Chen S M, Young T K, Ho L T
Department of Medical Research and Education, Veterans General Hospital, Taipei, Taiwan, ROC.
Diabetes Res Clin Pract. 1998 Aug;41(2):85-94. doi: 10.1016/s0168-8227(98)00067-9.
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 microU/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 micrograms/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.
我们使用甲状旁腺切除（TPTX）致低钙血症的大鼠来评估甲状旁腺激素（PTH）输注对正常大鼠和尿毒症大鼠葡萄糖耐量及葡萄糖刺激的胰岛素分泌的影响。在TPTX前、TPTX后或通过PTH输注、维生素D注射或钙负荷使血浆钙水平恢复正常后，对动物进行口服葡萄糖耐量试验（OGTT）和葡萄糖刺激的胰岛素分泌检测。在正常组和尿毒症组中，TPTX均导致口服葡萄糖刺激后0至6小时血浆葡萄糖曲线下面积（AUC）显著增加，以及葡萄糖刺激的胰岛素分泌时血浆胰岛素水平降低。在TPTX前，尿毒症动物的基础血浆胰岛素水平正常（29±3对31±2微单位/毫升），葡萄糖刺激的胰岛素分泌也正常，但与正常大鼠相比，OGTT时血浆葡萄糖AUC显著增加。TPTX使尿毒症大鼠的葡萄糖不耐受反应恶化。在PTH输注、维生素D注射或钙负荷后，所有大鼠（包括正常大鼠和尿毒症大鼠）的OGTT反应及葡萄糖刺激的胰岛素分泌均恢复到TPTX前的水平，但尿毒症大鼠对OGTT的葡萄糖耐量仍异常。与正常大鼠相比，尿毒症大鼠的基础血浆葡萄糖水平较低。TPTX使正常大鼠和尿毒症大鼠的基础血浆葡萄糖水平显著升高，但发现TPTX后的尿毒症大鼠基础血浆葡萄糖水平升高至正常大鼠范围。TPTX的正常大鼠通过PTH输注、维生素D注射或钙负荷使基础血浆葡萄糖水平恢复到TPTX前范围，但PTH输注、维生素D注射或钙负荷并未降低TPTX的尿毒症大鼠的基础血浆葡萄糖水平。所有TPTX大鼠，包括完整肾脏或五分之六肾切除大鼠，每周皮下注射8微克/千克L-甲状腺素三次。这些结果表明，尿毒症可能导致甲状腺功能障碍，且PTH输注不影响正常大鼠和尿毒症大鼠OGTT中的葡萄糖耐量及葡萄糖刺激的胰岛素分泌。除PTH外，其他尿毒症毒素可能是尿毒症葡萄糖不耐受的原因。
