Cytomegalic Virus-Associated Insulitis in Diabetic Octodon degus
Cytomegalic Virus-Associated Insulitis in Diabetic Octodon degus
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糖尿病八齿八齿鼠巨细胞病毒相关性胰岛炎
DOI：
10.1177/030098587901600520
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发表时间：
1979
影响因子：
2.4
通讯作者：
J. Murphy
中科院分区：
文献类型：
--
作者：
J. Fox;J. Murphy
男性青少年发病糖尿病的发生与几种病毒感染有关，包括腮腺炎、风疹和柯萨奇病毒[4,6,171]。伴有或不伴有胰岛素炎的胰腺炎也可发生于腮腺炎、风疹和柯萨奇病毒感染。婴儿巨细胞病毒感染在包括胰腺在内的几个器官有感染的形态学征象的报道并不少见。胰腺炎和胰岛素炎有时在胰岛细胞、腺泡和导管上皮细胞中出现特征性的核和细胞质包涵体。全身性巨细胞病毒感染也与免疫缺陷患者相关，其累及胰腺的情况与新生儿相似[8,13,19]。然而，病毒诱导糖尿病的最有说服力的证据是reo-3和脑心肌炎病毒（IS）在小鼠中产生糖尿病。在感染巨细胞病毒的免疫抑制小鼠的胰岛β细胞中也发现了特征性包涵体[1]。我们最近报道了degu （Ocrodon degu）的糖尿病[5，LO, 141]。我们现在报道了胰岛细胞（图1）、腺泡细胞（图2）和胰管细胞中的特征性巨细胞病毒包涵体。每一个先前死亡的人的连续胰腺切片复查巨细胞病毒包涵体。28个I型胰腺中有14个含有这样的包涵体。这14个degus和另外10个在唾液腺中也有包含物。24名患者中有10人有糖尿病的临床症状。胰腺的大多数包涵体位于腺泡细胞中，但无论细胞受何种影响，几乎每个包含包涵体的胰腺都可发现某种程度的胰岛素炎。（图一）。在电子显微镜下，在糖尿病患者胰腺腺泡组织中可见许多直径约200纳米的球形DNA病毒样颗粒（图3）。这些颗粒可能是巨细胞病毒，因为它们在形状和大小上与人类和其他动物的巨细胞病毒颗粒相似，并且在同一胰腺中光镜下发现了许多典型的巨细胞病毒包涵体。28例（15%）死鼠中有4例出现高血糖、空腹血糖升高或糖耐量异常。巨细胞病毒包涵体见于7例糖尿病患者和7例无糖尿病患者的胰腺。我们之前报道的其他大胰腺病变包括L.angerhans胰岛的肥大和增生（图4）和淀粉样变（图5）。胰岛增生和肥厚发生在14例胰腺中伴包涵体。24例胰腺中有6例胰岛淀粉样变。其中四个在胰腺组织中有包涵体。6例胰岛淀粉样变患者通常有一个或多个胰岛伴淀粉样沉积并伴有胰岛素炎（图4）。巨细胞病毒感染患者的胰岛素炎在形态学上与男性糖尿病的幼年发病相似。胰岛淀粉样变的观察是有趣的，因为这也在男性糖尿病患者中发现。已知一种特殊形式的淀粉样蛋白（淀粉样蛋白AA）与慢性感染有关[181]。其他几个动物模型。包括几种糖尿病小鼠和棘鼠。胰岛增生。161. 男人。
The development of juvenile onset diabetes in man has been associated with several viral infections, including mumps, rubella and coxsackie virus [4, 6, 171. Pancreatitis with or without insulitis also has occurred with mumps, rubella and coxsackie virus infections. Reports of generalized cytomegalovirus infections of infants with morphologic signs of infection in several organs, including the pancreas, are not infrequent. Pancreatitis and insulitis sometimes occur with characteristic nuclear and cytoplasmic inclusion bodies in islet cells and acinar and ductal epithelial cells. Generalized cytomegalovirus infections also have been associated with immunodeficient patients and the pancreatic involvement has been similar to that reported in neonates [8, 13, 19). The most persuasive evidence for virus induced diabetes, however, has been the production of diabetes in mice by both reo-3 and encephalomyocarditis virus 12, IS]. Characteristic inclusions also have been found in islet beta cells in immunosuppressed mice infected with cytomegalovirus [I]. We recently reported diabetes mellitus in degus (Ocrodon degu) [5 , LO, 141. We now report characteristic cytomegalovirus inclusion bodies in islet cells (fig. 1) and acinar (fig. 2) and ductal cells of degu pancreases. Serial sections of pancreas of every degu previously necropsied were reexamined for cytomegalovirus inclusions. Fourteen of 28 I pancreases contained such inclusion bodies. These 14 degus and 10 others also had inclusions in the salivary glands. Ten of the 24 degus had clinical signs of diabetes. Most inclusions in the pancreas were in acinar cells, but regardless of the cell affected some degree of insulitis was found in almost every pancreas that contained inclusions. (fig. I ) . With electron microscopy, many spherical DNA virus-like particles about 200 nanometers in diameter were seen in pancreatic acinar tissue from a diabetic degu (fig. 3). These particles probably are cytomegalovirus because they are similar in shape and size to cytomegalovirus particles in man and other animals, and numerous characteristic cytomegalovirus inclusions were found by light microscopy in the same pancreas. Clinical evidence of diabetes in the degu was indicated by glucosuria, elevated fasting blood glucose or abnormal glucose tolerance in 4 I of 28 I ( 15%) degus necropsied. Cytomegalovirus inclusions were seen in the pancreas of seven degus with and seven without clinical evidence of diabetes. Other lesions in the degu pancreas that we previously reported included hypertrophy and hyperplasia (fig. 4) and amyloidosis (fig. 5) of the islets of L.angerhans. Hyperplasia and hypertrophy of islets occurred in the 14 degus with inclusions in the pancreas. Amyloidosis of the islets was noted in six of 24 pancreases. four of which had inclusions in the pancreatic tissue. The six with amyloidosis of the islets usually had one or more islets with insulitis accompanying the amyloid deposit (fig. 4). The insulitis in degus with cytomegalovirus infections is morphologically similar to that in juvenile onset diabetes in man [7]. The observation of islet amyloidosis is intriguing because this also is found in diabetes in man. and a specific form of amyloid (amyloid AA) is known to be associated with chronic infections [ 181. Several other animal models. including several strains of diabetic mice and the spiny mice. have hyperplasia of pancreatic islets 19. 161. Man