Whittington K B, Solomon S S, Lu Z N, Selawry H P
Veterans Administration Medical Center, Memphis, Tennessee 38104.
Endocrinology. 1991 Jun;128(6):2671-7. doi: 10.1210/endo-128-6-2671.
The aim of this study was to examine insulin and glucagon secretory patterns in successfully transplanted spontaneously diabetic BB/Wor dp rats. Diabetic, BB/Wor dp rats received abdominal, intratesticular islet grafts of MHC-compatible BB/Wor dr donor rats without immunosuppression. After a period of 74 +/- 15 days of normoglycemia, they were given the following challenges: 1) glucose, by mouth, 2) a single oral dose of glipizide, with glucose, and 3) arginine, by iv infusion. The pertinent results included the mean fasting plasma glucose levels of control, Sprague-Dawley (C), of transplanted BB/Wor dp (T), and nontransplanted, insulin treated, diabetic BB/Wor dp (D), and they were, respectively, 97 +/- 4 mg/dl, 110 +/- 3 mg/dl, and 350 +/- 40 mg/dl. Fasting plasma insulin levels in C and T rats were 21.9 +/- 3 microU/ml, and 20.4 +/- 2 microU/ml, respectively. Fasting plasma glucagon levels in C, T, and D, were 37.8 +/- 5.7 pg/ml, 43.4 +/- 4.6 pg/ml, and 47.4 +/- 4.9 pg/ml, respectively. During oral glucose tolerance test, the pattern of insulin secretion in the C and T rats was identical with a peak attained at 15 min. Glucose caused a 70% suppression of plasma glucagon levels in C rats (P less than 0.01); T rats suppressed 14%, but this was not statistically significant; D rats failed to suppress. Glipizide plus glucose caused an improved glucose tolerance in T rats without significantly affecting insulin levels. In the same rats, glipizide resulted in a significant suppression of glucagon compared with levels in the presence of glucose alone. Arginine caused a minimal release of insulin in T rats and a major glucagon secretory response in D rats. Pancreatic glucagon content was significantly (P less than 0.03) lower in C and T, compared with D rats. Furthermore, the transplanted testes of T contained substantial amounts of glucagon. In summary, these data suggest that grafted testes in spontaneously diabetic BB/Wor dp rats contain both beta and alpha-cells and that these cells have the capacity to respond to specific secretagogues independently.
本研究的目的是检测成功移植的自发性糖尿病BB/Wor dp大鼠的胰岛素和胰高血糖素分泌模式。糖尿病BB/Wor dp大鼠接受来自MHC相容的BB/Wor dr供体大鼠的腹腔内、睾丸内胰岛移植，且未进行免疫抑制。在血糖正常74±15天后，对它们进行以下刺激：1）口服葡萄糖；2）口服单剂量格列吡嗪并同时口服葡萄糖；3）静脉输注精氨酸。相关结果包括对照Sprague-Dawley（C）大鼠、移植的BB/Wor dp（T）大鼠以及未移植的、接受胰岛素治疗的糖尿病BB/Wor dp（D）大鼠的空腹血浆葡萄糖平均水平，分别为97±4mg/dl、110±3mg/dl和350±40mg/dl。C组和T组大鼠的空腹血浆胰岛素水平分别为21.9±3μU/ml和20.4±2μU/ml。C组、T组和D组的空腹血浆胰高血糖素水平分别为37.8±5.7pg/ml、43.4±4.6pg/ml和47.4±4.9pg/ml。在口服葡萄糖耐量试验期间，C组和T组大鼠的胰岛素分泌模式相同，在15分钟时达到峰值。葡萄糖使C组大鼠的血浆胰高血糖素水平抑制70%（P<0.01）；T组大鼠抑制14%，但无统计学意义；D组大鼠未出现抑制。格列吡嗪加葡萄糖使T组大鼠的葡萄糖耐量改善，且对胰岛素水平无显著影响。在相同大鼠中，与仅存在葡萄糖时相比，格列吡嗪导致胰高血糖素显著抑制。精氨酸使T组大鼠胰岛素释放极少，使D组大鼠出现主要的胰高血糖素分泌反应。与D组大鼠相比，C组和T组大鼠的胰腺胰高血糖素含量显著降低（P<0.03）。此外，T组大鼠移植的睾丸中含有大量胰高血糖素。总之，这些数据表明，自发性糖尿病BB/Wor dp大鼠移植的睾丸中同时含有β细胞和α细胞，且这些细胞有能力独立对特定促分泌素作出反应。
