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Biomedical subjects

H Jahr

Publications and source records attributed to H Jahr.

At least 73 records · Page 4Linked to original sources

Secretion and biosynthesis of (pro)insulin by pancreatic islets isolated from fetuses of normal and diabetic women.

Insulin secretion, biosynthesis and content of isolated pancreatic islets prepared for fetuses of nondiabetic or insulin-dependent diabetic women were investigated in vitro. Glucose failed to stimulate the hormone release during an incubation period of 60 min in islets of fetuses from non-diabetic women. Prolongation of the glucose exposure or the addition of theophylline resulted in a significantly enhanced insulin release. The islets isolated from fetuses of insulin-dependent mothers are glucose-sensitive with respect to hormone release and biosynthesis. The results demonstrated that the human fetal B-cell is glucose-sensitive after glucose exposure. The differences between the islets of fetuses of nondiabetic and diabetic women are discussed as a response to the fetal plasma glucose levels.

Diabetes Mellitus↗

Insulin secretin of rat pancreatic islets incubated with autologous or heterologous serum.

Isolated rat pancreatic islets were incubated with either rat or human serum. Undiluted serum of both rat and man provided a strong insulin release, probably caused by a leakage of damaged B-cells. Heat inactivation of the serum only partially reversed this effect. Serum, which was diluted by 50% with buffer, had a much smaller cytotoxic activity. The effect on insulin leakage was further depressed when the complement system of the serum was inactivated by heat or zymosan treatment or storage of the serum before use. When rat islets were incubated in rat or human serum pretreated in this way, the glucose effect on insulin secretion could be determined.

Animals↗

[Follow-up examination of neurotic patients after dynamic group therapy with the FPI and a change questionnaire].

On the basis of the FPI and a questionnaire about the occurrence of changes the therapeutic effects of a dynamic group psychotherapy were checked. 63.6 per cent of the patient showed positive results in the FPI after four months. In some checkups (13 months after the end of the therapy) 40 per cent of these FPI patients also showed positive social changes while in 23.3 per cent no or negative changes in the social sphere were found. The 36.7 per cent FPI-negative patients fall into 16.7 per cent socially positive and 20 per cent unchanged or negative patients. The study shows that there is no verified agreement between the results of FPI and the behaviour in the social sphere.

Adult↗

Insulin secretion in maturity-onset-diabetes. Function of isolated islets.

An impaired insulin response to glucose is a characteristic finding in maturity onset diabetes (MOD). To clarify whether the decreased insulin response in vivo is related to a primary defect of the beta-cells, isolated islets of MOD - obtained by intraoperative biopsy - were examined for their insulin content, biosynthesis and release. The in vitro experiments showed that despite a missing or significantly reduced insulin response in vivo the isolated beta-cells of the same patients had a normal insulin content, a normal or even high biosynthesis, and insulin release could be induced by glucose. These results suggest that the primary defect in MoD cannot be related to an intrinsic failure of the beta-cells to response to glucose; extrapancreatic factors seem to influence their reaction to glucose. These factors may be of a higher level in those patients or the reaction of the beta-cells is more inhibited by the same concentrations in diabetic patients.

Aged↗

Transcriptional and translational control of glucose-stimulated (pro)insulin biosynthesis.

Islets of Langerhans were isolated from the pancreata of fed or 48-h-fasted Wistar rats. The islets were incubated with either [3H]leucine of [3H]uridine. Inhibition of RNA synthesis by actinomycin D or by alpha-amanitin for 4 h had no influence on the (pro)insulin biosynthesis of isolated islets of fed rats. The (pro)insulin biosynthesis was not inhibited after two days incubation of islets of fed rats with alpha-amanitin either. Incorporation of labelled uridine into total RNA for 3 h was stimulated by glucose in islets of fasted, but not of fed rats. Therefore, it was concluded that transcriptional control does not participate, even for longer periods than believed previously, in acute regulation of (pro)insulin biosynthesis of islets isolated fed rats. Despite the strong and preferential stimulation of (pro)insulin biosynthesis of islets of fed rats by glucose the radioactivity of the [3H]uridine-labelled polysomes active in proinsulin synthesis remained unchanged. To interprete these experimental data we suggest that glucose triggers the transformation of a translationally inactive form of pre-proinsulin mRNA to a translationally active form.

Amanitins↗

Changes in glucose-stimulated insulin secretion after long-term treatment of C57BL mice with glibenclamide.

An insulin response to increased glucose concentrations could not be found in vivo and in vitro after long-term treatment of C57BL/KsJ and C57BL/6J mice with Glibenclamide. This missing stimulation of insulin secretion was not the result of an exhaustion of the islets or a disturbed (pro)insulin biosynthesis as demonstrated by measurements of insulin content of the islets and by in vitro (pro)insulin biosynthesis experiments. In the presence of glucose (15 mmol/l) theophylline increased the insulin secretion of isolated islets of Glibenclamide-treated mice to values similar to control islets. The insulin response to an i.p. glucose loading was found to be normal in comparison with control mice 1-2 weeks after the Glibenclamide treatment had been finished.

Animals↗

Influence of pilocarpine pretreatment on (pro)insulin biosynthesis of isolated islets of rats.

3[H]-Leucine incorporation into (pro)insulin and insulin secretion was investigated using islets prepared by collagenase digestion from pancreata of rats pretreated with the cholimimetic agent pilocarpine or with saline (controls). Under the influence of pilocarpine pretreatment the [3H]-leucine incorporation into islet proteins with insulin immunoreactivity is enhanced at 6 mM glucose in the incubation medium of the islets but the incorporated radioactivity at 18 mM glucose is independent of the pretreatment of the animals. Only small or no changes were found regarding insulin secretion. It is concluded that an influence of pilocarpine pretreatment should be taken into consideration using such islets for studies on the regulation of (pro)insulin biosynthesis.

Animals↗

Biosynthesis of somatostatin in pancreatic islets of Wistar rats.

Pancreatic islets of Wistar rats were isolated by collagenase digestion and incubated with [3H]-L-phenylalanine. Using a specific somatostatin antiserum radioactivity was found in the antibody-antigen-complex. The radioactivity was displaced by unlabelled somatostatin. These findings give the first evidence for the biosynthesis of somatostatin or somatostatin-like peptides in mammalian pancreatic islets.

Animals↗

Studies on the (pro) insulin biosynthesis of islets of Langerhans of sand rats (Psammomys obesus).

By feeding a regular laboratory chow, sand rats (Psammomys obesus) from our breeding colony gained different body weights, though they received approximately the same quantity of calories. Sand rats, reaching a body weight above 160 g (group B) showed significantly increased blood glucose values in contrast to the animals with a body weight under 160 g (group A). Isolated pancreatic islets of these two groups of sand rats were incubated with [3H]-leucine to study the incorporation of this amino acid into proinsulin and insulin. The incorporation into proteins of pancreatic islets of sand rats of group B was stimulated by 0.45 mg and 3.0 mg/ml glucose. In group A there was no further stimulation from 0.45 mg to 3.0 mg/ml glucose. Insulin secretion could be stimulated by glucose in both groups, but the stimulation was stronger in group B than in group A.

Animals↗

Proteolytic and transhydrogenolytic activities in isolated pancreatic islets of rats.

In homogenates and subcellular fractions of pancreatic islets of Wistar rats we could demonstrate three groups of protein degrading enzymes. The proteinases of group 1 are characterized by both trypsin-like and carboxypeptidase B-like specificities with slightly acid pH optima (pH 5.5-6.5) and seem to play important roles in the conversion of proinsulin into insulin. The properties suggest that these enzymes localized in the secretion granule/mitochondria fraction are related to the tissue cathepsins. Group 2 enzymes are thiol-depending proteinases with a pH optimum at 7.0 occuring mainly in the cytosol and to a lesser extent in the fraction of nuclei and cell debris. Group 3 represents the thiol protein oxidoreductase with a pH optimum of 7.0. This enzyme degrading disulfide bonds could also be important in the formation of the disulfide bonds during protein folding after synthesis.

Animals↗

Demonstration of insulin degradation by thiol-protein disulfide oxidoreductase (glutathione-insulin transhydrogenase) and proteinases of pancreatic islets.

Homogenate preparations of pancreatic islets have been found to degrade insulin by cleavage of the interchain disulfide bonds, followed by proteolysis of the resulting A and B chains. A proteolytic system of the pancreatic islets splitting not only 125I-labeled insulin A chain but also 125I-labeled glucagon at pH 7.0, was shown to be activated by glutathione and inhibited by EDTA. The results suggest that pancreatic islets contain both the thiol-protein disulfide oxidoreductase (glutathione : protein-disulfide oxidoreductase, EC 1.8.4.2) and the A and B chain-degrading enzyme(s). The effects of EDTA argue against the implication of cathepsins in insulin breakdown under the experimental conditions employed.

Amylases↗

Investigations on isolated islets of Langerhans in vitro. XIII. Experiments concerning the preparation conditions with collagenase.

During the digestion of pancreatic pieces with collagenase for prepartion of isolated islets the enzymes in incubation medium (collangenolytic and/or proteolytic) can alter the secretion behavior of A- and B-cells. Insulin release after such an enzymatic attack is characterized by an enhanced basal secretion and a diminished and delayed glucose response. Overdigestion results in a decreased glucagon secretion in response to arginine, a diminished insulin content, and a decreased thiol-protein-disulfide-oxidoreductase activity of the islets. Increased albumin concentrations did not prevent the collagenase effect.

Animals↗

Oxidoreductases and hydrolases as marker enzymes for ultracentrifugation of islets of Langerhans of rats.

Using quantitative fluorometric micro methods the presence of glutamate dehydrogenase, acid galactosidase, and acid glucuronidase was detected in pancreatic islets of the rat. Some properties of these enzymes and of malate dehydrogenase, 6-phosphogluconate dehydrogenase, and acid phosphatase were investigated. It has been shown that subcellular fractions of homogenates of islets of Langerhans can be characterized by using glutamate dehydrogenase, 6-phosphogluconate dehydrogenase, and acid hydrolases as marker enzymes for mitochondria, cytosol, and lysosomes, respectively. The degree of contamination from acinar tissue in the islet preparations was calculated from the amylase activity of the homogenates.

Acid Phosphatase↗

[(Pro)insulin biosynthesis of isolated islands of Langerhans in the sand rat and Wistar rat].

Sand rats develop a diabetes-like syndrome, connected with temporary hyperinsulinism, when fed a rat laboratory chow diet. The conversion of proinsulin to insulin is not disturbed in these animals. Sand rat islets do not secrete newly synthesized (pro) insulin preferentially. Time course and glucose response of [3H]-leucine incorporation are different between islets of sand rats and Wistar rats.

Animals↗

Investigations on isolated islets of Langerhans in vitro. Influence of temperature changes during preparation on some parameters of insulin metabolism.

Pancreatic islets of Wistar rats were prepared by digestion with collagenase and then washed and isolated at three different temperatures (4, 22 and 37 degrees C). The efficiency of washing with regard to proteolytic and collagenolytic activities in the wash buffer was not affected by the temperatures used. The islet thiol:protein-disulphide oxidoreductase activity (EC 1.8.4.2) was apparently unchanged, whereas washing temperatures lower than 37 degrees C resulted in a diminished insulin content. The insulin secretion of islets, isolated at 4 degrees C, is reduced in response to glucose without changing the sigmoidal shape of dose-response curve.

Animals↗