Biomedical subjects
Publications and source records attributed to M Koser.
Nineteen patients with 20 axillary-subclavian vein thromboses were examined by venography. In 70% the axillary and subclavian veins were involved in continuity. The innominate vein was seldom involved, although demonstration of this was difficult. In 50% of the patients the thrombosis was a secondary phenomenon associated with either breast carcinoma, central venous pressure lines, heroin addiction, or cervical rib.
1. When pancreatic islets are preincubated for 20h in the presence of glucose (83.3mM) and thereafter transferred to a glucose-free medium, theophylline (1.4mM) provokes a dramatic stimulation of insulin release. This phenomenon does not occur when the islets are preincubated for either 20h at low glucose concentration (5.6mM) or only 30 min at the high glucose concentration (83.3mM). 2. The insulinotropic action of theophylline cannot be attributed to contamination of the islets with exogenous glucose and is not suppressed by mannoheptulose. 3. The secretory response to theophylline is an immediate phenomenon, but disappears after 60min of exposure to the drug. 4. The release of insulin evoked by theophylline is abolished in calcium-depleted media containing EGTA. Theophylline enhances the net uptake of 45Ca by the islets. 5. Glycogen accumulates in the islets during the preincubation period, as judged by both ultrastructural and biochemical criteria. Theophylline significantly increases the rate of glycogenolysis during the final incubation in the glucose-free medium. 6. The theophylline-induced increase in glycogenolysis coincides with a higher rate of both lactate output and oxidation of endogenous 14C-labelled substrates. 7. These data suggest that stimulation of glycolysis from endogenous stores of glycogen is sufficient to provoke insulin release even in glucose-deprived islets, as if the binding of extracellular glucose to hypothetical plasma-membrane glucoreceptors is not an essential feature of the stimulus-secretion coupling process.
Alpha-D-Glucose is known to exert more marked insulinotropic action than B-D-glucose. Both anomers are phosphorylated at the same rate by rat islet homogenates. The islet glucose-6-phosphate dehydrogenase displays a preferential affinity towards beta-D-glucose-6-phosphate, and this coincides with a higher sorbitol content in the islets exposed to beta-D-glucose. On the contrary, the islet phosphoglucose isomerase is stereospecific for alpha-D-glucose 6-phosphate and, hence, the concentration of glucose 6-phosphate is lower and that of the alpha-anomer to lactate and CO2 is also higher than that of beta-D-glucose. This increased glycolytic flux is associated with a more marked inhibitory action on 14Ca efflux, a more pronounced stimulation of 45Ca net uptake and a higher rate of insulin release in the islets exposed to alpha-D-glucose. The more marked insulinotropic action of alpha- as a distinct from beta-D-glucose is thus compatible with the view that glycolysis represents the key component of the sensor device through which glucose is identified in the pancreatic B-cell as a stimulus for insulin release.
Explore the source record for details and available documents.
Explore the source record for details and available documents.