Pyzdrowski K L, Kendall D M, Halter J B, Nakhleh R E, Sutherland D E, Robertson R P
Diabetes Center, University of Minnesota, Minneapolis 55455.
N Engl J Med. 1992 Jul 23;327(4):220-6. doi: 10.1056/NEJM199207233270402.
Transplantation of pancreatic islets, rather than whole pancreas, has been introduced as a treatment for diabetes mellitus. We studied five patients ranging in age from 12 to 37 years who had severe chronic pancreatitis for which they underwent total pancreatectomy followed by isolation and hepatic transplantation of their own islets.
All patients had remained insulin-independent for 1 to 7 1/2 years after transplantation. The numbers of islets transplanted ranged from 110,000 to 412,000. Islet function was assessed by measuring the plasma insulin responses to intravenous glucose and arginine and the plasma glucagon responses to hypoglycemia and arginine. In one patient, islet function was studied during catheterization of the hepatic vein, portal vein, and splenic artery and by analysis of a liver-biopsy specimen.
After transplantation, the mean (+/- SD) fasting plasma glucose concentration was 122 +/- 47 mg per deciliter (6.8 +/- 2.6 mmol per liter) and the hemoglobin A1c concentration was 6.0 +/- 0.8 percent in the five patients. The values were most abnormal--214 mg per deciliter (11.9 mmol per liter) and 7.3 percent, respectively--in the patient who received only 110,000 islets. The acute plasma insulin responses to glucose and to arginine in the five patients were 23 +/- 13 and 26 +/- 10 microU per milliliter (168 +/- 94 and 184 +/- 70 pmol per liter), respectively, as compared with 58 +/- 6 and 37 +/- 8 microU per milliliter (416 +/- 44 and 267 +/- 61 pmol per liter) in the normal subjects. The peak plasma glucagon responses to insulin and arginine were 21 +/- 4 and 65 +/- 36 pg per milliliter, respectively, as compared with 125 +/- 28 and 156 +/- 99 pg per milliliter in the normal subjects. All five patients had plasma epinephrine but not pancreatic polypeptide responses to hypoglycemia. The results of the hepatic-vein catheterization in one patient indicated that the transplanted islets released insulin and glucagon in response to arginine. Immunoperoxidase staining of this patient's liver-biopsy specimen showed that the islets contained insulin, glucagon, and somatostatin but not pancreatic polypeptide.
Intrahepatic transplantation of as few as 265,000 islets can result in the release of insulin and glucagon at appropriate times and in prolonged periods of insulin independence.
胰岛移植而非全胰腺移植已被引入作为糖尿病的一种治疗方法。我们研究了5例年龄在12至37岁之间的患有严重慢性胰腺炎的患者，他们接受了全胰切除术，随后进行了自身胰岛的分离和肝移植。
所有患者在移植后1至7.5年保持不依赖胰岛素。移植的胰岛数量在110,000至412,000个之间。通过测量静脉注射葡萄糖和精氨酸后血浆胰岛素反应以及低血糖和精氨酸后血浆胰高血糖素反应来评估胰岛功能。在1例患者中，在肝静脉、门静脉和脾动脉插管期间以及通过分析肝活检标本研究了胰岛功能。
移植后，5例患者的平均（±标准差）空腹血糖浓度为每分升122±47毫克（每升6.8±2.6毫摩尔），糖化血红蛋白浓度为6.0±0.8%。在仅接受110,000个胰岛的患者中，这些值最异常，分别为每分升214毫克（11.9毫摩尔/升）和7.3%。5例患者对葡萄糖和精氨酸的急性血浆胰岛素反应分别为每毫升23±13和26±10微单位（每升168±94和184±70皮摩尔），而正常受试者分别为每毫升58±6和37±8微单位（每升416±44和267±61皮摩尔）。对胰岛素和精氨酸的血浆胰高血糖素峰值反应分别为每毫升21±4和65±36皮克，而正常受试者分别为每毫升125±28和156±99皮克。所有5例患者对低血糖有血浆肾上腺素反应但无胰多肽反应。1例患者的肝静脉插管结果表明，移植的胰岛对精氨酸有胰岛素和胰高血糖素释放。该患者肝活检标本的免疫过氧化物酶染色显示，胰岛含有胰岛素、胰高血糖素和生长抑素，但不含胰多肽。
肝内移植少至265,000个胰岛可导致胰岛素和胰高血糖素在适当时间释放，并能长期保持不依赖胰岛素。
