Effect on pancreatic blood flow and insulin output of infusions of aminophylline, galactose and galactose plus aminophylline into an isolated in situ portion of pancreas.

Effects on pancreatic blood flow and insulin output of infusions of aminophylline, galactose and galactose plus aminophylline were studied on an isolated portion of dog pancreas with only one afferent and one efferent blood vessel remaining. Infusion of aminophylline at 8 mg per minute gave significant increases in pancreatic blood flow and insulin output. Infusion of galactose at 7.2 mg per minute significantly increased insulin output. Galactose (7.2 mg per minute) plus aminophylline (8 mg per minute) also increased both pancreatic blood flow and insulin output. Pancreatic venous plasma glucose levels rose slightly during these infusions. Since the perfusing plasma contained a fasting level of glucose both aminophylling and galactose when infused alone or together were infused in the presence of approximately 1 mg/ml glucose. Pancreatic blood flow and insulin output increased to a lesser extent when aminophylline was infused along with galactose, the when aminophylline was infused alone.

Effects of age and of fasting on the responsiveness of the insulin-secreting mechanism of the islets of Langerhans to glucose.

Insulin responsiveness to glucose of isolated islets of Langerhans was studied in 'younger' and 'older' rats after feeding and fasting for various lengths of time. In 'younger' rats, after prolonged fasting (168 h) the threshold for glucose-stimulated insulin secretion was increased. This was not evident in islets from 'younger' rats fasted for 48 or 89 h. Reductions in increments of insulin secretion with increments in glucose, in the maximum insulin secreted and in the total extractable insulin of the islets were apparent after fasting for 48, 89 and 168 h as compared with islets from fed rats. In 'older' rats, prolonged fasting caused an increase in the threshold for glucose-stimulated insulin secretion, reduced incremental insulin secretion, reduced maximum insulin secretion and reduced total extractable insulin. However, the responses of islets from fed 'older' rats were similar to those of fasted (168 h) 'younger' rats. The threshold levels were similar, and there were no significant differences between increments in insulin secretion, maximum insulin secretion and insulin content of the islets. These experiments show that the responsiveness of islets of Langerhans in rats can be altered by age and fasting.

Insulin biosynthesis: the monoaminergic mechanisms and the specificity of "glucoreceptor".

Islets of Langerhans, isolated from the rat, did not synthesize insulin in the presence of L-glucose, fructose, galactose, 3-0-methyl glucose or sorbitol. A small amount of insulin was synthesized in the presence of glucosamine. Addition of caffeine to these compounds did not enhance the biosynthesis of insulin. It is suggested that the specificity of the membrane surface "glucoreceptor", if it exists, may be rather narrow, at least with respect to insulin biosynthesis. Serotonin, dopamine and isoproterenol did not inhibit or enhance insulin biosynthesis induced by glucose. Propranolol also failed to modify insulin synthesis in the absence or presence of isoproterenol. It is concluded that the monoaminergic mechanisms do not affect insulin biosynthesis in spite of their significant regulatory influence on insulin release. Methysergide, at the concentration reported to potentiate insulin release induced by glucose and tolbutamide in rabbit, strongly inhibited insulin biosynthesis.