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H J Hahn

Publications and source records attributed to H J Hahn.

At least 181 records · Page 10Linked to original sources

[Results of islet transplantation in diabetic dogs].

The influence of histocompatibility on islet transplantation in dogs was studied. Donors and hosts were chosen by help of the macrophage-electrophoresis-mobility test. By subtotal pancreatectomy and twice applying streptocotocin diabetes was successfully induced in recipient animals. Isolation of pancreating islets from the donor was done by means of the collagenase method combined with the Ficoll-gradient-separating technique. The grafting occurred via portal vein into the liver. Significant decrease of blood sugar during 10 weeks was observed in animals with good compatibility. This effect lasted only 14 days in cases of bad compatibility. Concentrations of insulin in the portal vein and superior caval vein 4 weeks after grafting was lower in cases with high-grade histoincompatibility. The duration of functioning of transplanted islets depends on the histocompatibility.

Animals↗

Investigations on isolated islets of langerhans in vitro. 16.Modification of the glucose-dependent inhibition of glucagon secretion.

Investigation of glucagon secretion in isolated Wistar rat islets was carried out to elucidate further the regulatory function of glucose and arginine on pancreatic A-cells. The suppressive effect of D-glucose could also be demonstrated with L-glucose, D-mannose, D-fructose, D-galactose, D-glyceraldehyde and DL-dihydroxyacetone, but not in the presence of 3-O-methylglucose or mannitol. Sugars other than D-glucose inhibited glucagon secretion only at much higher concentrations than those at which D-glucose was effective. Furthermore, although 7.5 mM D-glucose up to 80% inhibition, the effects of other sugars appeared to level off at only 50--60% inhibition. The inhibitory action of D-glucose or D-glyceraldedyde on glucagon secretion could not be overcome by L-arginine, but 3-O-methylglucose, mannoheptulose, 2-deoxy-D-glucose, iodoacetamide, theophylline, epinephrine and acetylcholine were effective. The insulin secretion in response to glucose was inhibited by the metabolic inhibitors used, whereas the B-cell response in the presence of glyceraldehyde was diminished by iodoacetamide only. Like D-glucose, a variety of other sugars markedly reduced the stimulatory effect of L-arginine in glucagon release. The results show that the suppression of glucagon secretion is not specific for D-glucose and not strongly connected on a stimulated insulin secretion.

Acetylcholine↗

[Obesity as a metabolic risk factor].

On the basis of the results of clinico-experimental examinations and of animal experiments the importance of obesity as metabolic factor of risk is confirmed and hereby the diabetes mellitus as well as cardiovascular effects are particularly taken into consideration. Conclusions are made relevant to practice and it is particularly referred to the central position of the B-cells for the pathogenesis of diabetes as well as to prophylactic and early therapeutic measures.

Adult↗

A-cell behavior in organ culture of isolated rat islets: secretion and tissue content of glucagon and insulin.

The present study was done to characterize the hormone secretion and content of isolated rat islets in organ culture dependent on the glucose concentration and the number of cultivated islets per culture bottle (10 or 30). For the calculation of the recovery rate the glucagon and insulin breakdown in the culture medium containing 10% calf serum was assayed. The glucagon recovery after incubation for 24 h at 37 degrees C varied from 2 to 92% and that of insulin from 75--105% depending on the serum batches. The cultivated islet responded to 16 mmol glucose by a significant enhancement of insulin release, whereas the glucagon release was not influenced. The glucagon release fell progressively with the duration of cultivation. 2 mmol dibutyryl cyclic AMP augmented insulin and glucagon release in the presence of 5 and 16 mmol glucose and significantly enhanced the glucagon content in the cultivated islets.

Animals↗

Successful cultivation of isolated islets of Langerhans without attachment: relationship between Glucose- and theophylline-induced insulin release and insulin content in rats islets after cultivation.

The effect of various inhibitors of insulin secretion such as mannoheptulose (20 mM), atropine (1 mM), diphenylhydantoin (20 microng/ml), high concentration of Mg++ (5.3 mM) in the presence of 20 mM glucose (control) on insulin content and secretion from collagenase-isolated rat pancreatic islets was studied in vitro by cultivation of islets up to 5 or 9 days in glass Petri dishes without attachment. In a following short-term incubation for 60 min the glucose-induced insulin release without and with theophylline (5 mM) was investigated. Islets cultivated at 5 mM glucose and at 20 mM glucose with the inhibitors mannoheptulose or atropine lost the responsiveness to glucose and theophylline whereas such islets cultivated at 20 mM glucose alone or with diphenylhydantoin (DPH) or 5.3 mg Mg++ showed a stimulation of insulin secretion by glucose and theophylline. Compared, however, with freshly isolated islets all cultivated islets were restricted in their maximal glucose response and this defect was not evoked alone by quantitative changes in islet insulin content. Nevertheless, culture conditions which facilitate a net increase of insulin (content and release) during cultivation influenced also positively the glucose-induced insulin release without and with 5 mM theophylline in the following short-term experiments.

Animals↗

Insulin and glucagon secretion and the insulin sensitivity of peripheric organs of colony-bred sand rats fed with pellet diet after weaning.

Colony-bred sand rats were fed with rat pellet chow in restricted quantities or ad libitum for 8--10 or 28--31 weeks after weaning. The changes of glucose metabolism were characterized by an intraperitoneal glucose tolerance test. The daily food intake and the average weight gain differed only in the first 5--7 weeks of pellet nutrition. In the impaired glucose tolerance tests of all sand rats the high basal plasma IRI levels were not significantly increased by the grossly enhanced blood glucose concentrations. The insulin secretion of either acutely incubated or for 8 days cultivated isolated pancreatic islets, however, was stimulated already by low (1.7 and 5 mM) glucose concentrations in all diet groups. Otherwise the glucagon secretion of isolated islets was not suppressed by high glucose concentrations. No changes of insulin or glucagon contents of islets were found in the different diet groups. The adipocytes of all animals revealed a complete ineffectiveness of insulin on the glucose utilization to CO2 and triglycerides. The basal glucose conversion to CO2 and glycogen in skeletal muscle and the stimulatory potency of insulin was low and not distinctly different in all groups. In liver glycogen and triglyceride contents as well as gluconeogenic enzyme activities were not influenced by feeding of different quantities of pellet diet at the investigated time points. The time course of the metabolic and clinical alterations demonstrates that the peripheral organs become insensitive to insulin in the first weeks after weaning.

Animals↗

Insulin secretion reactivation of pancreatic islets from starved rats in vitro.

Starvation of Wistar rats induced a shift of glucose threshold for insulin secretion of isolated islets above 5 mM, which can be restored by pretreatment of the tissue with glucose, mannose, glyceraldehyde, an theophylline, but not with acetylcholine or lactate. The improved insulin secretion is not connected with an enhanced glucose utilization.

Animals↗

[Regulation of pancreatic glucagon secretion].

Intensive investigations during the last few years have shown that the regulation of the secretion of pancreatic glucagon is controlled by nerval, humoral and metabolic factors. Of decisive importance is the actually present glucose level which by inhibition modifies the effectiveness of the most different stimulators (intestinal hormones, amino acids). In addition to this the hormones insulin and somatostatin formed by the islets of Langerhans of the pancreas seem to be of importance for the local reactivity of the A-cells of the endocrine pancreas. Disturbances of the glucagon secretion of the pancreas have been found in different diseases connected with hyperglycaemia (especially in diabetes mellitus). The review tried to summarize our present knowledge of the physiology and pathophysiology in this field.

Amino Acids↗

Role of mannosyl lipid intermediate in the synthesis of Neurospora crassa glycoproteins.

Particulate membrane preparations from Neurospora crassa incorporated mannose from GDP-[14C] mannose into endogenous lipid and particulate protein acceptors. Synthesis of the mannosyl lipid is reversible in the presence of GDP. Chemical and chromatographic characterization of the mannosyl lipid suggest that it is a mannosylphosphorylpolyisoprenol. The other endogenous acceptor was precipitated by trichloracetic acid. Gel filtration and electrophoresis studies before and after treatment with proteolytic enzymes indicate that the second acceptor is a glycoprotein(s). beta Elimination studies on the mannosyl protein formed from GDP-[14C] mannose with Mg2+ in the reaction mixture or formed from mannosyl lipid indicate thad with the peptide chain. Several lines of evidence indicate that in Neurospora crassa the mannosyl lipid is an obligatory intermediate in the in vitro mannosylation of the protein. (a) At 15 degrees C the initial formation of the mannosyl lipid is faster than the initial formation of the mannosyl protein. (b) Exogenous partially purified mannosyl lipid can function as a mannosyl donor for the synthesis of the mannosyl protein. This reaction was also dependent on a divalent metal. The rate of this reaction was optimal at a concentration of Triton X-100 which effectively inhibited the transfer of mannose from GDP-[14C] mannose to lipid and protein, indicating that GDP-mannose was not an intermediate in the transfer of mannose from lipid to protein. The mannosyl protein formed in this reaction was indistinguishable by several criteria from the mannosyl protein formed from GDP-[14C] mannose and Mg2+. (c) The effect of a chase with an excess of unlabeled GDP-mannose on the incorporation of mannose into endogenous acceptors was immediate cessation of the synthesis and subsequent turnover of the mannosyl lipid; in contrast, however, incorporation of mannose into protein continued and was proportional to the loss of mannose from the mannosyl lipid.

Glycolipids↗

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↗

Insulin and glucagon secretion by pancreatic islets from nondiabetic and diabetic sand rats (Psammomys obesus).

The secretion of insulin and glucagon was investigated in pancreatic islets from diabetic and nondiabetic sand rats of similar age and weight. The metabolic characterization was based on an intraperitoneal glucose tolerance test. Compared to nondiabetic animals diabetic sand rats had a diminished insulin content in their islets and a decreased insulin secretory response to glucose, glyceraldehyde and theophylline. Diazoxide inhibited insulin release in diabetic as well as in nondiabetic sand rats whereas mannoheptulose was effective only in the nondiabetic rats. There was no significant difference in glucagon content between the two groups. The glucagon secretion by pancreatic islets of diabetic animals was not suppressed by glucose, as in nondiabetic sand rats islets, but by glyceraldehyde. This indicates that the sensitivity to glucose rather than the suppressibility of glucagon release was altered.

Animals↗

Enhancement of glucose-stimulated insulin secretion from isolated rat pancreatic islets by human insulin antibodies.

Isolated pancreatic rat islets incubated in vitro were used as a bioassay system for investigating the influence of human insulin antibodies on insulin secretion. Serum samples with different titres of insulin antibodies were obtained from juvenile diabetics after various periods of insulin therapy. The insulin secretion of isolated islets is enhanced by insulin antibodies and positively correlated to the measured antibody titres in serum.

Adult↗

Somatostatin-induced inhibition of insulin secretion by isolated pancreatic rat islets prepared by micro-dissection or collagenase digestion.

The effect of somatostatin on insulin secretion in response to a variety of stimuli was investigated in micro-dissected as well as collagenase isolated pancreatic rat islets. Somatostatin inhibited insulin secretion in both islet preparations in the presence of different initiators, but failed to affect the hormone output induced by theophylline, 1-methyl-3-isobutylxanthin (IBMX) or p-chloromercuriphenylsulfonic acid (CMBS). The inhibitory action was associated with decreased glucose metabolism by islets (measured as conversion of U-14C-glucose to 14CO2).

Animals↗