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

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Abstract
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+.