Narita R, Toshimori H, Nakazato M, Kuribayashi T, Toshimori T, Kawabata K, Takahashi K, Masukura S
Department of Internal Medicine, Miyazaki Medical College, Japan.
Diabetes Res Clin Pract. 1992 Jan;15(1):3-14. doi: 10.1016/0168-8227(92)90060-5.
Twenty pancreata of non-diabetic patients and 17 pancreata of diabetic patients, including two patients with insulin-dependent diabetes mellitus, were immunohistochemically studied using antiserum against human islet amyloid polypeptide (IAPP). The islet beta cells in non-diabetic patients were immunoreactive for both IAPP and insulin. Amyloid deposition immunoreactive for IAPP was detected in six of 20 pancreata of non-diabetic patients. The plasma glucose level of three of these six patients was elevated to more than 200 mg/dl, and that of the other three ranged from 143 to 162 mg/dl; all six were receiving intravenous hyper-alimentation and had no history of diabetes prior to treatment. Amyloid deposition was present in all patients with non-insulin-dependent diabetes mellitus (NIDDM). The deposition was absent in the pancreata of two secondary diabetic patients, one of whom had received steroid hormone for bronchial asthma and the other of whom had liver cirrhosis with hepatocellular carcinoma; deposition was also absent in the pancreas of a patient with impaired glucose tolerance diagnosed on a 75-g oral glucose load. Heterogeneous expression of immunoreactivities of beta cells for insulin and for IAPP was present, suggesting independently regulated production and secretion of the peptides. Immunoreactivity of beta cells was more sensitively decreased for IAPP than for insulin in the islets of NIDDM patients. The decreased immunoreactivity for IAPP suggested an initial stage of disturbed beta-cell function, even if the immunoreactivity for insulin was apparently intact or the amyloid deposition in the islets was insignificant. The degree of amyloid deposition immunoreactivity for IAPP did not necessarily reflect the severity of diabetes mellitus. Amyloid deposits were seen at the narrow spaces beneath the insular capsule of connective tissues and the perivascular region or, in some cases, occupying the whole of the islet. The diabetogenic role of IAPP is unclear, but the deposition might be an accelerating factor which disturbs beta-cell function.
使用抗人胰岛淀粉样多肽（IAPP）抗血清，对20例非糖尿病患者的胰腺和17例糖尿病患者的胰腺进行了免疫组织化学研究，其中包括2例胰岛素依赖型糖尿病患者。非糖尿病患者的胰岛β细胞对IAPP和胰岛素均有免疫反应性。在20例非糖尿病患者的胰腺中，有6例检测到对IAPP有免疫反应性的淀粉样沉积。这6例患者中有3例的血浆葡萄糖水平升高至200mg/dl以上，另外3例的血浆葡萄糖水平在143至162mg/dl之间；所有6例患者均接受静脉高营养治疗，治疗前无糖尿病病史。所有非胰岛素依赖型糖尿病（NIDDM）患者均有淀粉样沉积。2例继发性糖尿病患者的胰腺中未出现沉积，其中1例因支气管哮喘接受类固醇激素治疗，另1例患有肝硬化伴肝细胞癌；在口服75g葡萄糖耐量试验诊断为糖耐量受损的患者的胰腺中也未出现沉积。β细胞对胰岛素和IAPP的免疫反应性存在异质性表达，提示这些肽的产生和分泌是独立调节的。在NIDDM患者的胰岛中，β细胞对IAPP的免疫反应性比胰岛素更敏感地降低。IAPP免疫反应性降低提示β细胞功能紊乱的初始阶段，即使胰岛素免疫反应性明显正常或胰岛中的淀粉样沉积不明显。IAPP免疫反应性淀粉样沉积的程度不一定反映糖尿病的严重程度。淀粉样沉积物见于结缔组织胰岛被膜下方的狭窄间隙和血管周围区域，或在某些情况下占据整个胰岛。IAPP的致糖尿病作用尚不清楚，但这种沉积可能是干扰β细胞功能的一个加速因素。
