterized by an increase of beta-cell volume (420%) and insulin content (2350%) in comparison to untreated diabetic rats. However, a detailed individual analysis revealed a marked differentiation between the animals investigated, the cause of which remains to be clarified.

Animals↗

Effect of islet cell surface antibodies on neonatal rat pancreatic islet cells or isolated islets of Langerhans in vitro.

Islet cell surface antibodies (ICSA) raised by immunizing rabbits with pancreatic islet cell suspensions were characterized with respect to some aspects of their influence on neonatal rat islet cells or isolated islets of Langerhans. The removal of unspecific cytotoxic factors by absorption with liver powder and spleen cells was reflected in changes of the antibody binding pattern to islet cells demonstrated by flow-cytometric analysis as well as the corresponding 51Cr-release from prelabelled islet cells. Using neonatal rat pancreatic islets as a target, fresh ICSA-positive serum provokes a beta-cell specific insulin leakage in a concentration dependent manner. In contrast to heat-inactivated antiserum the complement-mediated cytotoxic effect of rabbit anti-rat islet cell surface antiserum seems to have its morphological expression also in alterations of the islet surface structure as revealed by scanning electron microscopy.

Animals↗

Canine C-peptide for characterization of experimental diabetes in dogs.

Radioimmunoassay of canine C-peptide (CCP) was developed for the characterization of endogenous beta cell function in experimentally diabetic dogs. The animals were rendered diabetic by subtotal pancreatectomy and intrasurgical infusion of 2 mg kg-1 streptozotocin into the superior pancreaticoduodenal artery. After an average duration of diabetes of 5 months the animals showed zero peripheral venous fasting CCP levels with no response to feeding, OGTT/i.v. glucagon loading or i.v. glucose tolerance testing. The data on CCP levels were entirely coincident with simultaneously measured plasma IRI levels. In non-diabetic control animals there were clear-cut CCP increases after all stimuli. The experimental model provided an IDDM-type diabetes without toxic symptoms but with sufficient exocrine pancreatic function. The comparison showed that plasma IRI analyses would also allow a reliable characterization of insulinogenic functions in these animals.

Animals↗

The encapsulation of pancreatic islets. Investigation of insulin secretion and content in vitro.

Polyelectrolyte complex capsules from cellulose sulphate can be formed by precipitation in a polycation bath. The application of this new method for encapsulation of pancreatic islets requires investigations whether and to what extent cellulose sulphate injures viability and functionality of the pancreatic islets. Islets cultures in the presence of 2% cellulose sulphate for up to 3 weeks are characterized by unchanged insulin content, secretion and biosynthesis when compared to appropriate controls.

Animals↗

Tolbutamide does not alter insulin requirement in Type 1 (insulin-dependent) diabetes.

We examined whether tolbutamide has any acute or short-term effects on insulin action in Type 1 (insulin-dependent) diabetes. A euglycaemic glucose clamp was performed in seven Type 1 diabetic patients without clinical insulin resistance by infusing glucose at a constant rate of 0.01 mmol X kg-1 X min-1 for 3h together with a simultaneous insulin infusion using an 'artificial pancreas'. The insulin infusion rate required to maintain blood glucose at 6.7 mmol/l at a set low glucose infusion rate provides an index of insulin action in vivo. The euglycaemic clamp was performed on 3 separate days in the same patient: (1) in the basal state; (2) during simultaneous intravenous tolbutamide infusion of 0.5 g/h, and (3) after treatment with 2.5 g tolbutamide/day for 6 days in addition to insulin. The insulin infusion rate needed to maintain the set blood glucose level did not differ significantly between the three experimental conditions (1.2 +/- 0.2 versus 1.3 +/- 0.3 versus 1.2 +/- 0.3 U/h). Plasma glucagon, growth hormone, non-esterified fatty acid and glycerol levels did not differ between control or sulphonylurea treatment studies. The results suggest that tolbutamide does not exert any acute or short-term effects on insulin action in vivo in Type 1 diabetes. Our results do not provide support for the idea that this agent is a clinically useful adjunct to insulin in such patients.

Adult↗

The in vitro insulin secretion of human fetal pancreatic slices from diabetic and non-diabetic women--a methodical study.

The in vitro insulin secretion of pancreatic slices between the 11th and 15th week of pregnancy of fetuses from non diabetic ( FNDW ) and diabetic women ( FDW ) after incubation in media supplemented with different secretagogues was investigated in order to study the development of diabetic fetopathy during human pregnancy in diabetic women. There was a stimulatory effect on the insulin secretion in FNDW even if glucose alone was used, which became more pronounced if IBMX was added to the incubation medium. The insulin secretion was significantly enhanced in FDW compared to FNDW . This incubation model using fetal pancreatic slices seems to be appropriate for studying the ontogenesis of the human fetal pancreas.

Female↗

Short-term of the artificial beta-cell (Biostator) on pancreatic glucagon response in insulin-dependent diabetic (IDDM).

The short-term effect of the glucose-controlled insulin infusion system (GCIIS) Biostator on metabolic and hormonal responses to a 2 h glucose infusion (0.33 g/kg body weight glucose i.v. followed by an infusion of 12 mg/kg/min) was studied in 8 insulin-dependent diabetic patients (IDDM). Normalization of glucose tolerance by means of GCIIS was associated with significant improvement of lipid metabolism in IDDM. Endogenous insulin secretion (C-peptide) was not altered significantly under the experimental conditions. The results demonstrate that immunoreactive glucagon response to intravenous glucose infusion was restored by treatment with GCIIS in IDDM irrespective of no prolonged duration of normoglycemia. The results provide further support that abnormal glucagon response in some IDDM is secondary to insulin deficiency.

Adult↗

Relationship between insulin secretion and pancreas morphology in subjects with chronic pancreatitis.

In order to investigate whether a relationship exists between in vivo insulin secretion and islet mass, 8 patients suffering from severe chronic relapsing pancreatitis were studied before and after pancreatectomy by glucose-glucagon-test (per os 1.75 g glucose; i.v. glucagon 0.01 mg/kg b.w.) and by intravenous glucose-tolerance-test (iGTT) (i.v. glucose 0.33 g/kg b.w.). Postoperative in vitro assessments of pancreatic insulin and alpha-amylase content were performed, and morphometric studies were carried out. Patients were characterized by reduced c-peptide secretion when compared with healthy subjects. The c-peptide response to the glucose-glucagon-test correlated well with the morphometrically estimated exocrine and islet tissue mass (P less than 0.05) and with the content of insulin and amylase in the tissue. The findings suggest that in subjects suffering from severe chronic relapsing pancreatitis the maximal insulin response might represent a parameter for the patient's islet mass.

Adult↗

[Effect, on the newborn infant, of carbohydrate metabolism in pregnancy in insulin-dependent diabetics].

The influence of the moment in pregnancy of insulin dependent diabetic women, at which normoglycemia by insulin therapy could be reached, on cord blood insulin concentration and neonatal morbidity was investigated. There is a positive correlation between the moment of normoglycemia (HbA1-values less than or equal to 8.5%) and the insulin concentration and furthermore the incidence of respiratory distress syndrome and macrosomia in the newborn. It is concluded that a tight metabolic control in insulin dependent diabetic women already prior to or early in pregnancy (at least until the 16th week) will be able to decrease the incidence of morbidity in infants of diabetic mothers.

Adult↗

Absorption rates of subcutaneously injected insulin in the dog as calculated from the plasma insulin levels by means of a simple mathematical model.

The appearance rate of insulin (calculated insulin secretion rate) in the circulating blood after subcutaneous injection was estimated in diabetic dogs from serial measurements of immunoreactive insulin concentrations using a simple mathematical model based on the insulin half-life and the distribution space. In the case of highly purified monocomponent porcine insulin, maximum concentrations occurred after 30-60 min. The duration of insulin appearance was dose-dependent and the rate of appearance could be described by a bi-exponential function. It was linearly dose-dependent but the effect on glycaemia showed saturation kinetics. The action of the injected dose on the fasting glycaemia diminished when the appearance rate became less than 0.3 mU X kg-1 X min-1. Fractional dose recovery was between 70% and 90% and was not different between depot and regular insulin. Appearance kinetics were not significantly affected by the initial glycaemia. The model presented provides a means for quantitative characterization of different insulin preparations.

Absorption↗

Enhanced synthesis, storage, and secretion of insulin in pancreatic islets derived from obese subjects.

Insulin biosynthesis, content, and secretion were investigated in islets derived from pancreas specimens of normal weight (100.4 +/- 1.1% of ideal body weight) and obese (137.2 +/- 5.9% of ideal weight) patients. The pancreatic islets from the obese subjects were characterized by a significantly enhanced glucose-induced insulin secretion and biosynthesis and by an insulin content that was nearly double when compared with islets from the nonobese subjects. The results support the hypothesis that an enhanced beta-cell reactivity significantly contributes to the insulin hyperresponse observed in the obese state.

Adult↗

Characterization of pseudo-islets formed from pancreatic islet cell suspensions of neonatal rats.

Well-preserved pancreatic islet cell suspensions were prepared from islets of Langerhans of neonatal rats by gentle trypsin treatment. Within a culture period of 4-6 days the islet cells reaggregate spontaneously and form pseudo-islets of different size and of a variable insulin content. While the ratio of insulin to glucagon in isolated islets of Langerhans is constant (18 +/- 1.9), the hormone ratio of the pseudo-islets is strongly variable and increased, indicating an excess of insulin. Glucose enhancement from 1.5 mmoles/l to 15 mmoles/l results in a significant stimulation of (pro)insulin biosynthesis whereas insulin secretion of the pseudo-islets is only slightly increased. At high glucose concentration (15 mmoles/l) insulin secretion of the pseudo-islets can be potentiated (by a factor of 4.5 +/- 0.46) by 3-isobutyl-l-methylxanthine (IBMX). Compared with the initial islet cell suspension, the cell aggregation during pseudo-islet formation did not result in an enhanced secretory response on glucose stimulation.

Animals↗