Collagenase—isolated pancreatic islets collected from adult rats were incubated with glucose, tolbutamide or aminophylline (a soluble salt of theophylline). Indices of activity were insulin released into the medium, and oxidation of glucose labeled either in the C–l or C–6 position. Whereas glucose alone (16.5mM) produced a highly significant increase in insulin release, tolbutamide (0.1 mg/ml) or aminophylline (1 or 10mM) were ineffective by themselves. Both, however, potentiated the effect of glucose. If production of 14–CO2 from labeled glucose (SA 1.0 μi/mg) was measured in the presence of glucose, addition of neither tolbutamide nor aminophylline changed the number of 14–CO2 counts. If the islets were obtained from animals pretreated with 6–Aminonicotinamide, glucose released significantly less insulin, and less C–l carbon was incorporated into 14–CO2, indicating possible interference with adequate functioning of the pentose phosphate shunt. Addition of tolbutamide did not restimulate oxidation of glucose by this pathway, although it continued to release large amounts of insulin. Aminophylline in the presence of glucose induced a dose—dependent insulin release which was significantly reduced in islets from 6–Aminonicotinamide pretreated animals. Oxidation of labeled glucose via the pentose phosphate shunt was also depressed, and aminophylline did not overcome this block. It is concluded that glucose requires oxidation of its carbon in position 1 to induce insulin release. Tolbutamide potentiates the action of glucose; it will do so even if 14–C–l glucose oxidation is depressed by pretreatment with 6–Aminonicotinamide. Similar to glucose, the insulin releasing action of aminophylline is markedly reduced if oxidation of C–l glucose is inhibited. Thus a difference in action emerges between glucose and aminophylline on the one hand and tolbutamide on the other. It is speculated that tolbutamide can substitute for a malfunctioning pentose phosphate shunt. (Endocrinology91: 33, 1972)
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Ammon et al. (1972) studied this question.