人胰淀素的研究进展

An Updated Review of Human Amylin

人胰淀素(hIAPP)是由胰岛?细胞合成分泌、37个氨基酸组成的多肽类激素,与胰岛素、胰高血糖素等协同调节糖稳态。hIAPP可表现为生理药理状态下的单体(monomer)以及病理状态下的寡聚体(oligomer,α-螺旋结构)与纤维体(fibril,β片层折叠)。hIAPP单体的生理药理功能如下:1) 影响胰岛素与胰高血糖素的分泌;2) 延缓胃排空,降低餐后血糖;3) 升高肾素与血管紧张素II,调节肾生长;4) 升高醛固酮,降低血钙;5) 调节骨密度;6) 舒张血管,调节血流动力学;7) 调节免疫效应。hIAPP单体可诱导调节T细胞分化,从而调节炎症反应和免疫因子的分泌。部分一过性hIAPP寡聚体可引发胰岛β细胞凋亡,造成β细胞功能失常。由hIAPP纤维体折叠形成的淀粉样沉积,可保护胰岛避免自身免疫攻击。hIAPP不足或者hIAPP纤维体缺乏,是自身免疫性糖尿病的特征。hIAPP在肥胖以及糖尿病、自身免疫、骨质疏松等疾病的防治过程中,具有潜在应用前景。

Human amylin/islet amyloid polypeptide (hIAPP) is a 37-amino acid polypeptide synthesized and secreted from islet β-cells. hIAPP orchestrates with insulin and glucagon to maintain glucose homeostasis. Conformation of the physiological-pharmacological hIAPP monomers can transform into an α-helical oligomer and eventually β-pleated sheet fibrils. The physiological-pharmacological effects of hIAPP monomers are as follows: 1) playing with insulin and glucagon to regulate blood glucose levels, 2) delaying gastric empty, 3) modulating renal growth by increased levels of renin, angiotensin II, and aldosterone, 4) lowering blood calcium level by calcitonin-like action, 5) regu-lating bone density and minimizing the risk of osteoporosis, 6) dilating blood vessels for homodynamic changes, and 7) modulating autoimmune response predominantly by the induction of regu-latory T cells and regulation of cytokines and inflammatory reactions. The autoimmune-modulating action of hIAPP is a rather novel finding. The transient hIAPP oliomers might be toxic and have implicated in the islet β-cell apoptosis and dysfunction. Islet amyloid deposits dominantly com-promising of hIAPP fibrils may be protective against self-destruction in autoimmune diabetes. Therefore, the neuroendocine hIAPP indeed has multiple potentials in the prevention and treatment of chronic diseases such as obesity, diabetes, autoimmune disorder, and osteoporosis.