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Biomedical subjects

B Ziegler

Publications and source records attributed to B Ziegler.

At least 127 records · Page 7Linked to original sources

[Somatostatin. I: Structure, biosynthesis and effect].

Somatostatin is synthetized and stored in the D-cells of pancreatic islets. It seems to inhibit immediately the secretion of insulin and glucagon which are synthesized in the B- and A-cells, respectively. For better understanding of these processes problems of cell differentiation of the pancreas as well as the mechanism of action of somatostatin are discussed. By means of analogues of somatostatin the half-life time and selectivity of the action can be increased obtaining a better possibility for clinical use.

Cell Differentiation↗

Reversal of diabetes by isogeneic transplantation of cultured pancreatic islets.

Pancreatic islets were isolated by collagenase digestion from female Wistar rats and cultured at 20 mmol/l glucose. The enhancement of Mg++ concentration from 0.8 mmol/l up to 5.3 mmol/l had a protecting effect on the glucose-induced insulin release in the subsequent short-time incubation and prevented the age-depending decrease of B-cell function. About 1,000 cultured islets injected into portal vein normalized the plasma glucose of streptozotocin-diabetic rats. The plasma glucose patterns during the glucose load were nearly identical to healthy controls. These findings suggest that the cultured islets maintain the ability to secrete insulin in response to glucose in vitro as well as in vitro and that such islets can reverse an experimentally induced diabetes.

Animals↗

[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↗

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↗

Influence of culture conditions on B-cell functions in vitro.

Isolated pancreatic islets from Wistar rats were maintained in vitro at 37 degrees C for 12 days in TCM 199 containing 10 mmol/l glucose and supplemented with 10% serum. 10 mmol/l glucose completely prevented the diminution of insulin content independent of the type of serum (fetal calf serum; serum from newborn calfs; horse serum), whereas the insulin biosynthesis as well as the insulin release were modulated by the kind of serum. Fetal calf serum can be replaced by horse serum.

Animals↗

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↗

The influence of cultivation on (pro-)insulin biosynthesis and secretion of isolated pancreatic islets of C57BL-mice, long-term treated with glibenclamide in vivo.

Long-term treatment of C57Bl/KsJ and C57Bl/6J mice with glibenclamide in vivo caused a diminished response of insulin to high glucose concentrations (20 mmol/l). Islets of those mice were investigated to answer the question whether it is possible to overcome this diminution of glucose sensitivity by cultivation in presence of high glucose (20 mmol/l). The insulin release of islets of glibenclamide treated mice was significantly lowered also in the first 48 h of cultivation. In the following short-term incubation (2 h) no differences in the glucose stimulated insulin secretion could be seen. The second cultivation period (48-96 h) confirmed these results. Both groups of islets (controls and glibenclamide treated) reached comparable values in insulin release. Cultivation of islets of glibenclamide treated mice in presence of 20 mmol/l glucose for at least 2 days led to a restoration of the glucose sensitivity of insulin release. Insulin biosynthesis, judged by measuring 3H-leucine incorporation into (pro-)insulin, was largely unaffected. In all experimental conditions the insulin content was comparable to that of controls.

Animals↗

[Relationship between vitamin status (A, B1, B2, B6, and C), clinical features and nutritional habits in a population of old people (author's transl)].

112 patients in a medical ward were examined clinically and biochemically with regard to their vitamin status (plasma vitamin A, plasma vitamin C, blood glutathione reductase, vitamin B1, vitamin B2, N-methyl nicotinic acid amide and pyridoxic acid excretion). The nutritional habits were assessed by means of a questionnaire. The results of these two examinations were correlated with the clinical findings. The assessment of the vitamin B2 status showed a deficiency in 8 cases and a marginal vitamin B2 supply in a further 4 cases. The thiamine intake was insufficient in 43 cases and marginal in 42 cases. The biochemical assessment of vitamins C, B1 and PP indicated a deficiency of these vitamins. Dermatological signs pointed to a deficiency of vitamins A and B2. There was a significant correlation between the plasma vitamin A level and the serum iron level. The importance of milk and vegetables in the diet is stressed and also the association between milk consumption and the serum cholesterol level.

Aged↗

Effects of sulphydryl reagents on pancreatic glucagon secretion in vitro.

The effect of sulphydryl reagents on glucagon secretion of isolated Wistar rats islets was studied. Chloromercuribenzene-p-sulphonic acid (CMBS) is a strong stimulator of glucagon secretion, whereas 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) markedly inhibited the hormone release. The effect of CMBS could not be suppressed by 20 mM glucose, but in the presence of 1 mM 4-acetamido-4'-isothiocyano-stilbene-2,2'-disulphonic acid (SITS), and is independent of the glucagon content of islets. The results let us assume that sulphydryl-groups of pancreatic A-cells are involved in the regulation of glucagon secretion.

4-Chloromercuribenzenesulfonate↗

[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↗

[Sleep EEG alterations in patients suffering from circulatory disturbances. Relation to neurological and psychopathological changes (author's transl)].

In 30 conscious patients (24 men, 6 women) aged 30-74 years suffering from ischemic lesions in the cerebral hemispheres, polygraphic night sleep recordings were performed about 45 days after the beginning of the illness. The alterations in sleep were characterized by a delay in the onset of sleep, prolonged waking periods, and a reduction of deep synchronous sleep. Statistical analysis revealed a relationship between prolonged waking time with higher age as well as with high complex reaction time and euphoric state of mind, which can be considered as a sign of psycho-organic impairment. In contrast thereto, the degree of the neurological symptomatology is of less importance for the kind and extent of the sleep disturbances.

Adult↗

Gamma-aminobutyric acid (GABA) and sleep. The influence of di-n-propylacetic acid on sleep in man.

The effects of di-n-propylacetic acid (DPA) on sleep, for some years used as an anticonvulsive drug, has been investigated in 11 healthy volunteers using all-night sleep EEG recordings. DPA acts by an enhancement of the gamma-aminobutyric acid (GABA) level of the brain. Its influence on sleep seemed to be of interest on account of the metabolic relationship of GABA to other short chain fatty acids. After short-term application only a shortening of the time to fall asleep and of the waking time could be found, whereas under long-term administration a decrease in deep synchronous sleep could be observed. In contrast to the results known from animal studies no marked influence on REM sleep was observed. The action of DPA on sleep is similar to that of diphenylhydantoin. No so-called matitudinal 'hangover' could be revelaed in either drug;

Adult↗