Insulin during infancy attenuates insulin-induced hypoglycemia in adult male rats.

To examine whether insulin during infancy affects later glucose regulation, 60 rat pups of both sexes were injected daily on postnatal Days 9-20 with either insulin (2 or 8 U/kg), 2-deoxy-D-glucose (2DG; 200 or 400 mg/kg), or saline. Two hours postinjection on Day 15, pups given insulin were hypoglycemic and pups given 2DG were hyperglycemic; both groups were normoglycemic at 6 h. The two insulin doses produced similar long-term effects, as did the 2DG doses, so doses were combined to make single insulin and 2DG groups. On Day 44, baseline plasma glucose for rats given insulin or 2DG during infancy was below saline control levels (111.3, 114.5, and 120.7 mg/dL, respectively, p < 0.05). On Days 60 and 62, plasma glucose was assessed 2 h after injection of 3 U/kg insulin; food was allowed between the insulin injection and the glucose test on only one of these days. When food was present after injection of insulin, the early treatments did not influence either amount of food ingested or plasma glucose levels. When food was withheld, however, males given insulin before weaning maintained a higher plasma glucose than did males given 2DG or saline before weaning (67.4, 40.1, and 16.4 mg/dL, respectively, p < 0.01); females were unaffected by the early treatment. Postweaning body weights did not differ from control values for rats given early insulin or 2DG. On Day 72, there were no effects of early treatment on plasma insulin, plasma glucose, liver weight, or kidney weight. These results suggest that preweaning exposure to insulin attenuates the hypoglycemia of adult males given insulin without food.

Effects of streptozotocin diabetes and fasting on intracellular sodium and adenosine triphosphate in rat soleus muscle.

The hypothesis that part of the insulin transduction system consists of a co-ordinated stimulation of the Na pump and of Na-H exchange by the hormone (Moore, 1981) requires that insulin plays a physiological role in the regulation of intracellular Na+. Moreover, this model predicts that in hypoinsulinaemic states, such as diabetes and fasting, intracellular pH and intracellular ATP levels would be depressed. The present study tests the hypothesis that in hypoinsulinaemic states intracellular Na+ is increased and intracellular ATP is decreased by measuring these parameters in soleus muscles removed from both diabetic and fasted rats. When rats were made diabetic by injection of streptozotocin (SZ) plasma insulin significantly decreased by 24 hr and plasma glucose and triglyceride levels increased. Intracellular Na+ was significantly elevated by 48 hr after injection of SZ. The elevation ranged from 18 to 48% and persisted for the duration of the experimental observation (up to 28 days). Intracellular ATP decreased significantly by the seventh day after SZ injection and remained depressed by about 24% for the duration (35 days) of the observation. In one series, a significant negative correlation was seen between plasma insulin levels and intracellular Na+ of both SZ-diabetic animals and their controls. Intracellular Na+ also significantly increased when hypoinsulinaemia was induced by fasting. Again, intracellular ATP did not decrease until after the elevation of intracellular Na+. After 72 hr of fasting, intracellular ATP was still decreased in spite of normal plasma glucose levels. Insulin therapy of SZ diabetic rats restored intracellular ATP and plasma glucose to normal, but did not restore intracellular Na+ to normal levels. The results confirm two predictions of the 'insulin transduction system model (Moore, 1981). Most strongly supported is that part of the model which indicates that the Na pump is regulated by physiological levels of insulin. This is especially convincing since hypoinsulinaemia produced by a non-pharmacological procedure, fasting, was associated with an increase in intracellular Na+.