Effects of parathyroid hormone infusion on glucose tolerance and glucose-stimulated insulin secretion in normal and uremic rats

Abstract

We used thyroparathyroidectomized (TPTX) rats with hypocalcemia to evaluate the effects of parathyroid hormone (PTH) infusion on glucose tolerance and glucose-stimulated insulin secretion in normal and uremic rats. Animals were subjected to oral glucose tolerance test (OGTT) and glucose-stimulated insulin secretion before and after TPTX or after their plasma calcium level was normalized by PTH infusion, vitamin D injection or calcium load. In both normal and uremic groups, TPTX produced a significant increase in area under the cure (AUC) of plasma glucose from 0 to 6 h in response to an oral glucose challenge and decrease plasma insulin level in response to glucose-stimulated insulin secretion. Before TPTX, uremic animals have a normal basal plasma insulin level (29±3 versus 31±2 μU/ml) and a normal glucose-stimulated insulin secretion, but significantly increase plasma glucose AUC in response to OGTT as compared with normal rats. TPTX worsen the response of glucose intolerance in uremic rats. After PTH infusion, vitamin D injection or calcium load, all rats in the response of OGTT and glucose-stimulated insulin secretion are recovered to the level before TPTX including normal and uremic rats, but uremic rats still have an abnormal glucose tolerance in response to OGTT. Uremic rats have a low basal plasma glucose level as compared with normal rats. TPTX significantly increase basal plasma glucose level in normal and uremic rats, but the uremic rats with TPTX have been found to elevate basal plasma glucose level to the range of normal rats. The basal plasma glucose level of normal rats with TPTX was recovered to the range before TPTX by PTH infusion, vitamin D injection or calcium load, but PTH infusion, vitamin D injection or calcium load did not decrease the level of basal plasma glucose in uremic rats with TPTX. All TPTX rats, including intact kidney or five-sixths Nx rats, were treated three times weekly by subcutaneous injection of 8 μg/kg l-thyroxin. These results indicate that uremia may produce thyroid dysfunction and PTH infusion did not affect the glucose tolerance in OGTT and glucose-stimulated insulin secretion in normal and uremic rats. In addition to PTH, other uremic toxins may be responsible for the glucose intolerance of uremia.