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胰岛素瘤以及非糖尿病和糖尿病患者胰腺胰岛中的胰岛淀粉样多肽。

Islet amyloid polypeptide in insulinoma and in the islets of the pancreas of non-diabetic and diabetic subjects.

作者信息

Toshimori H, Narita R, Nakazato M, Asai J, Mitsukawa T, Kangawa K, Matsuo H, Takahashi K, Matsukura S

机构信息

Internal Medicine, Miyazaki Medical College, Japan.

出版信息

Virchows Arch A Pathol Anat Histopathol. 1991;418(5):411-7. doi: 10.1007/BF01605927.

DOI:10.1007/BF01605927
PMID:2035254
Abstract

Amyloid deposition is a common pathological feature in insulinoma and in the islets of the pancreas in type-2 diabetic patients. The present immunohistochemical study revealed that normal B-cells, insulinoma, and amyloid deposits in insulinoma and diabetic pancreatic islets were commonly immunoreactive with antiserum to C-terminal synthetic tetradecapeptide of human islet amyloid polypeptide (IAPP) (24-37). Amyloid fibrils in insulinoma were also positive to IAPP by immunoelectron microscopy. A high level of IAPP was detected in the plasma and tissue of a insulinoma patient by radioimmunoassay suggesting that amyloid deposition in insulinoma is due to overproduction of IAPP. Amyloid deposits immunoreactive to IAPP were also seen in all diabetic pancreatic islets, but in no non-diabetic islets. There was much amyloid deposition in the islets of severe diabetics, whose B-cells demonstrated decreased immunoreactivities for IAPP and insulin. The IAPP content of the pancreas was 649.0 and 847.7 pg/mg wet weight in each of two diabetic patients, and 1034.6 and 1447.7 pg/mg wet weight in two non-diabetic patients. The present study revealed that IAPP is a bioactive peptide secreted from islet B-cells and are amyloidogenic peptide concerned in diabetogenensis and/or the progression of type-2 diabetes mellitus.

摘要

淀粉样蛋白沉积是胰岛素瘤以及2型糖尿病患者胰腺胰岛中的常见病理特征。目前的免疫组织化学研究显示,正常B细胞、胰岛素瘤以及胰岛素瘤和糖尿病胰腺胰岛中的淀粉样蛋白沉积物,通常与人胰岛淀粉样多肽(IAPP)(24 - 37)的C端合成十四肽抗血清发生免疫反应。胰岛素瘤中的淀粉样纤维通过免疫电子显微镜检查对IAPP也呈阳性。通过放射免疫测定法在一名胰岛素瘤患者的血浆和组织中检测到高水平的IAPP,这表明胰岛素瘤中的淀粉样蛋白沉积是由于IAPP的过度产生。在所有糖尿病胰腺胰岛中也可见到对IAPP呈免疫反应的淀粉样蛋白沉积物,但在非糖尿病胰岛中未见。重度糖尿病患者的胰岛中有大量淀粉样蛋白沉积,其B细胞对IAPP和胰岛素的免疫反应性降低。两名糖尿病患者胰腺的IAPP含量分别为649.0和847.7 pg/mg湿重,两名非糖尿病患者为1034.6和1447.7 pg/mg湿重。本研究表明,IAPP是一种从胰岛B细胞分泌的生物活性肽,是与糖尿病发生和/或2型糖尿病进展有关的淀粉样生成肽。

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本文引用的文献

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The relation of islet amyloid to the clinical type of diabetes.胰岛淀粉样变与糖尿病临床类型的关系。
Hum Pathol. 1981 Oct;12(10):917-22. doi: 10.1016/s0046-8177(81)80197-9.
2
Islet amyloid polypeptide-like immunoreactivity in the islet B cells of type 2 (non-insulin-dependent) diabetic and non-diabetic individuals.2型(非胰岛素依赖型)糖尿病患者及非糖尿病个体胰岛B细胞中的胰岛淀粉样多肽样免疫反应性
Diabetologia. 1987 Nov;30(11):887-92. doi: 10.1007/BF00274799.
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Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients.
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Immunohistology of islet amyloid polypeptide in diabetes mellitus: semi-quantitative studies in a post-mortem series.糖尿病中胰岛淀粉样多肽的免疫组织学:尸检系列的半定量研究
Virchows Arch A Pathol Anat Histopathol. 1992;421(4):339-44. doi: 10.1007/BF01660981.
从2型糖尿病患者富含淀粉样蛋白的胰腺中纯化和鉴定一种肽。
Proc Natl Acad Sci U S A. 1987 Dec;84(23):8628-32. doi: 10.1073/pnas.84.23.8628.
4
Islet amyloid in type 2 human diabetes mellitus and adult diabetic cats contains a novel putative polypeptide hormone.2型人类糖尿病和成年糖尿病猫的胰岛淀粉样蛋白含有一种新型的假定多肽激素。
Am J Pathol. 1987 Jun;127(3):414-7.
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Immunolocalization of islet amyloid polypeptide (IAPP) in pancreatic beta cells by means of peroxidase-antiperoxidase (PAP) and protein A-gold techniques.通过过氧化物酶-抗过氧化物酶(PAP)和蛋白A-金技术对胰岛β细胞中胰岛淀粉样多肽(IAPP)进行免疫定位。
Am J Pathol. 1988 Jan;130(1):1-8.
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Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes.胰岛淀粉样变、A细胞增多、B细胞减少及外分泌纤维化:2型糖尿病胰腺的定量变化
Diabetes Res. 1988 Dec;9(4):151-9.
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An islet amyloid peptide is derived from an 89-amino acid precursor by proteolytic processing.胰岛淀粉样多肽由一种含89个氨基酸的前体经蛋白水解加工产生。
J Biol Chem. 1988 Nov 25;263(33):17243-6.
8
Amylin found in amyloid deposits in human type 2 diabetes mellitus may be a hormone that regulates glycogen metabolism in skeletal muscle.在人类2型糖尿病淀粉样沉积物中发现的胰岛淀粉样多肽可能是一种调节骨骼肌糖原代谢的激素。
Proc Natl Acad Sci U S A. 1988 Oct;85(20):7763-6. doi: 10.1073/pnas.85.20.7763.
9
Pancreatic amylin and calcitonin gene-related peptide cause resistance to insulin in skeletal muscle in vitro.胰腺淀粉样多肽和降钙素基因相关肽在体外可导致骨骼肌对胰岛素产生抵抗。
Nature. 1988 Oct 13;335(6191):632-5. doi: 10.1038/335632a0.
10
Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells.人类胰岛素瘤以及糖尿病猫的胰岛中的淀粉样纤维源自一种也存在于正常胰岛细胞中的类神经肽蛋白。
Proc Natl Acad Sci U S A. 1987 Jun;84(11):3881-5. doi: 10.1073/pnas.84.11.3881.