Kissler H J, Gepp H, Schwille P O
Division of Experimental Surgery and Endocrine Research Laboratory, University of Erlangen, Maximiliansplatz, D-91054 Erlangen, Germany.
Res Exp Med (Berl). 1999 Oct;199(2):73-85. doi: 10.1007/s004330050134.
Heterotopic pancreas transplantation in type I diabetic patients does not correct hyperglucagonemia, which is thought to be due to insufficiently suppressed glucagon release by the host pancreas. The diabetogenic effects of glucagon then have to be corrected by higher than normal insulin secretion from the transplant, with the attendant risk of earlier loss of islet cell function, and development of atherosclerosis. To establish whether this situation can be prevented, we investigated glucose homeostasis and blood lipids, as well as fecal fat and chymotrypsin as indicators for pancreatic exocrine function 14 weeks after orthotopic pancreas transplantation in inbred rats. The pancreas was resected before orthotopic transplantation of the donor pancreas with portal venous drainage (n=8). Laparotomized animals served as controls (n=8). Basal plasma glucagon, basal plasma insulin to glucagon molar ratio, and basal and integrated incremental responses of plasma glucose, insulin, and C-peptide after an oral glucose load (2 g/kg body weight) were similar in both groups. However, hepatic insulin clearance was slightly but significantly lower in the transplanted group (1.1+/- 0.1 vs 1.6+/-0.2; P<0.05). Basal plasma levels of free fatty acids, phospholipids, triglycerides, cholesterol, low-density lipoproteins, and high-density lipoproteins were unchanged after transplantation. Also unchanged were fecal fat and chymotrypsin levels, thus indicating preserved pancreatic exocrine function. We concluded that orthotopic pancreas transplantation with portal venous drainage achieves almost optimal metabolic control with respect to endocrine and exocrine pancreatic function as well as blood lipids. This technique could therefore be used to treat combined endocrine and exocrine insufficiency in chronic pancreatitis and thus enlarges the spectrum of indications for pancreas transplantation.
I型糖尿病患者进行异位胰腺移植并不能纠正高胰高血糖素血症，这被认为是由于宿主胰腺对胰高血糖素释放的抑制不足所致。然后，必须通过移植物高于正常水平的胰岛素分泌来纠正胰高血糖素的致糖尿病作用，随之而来的是胰岛细胞功能早期丧失和动脉粥样硬化发展的风险。为了确定这种情况是否可以预防，我们在近交系大鼠原位胰腺移植14周后，研究了葡萄糖稳态和血脂，以及粪便脂肪和胰凝乳蛋白酶作为胰腺外分泌功能的指标。在原位移植供体胰腺并进行门静脉引流之前，将胰腺切除（n = 8）。开腹动物作为对照（n = 8）。两组的基础血浆胰高血糖素、基础血浆胰岛素与胰高血糖素的摩尔比，以及口服葡萄糖负荷（2 g/kg体重）后血浆葡萄糖、胰岛素和C肽的基础及累积增量反应相似。然而，移植组的肝脏胰岛素清除率略低但有显著差异（1.1±0.1对1.6±0.2；P<0.05）。移植后游离脂肪酸、磷脂、甘油三酯、胆固醇、低密度脂蛋白和高密度脂蛋白的基础血浆水平没有变化。粪便脂肪和胰凝乳蛋白酶水平也没有变化，因此表明胰腺外分泌功能得以保留。我们得出结论，门静脉引流的原位胰腺移植在胰腺内分泌和外分泌功能以及血脂方面实现了几乎最佳的代谢控制。因此，该技术可用于治疗慢性胰腺炎合并的内分泌和外分泌功能不全，从而扩大胰腺移植的适应证范围。
