Attenuation of Endocrine-Exocrine Pancreatic Communication in Type 2 Diabetes: Pancreatic Extracellular Matrix Ultrastructural Abnormalities

Melvin R. Hayden MD, Kamlesh Patel MD, Javad Habibi PhD, Deepa Gupta MD, Seema S. Tekwani MD, Adam Whaley-Connell DO, MSPH, James R. Sowers MD
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引用次数: 81

Abstract

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 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. Of importance, some pericyte cellular processes traverse both the connecting islet-exocrine interface 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, which are known to exist in prediabetes and overt T2DM in humans.

2型糖尿病胰腺内分泌-外分泌通讯衰减:胰腺细胞外基质超微结构异常
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,这种连接在啮齿动物模型和2型糖尿病(T2DM)患者中由于纤维化而丢失。胰岛-外分泌界面变宽可能导致胰岛和腺泡细胞间桥粒和粘附体连接的丧失,并与T2DM胰腺组织中由周细胞和炎症细胞组成的高细胞化有关。有组织的纤维性胶原蛋白与周细胞密切相关,周细胞可以分化成肌成纤维细胞-胰腺星状细胞。重要的是,一些周细胞过程穿过连接胰岛-外分泌界面和外分泌胰腺的内腺间质。在年轻动物模型和人类中,细胞旁分泌通讯和细胞外基质重塑纤维化的丧失可能导致胰岛素-腺泡-导管-肠促胰岛素肠激素轴功能失调,导致胰腺功能不全和胰高血糖素样肽缺乏,已知这在人类糖尿病前期和显性T2DM中存在。
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