The effects of a standard glucose tolerance test (GTT) and of pretreatment with aminophylline (AM) were examined in dogs with a reduced reserve of islet function prepared by partial removal of the pancreas and in normal intact dogs. Serum glucose, free fatty acid and insulin levels were measured. No significant differences were found before and after partial pancreatectomy when less than 50 per cent of the pancreas was removed or after sham operation. When AM was infused prior to the GTT, serum insulin levels were elevated to almost twice those obtained during a standard GTT. Dogs with less than 50 per cent of the pancreas remaining showed deterioration in GTT two weeks after operation, although the fasting blood sugar was normal except in one animal. The deterioration in GTT response progressed with time. Maintaining the animal on a high protein diet improved the GTT response. In chow-fed dogs with less than 50 per cent of the pancreas but no glucosuria or fasting hyperglycemia, prior AM infusion significantly improved the GTT and increased insulin secretion. In one dog with fasting hyperglycemia, AM did not cause improvement.

No abstract

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.

DAVIDSOX, J. K., CODDLING, J . A., A~D HAIST, R. E. 1968. Glycogen content of mouse hemidiaphragm as a bic~logic indicator of insulin action. Can. J. Physiol. Pharmacol. 46, 361-371.The mouse hemidiaphragrn insulin assay utilizes glycogen content as the biologic indicatev of insulin activity. It is statistically valid and has a mean index of precision of 0.22. The effects of alterations in the incubation medium showed that hyperosmolarity, hypo-osmolarity, and inadequate oxygenation reduced the glycogen content. There was a linear increase in glycogen content when it was plotted against the log of glucose concentration froin 3 to 20 mg/tnl. At these glucose concentrations, maximal insulin stirnulation increased glycogen content 50-1000/,. Optimal pH was 9.34-4.53 and optimal incubation time was 90 min. Insulin activity of native serum (NSIA) was low in peripheral vein and much higher in pancreatic vein. Itzsulin activity in acid alcoholic trcated dialyzed serum (TSIA) was much higher than NSIA in peripheral vein and significantly higher in pancreatic vein. NSIA was neutralizablc; the additional activity made manifest by treatment was not. The effect of NSIA, TS1.4, and standard insulin decreased in parallel tnanner with dilution.

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.