Osei K, Henry M L, O'Dorisio T M, Tesi R J, Sommer B G, Ferguson R M
Department of Internal Medicine, Ohio State University Hospitals, Columbus.
Diabetes. 1990 Oct;39(10):1235-42. doi: 10.2337/diab.39.10.1235.
Successful heterotopic and denervated pancreas allograft transplantation (PAT) often results in normoglycemia and peripheral hyperinsulinemia in insulin-dependent (type I) diabetic recipients. The contribution of altered hepatic insulin extraction (HIE) to the resulting hyperinsulinemia in such patients remains uncertain. Furthermore, whether the denervated pancreas allografts exhibit beta-cell hyperresponsiveness to physiological and pharmacological stimulation is controversial. We evaluated beta-cell function and HIE after successful whole cadaveric PAT with systemic venous drainage in 13 type I diabetic patients before and after mixed-meal and intravenous glucose and glucagon administration. The results were compared with those of 5 nondiabetic patients with kidney transplantation only, who had native innervated pancreases with portal insulin delivery and were receiving an equivalent triple immunosuppressive therapy (cyclosporin, azathioprine, and prednisone), and 7 healthy control subjects with no family history of diabetes. After PAT, fasting and poststimulation serum glucose concentrations were normalized. PAT was associated with marked basal hyperinsulinemia (3- to 8-fold) as assessed by immunoreactive insulin (IRI) levels in type I diabetic patients (mean +/- SE 345 +/- 43 pM) compared with control subjects (43 +/- 14 pM) and nondiabetic kidney-transplantation patients (129 +/- 38 pM). After mixed-meal ingestion, the mean incremental integrated insulin area was similar in PAT patients (18 +/- 3 nM.min) compared with kidney-transplantation patients (20 +/- 4 nM.min) and healthy control subjects (21 +/- 3 nM.min). Basal serum C-peptide levels were significantly greater in PAT (1.72 +/- 0.13 nM) and kidney-transplantation (2.15 +/- 0.33 nM) patients than in healthy control subjects (0.50 +/- 0.10 nM; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
成功的异位和去神经支配胰腺移植（PAT）通常会使胰岛素依赖型（I型）糖尿病受者血糖正常化并出现外周高胰岛素血症。肝脏胰岛素提取（HIE）改变对这类患者高胰岛素血症的影响尚不确定。此外，去神经支配的胰腺移植是否对生理和药理刺激表现出β细胞高反应性也存在争议。我们评估了13例I型糖尿病患者在成功进行全尸体PAT并采用全身静脉引流后，在混合餐及静脉注射葡萄糖和胰高血糖素前后的β细胞功能和HIE。将结果与仅接受肾移植的5例非糖尿病患者进行比较，这些患者有天然神经支配的胰腺且通过门静脉输送胰岛素，正在接受等效的三联免疫抑制治疗（环孢素、硫唑嘌呤和泼尼松），以及7例无糖尿病家族史的健康对照者。PAT后，空腹和刺激后血清葡萄糖浓度恢复正常。与对照者（43±14 pM）和非糖尿病肾移植患者（129±38 pM）相比，通过免疫反应性胰岛素（IRI）水平评估，PAT使I型糖尿病患者出现显著的基础高胰岛素血症（3至8倍）（平均±标准误345±43 pM）。混合餐摄入后，PAT患者（18±3 nM·min）的平均增量整合胰岛素面积与肾移植患者（20±4 nM·min）和健康对照者（21±3 nM·min）相似。PAT患者（1.72±0.13 nM）和肾移植患者（2.15±0.33 nM）的基础血清C肽水平显著高于健康对照者（0.50±0.10 nM；P<0.01）。（摘要截断于250字）
