Attenuation of endocrine-exocrine pancreatic communication in type 2 diabetes: pancreatic extracellular matrix ultrastructural abnormalities.
Attenuation of endocrine-exocrine pancreatic communication in type 2 diabetes: pancreatic extracellular matrix ultrastructural abnormalities.
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2型糖尿病中内分泌 - 分泌胰腺传播的衰减：胰腺外基质基质超微结构异常。
DOI：
10.1111/j.1559-4572.2008.00024.x
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Sowers JR
中科院分区：
文献类型：
--
作者：
Hayden MR;Patel K;Habibi J;Gupta D;Tekwani SS;Whaley-Connell A;Sowers JR
超微结构观察显示，内分泌和外分泌胰腺之间存在连续的间质基质连接，在啮齿动物模型和人类2型糖尿病(T2 DM)模型中，这种连接因纤维化而丢失。在T2 DM胰腺组织中，胰岛外分泌界面(IEI)的增宽似乎导致桥粒的丢失并粘连胰岛和腺泡细胞之间的连接，并与由周细胞和炎性细胞组成的高细胞增多有关。有组织的纤维状胶原与周细胞密切相关，周细胞可分化为肌成纤维细胞-胰腺星状细胞。重要的是，一些周细胞突起既穿过连接的IEI，又穿过外分泌胰腺的腺泡内间质。在幼年动物模型和人类中，细胞旁分泌通讯的丧失和细胞外基质重塑纤维化可能导致胰岛素-腺泡-导管-胰岛素肠激素轴功能障碍，导致胰腺功能不全和已知存在于人类糖尿病前期和显性T2 DM的胰升糖素样肽缺乏。
Ultrastructural observations reveal a continuous interstitial matrix connection between the endocrine and exocrine pancreas, which is lost due to fibrosis in rodent models and humans with type 2 diabetes mellitus (T2DM). Widening of the islet exocrine interface (IEI) appears to result in loss of desmosomes and adherens junctions between islet and acinar cells and is associated with hypercellularity consisting of pericytes and inflammatory cells in T2DM pancreatic tissue. Organized fibrillar collagen was closely associated with pericytes, which are known to differentiate into myofibroblasts – pancreatic stellate cells. Importantly, some pericyte cellular processes traverse both the connecting IEI and the endoacinar interstitium of the exocrine pancreas. Loss of cellular paracrine communication and extracellular matrix remodeling fibrosis in young animal models and humans may result in a dysfunctional insulino-acinar-ductal – incretin gut hormone axis resulting in pancreatic insufficiency and glucagon like peptide deficiency known to exist in prediabetes and overt T2DM in humans.