Transport of -aminoisobutyric acid in mammalian pancretic -cells.
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Biomedical subjects
Publications and source records attributed to J Sehlin.
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The oxidation of alanine, arginine, leucine, glucose, and pyruvate was studied in microdissected pancreatic islets of obese-hyperglycaemic mice. The following main observations were made. The oxidation of glucose was enhanced severalfold when its concentration was raised from 3 to 20mm. At the latter concentration the rate was about 65mmol/h per kg dry wt. The oxidation of 17mm-pyruvate amounted to 20mmol/h per kg dry wt. indicating a significant entry of this compound into the beta-cells. Leucine oxidation was little affected by concentration changes above 5mm, the rate at 20mm corresponding to about 25% of that obtained with 20mm-glucose. In the absence of glucose, the oxidation of alanine or arginine was barely significant. Glucose stimulated the oxidation of alanine but depressed that of leucine. These effects of glucose were blocked by mannoheptulose or iodoacetamide but were not influenced by adrenaline, diazoxide, dibutyryl 3':5'-cyclic AMP, or glibenclamide. The rate of alanine oxidation was doubled in the presence of 17mm-pyruvate but was unaffected by citrate or succinate. Succinate depressed the oxidation of leucine. Neither alanine nor leucine significantly affected the oxidation of glucose. It is suggested that the effects of glucose on the oxidation of alanine and leucine were mediated by metabolism of the sugar, and that amino acids do not act as insulin secretagogues by serving as fuels for the beta-cells. The results are consistent with the existence of mechanisms auxiliary to glucose metabolism for control of insulin release.
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The fate of exogenous high-molecular-weight hyaluronic acid applied in the middle ear was studied in rats. Tritium-labelled hyaluronic acid was deposited, and its disappearance through the eustachian tube was followed by analysis of nasopharyngeal secretions. Radioactivity in the secretions reached a peak after three hours and approached zero after 12 hours, indicating that almost all hyaluronic acid had been removed. The middle ears were all empty when opened 24 hours after the deposition of hyaluronic acid. The fate of hyaluronic acid after obstruction of the eustachian tube was followed both with radioactive hyaluronic acid and subsequent autoradiography and by direct analysis of the hyaluronic acid concentration and the hyaluronic acid molecular weight distribution. Radioactive hyaluronic acid was confined to the obstructed middle ear, and no uptake into surrounding tissues could be detected between three hours and four days after the deposition. The amount of hyaluronic acid deposited could be recovered to about the same extent for up to six days. Analysis of the molecular weight distribution of the deposited material indicated only a slow degradation, if any, during the same time period.
The effects of furosemide on fasting serum glucose, glucose tolerance and pancreatic islet morphology were studied in ob/ob mice of two age groups, 3 months and 8 months. A single dose of furosemide (200 mg/kg body weight) induced acute hyperglycaemia in the young (3 months) as well as the old (8 months) ob/ob mice. Two days after the furosemide injection the glucose tolerance was markedly impaired in older animals, whereas it was normal in younger animals. Glucose tolerance in old mice varied markedly between individuals and showed two patterns. Thus, in one group of 8 months old mice, fasting serum glucose was elevated and glucose tolerance was very poor, whereas in the other group it was at least as good as in the saline-injected controls. Histological analysis showed normal islet morphology in furosemide-treatment young mice but an inflammatory reaction in islets from furosemide-injected old animals. A significant correlation between the degree of islet abnormality and glucose tolerance was observed. The data suggest that susceptibility to develop furosemide-induced long-term glucose intolerance is associated with the development of the obese-hyperglycaemic syndrome rather than being linked to the inheritance of the ob/ob genome as such.
Fifty-five patients with hormone refractory prostate cancer and painful bone metastases were randomised either to placebo or to clodronate 300 mg i.v. for 3 days, followed by oral clodronate 3200 mg for four weeks. Pain intensity was assessed using Visual Analogue Scales (VAS). Mean overall pain as well as mean pain during the best and worst periods were recorded. Forty-six patients were evaluable for efficacy. No significant differences were found between the two treatments. As regards mean worst pain a substantial numerical fall was registered for the treatment group, 21 mm, but the improvement was not significant compared to that of the placebo group. This was probably due to the limited number of patients (the study was prematurely ended due to problems recruiting patients). In conclusion, no significant differences were found between the treatment arm and the controls, in contrast to results from previous studies. Possible explanations are that the doses in this study were generally lower than in previous studies, the mean baseline pain was substantially lower and that the current study was placebocontrolled. Our data indicate that if clodronate is to be used for the alleviation of bone pain in prostate cancer, patients with high baseline should be selected and high intravenous doses should be given at start of the treatment.
Method of the bronchi and colon smooth myocytes dissociation in living rats with separation of cell fraction in the density gradient is worked out. Precise parameters of relative density of the bronchi and colon muscle cells are established. Smooth myocytes being a part of different organ-systems are shown to be characterized by different parameters of relative density.