Department of Pharmacological and Biomolecular Sciences (DiSFeB), Università degli Studi di Milano, 20134 Milan, Italy.
Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MA 48106, USA.
Biomolecules. 2023 Jan 24;13(2):224. doi: 10.3390/biom13020224.
Pancreatic β-cells, by secreting insulin, play a key role in the control of glucose homeostasis, and their dysfunction is the basis of diabetes development. The metabolic milieu created by high blood glucose and lipids is known to play a role in this process. In the last decades, cholesterol has attracted significant attention, not only because it critically controls β-cell function but also because it is the target of lipid-lowering therapies proposed for preventing the cardiovascular complications in diabetes. Despite the remarkable progress, understanding the molecular mechanisms responsible for cholesterol-mediated β-cell function remains an open and attractive area of investigation. Studies indicate that β-cells not only regulate the total cholesterol level but also its redistribution within organelles, a process mediated by vesicular and non-vesicular transport. The aim of this review is to summarize the most current view of how cholesterol homeostasis is maintained in pancreatic β-cells and to provide new insights on the mechanisms by which cholesterol is dynamically distributed among organelles to preserve their functionality. While cholesterol may affect virtually any activity of the β-cell, the intent of this review is to focus on early steps of insulin synthesis and secretion, an area still largely unexplored.
胰岛β细胞通过分泌胰岛素在控制葡萄糖稳态方面发挥着关键作用，其功能障碍是糖尿病发展的基础。已知高血糖和高血脂所形成的代谢环境在这一过程中发挥作用。在过去的几十年中，胆固醇引起了人们的极大关注，不仅因为它能严格控制β细胞的功能，还因为它是降脂治疗的靶点，该治疗旨在预防糖尿病的心血管并发症。尽管取得了显著进展，但了解胆固醇介导的β细胞功能的分子机制仍然是一个开放且有吸引力的研究领域。研究表明，β细胞不仅调节总胆固醇水平，还调节其在细胞器内的重新分布，这一过程由囊泡和非囊泡运输介导。本文综述的目的是总结目前关于胰岛β细胞中胆固醇稳态是如何维持的观点，并提供胆固醇在细胞器之间动态分布以维持其功能的机制的新见解。虽然胆固醇可能影响β细胞的几乎任何活动，但本文的目的是重点关注胰岛素合成和分泌的早期步骤，这一领域仍在很大程度上未被探索。
