Kalsbeek Andries, la Fleur Susanne, Fliers Eric
Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam, The Netherlands ; Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands.
Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam, The Netherlands.
Mol Metab. 2014 Mar 19;3(4):372-83. doi: 10.1016/j.molmet.2014.03.002. eCollection 2014 Jul.
The incidence of obesity and type 2 diabetes mellitus (T2DM) has risen to epidemic proportions. The pathophysiology of T2DM is complex and involves insulin resistance, pancreatic β-cell dysfunction and visceral adiposity. It has been known for decades that a disruption of biological rhythms (which happens the most profoundly with shift work) increases the risk of developing obesity and T2DM. Recent evidence from basal studies has further sparked interest in the involvement of daily rhythms (and their disruption) in the development of obesity and T2DM. Most living organisms have molecular clocks in almost every tissue, which govern rhythmicity in many domains of physiology, such as rest/activity rhythms, feeding/fasting rhythms, and hormonal secretion. Here we present the latest research describing the specific role played by the molecular clock mechanism in the control of glucose metabolism and speculate on how disruption of these tissue clocks may lead to the disturbances in glucose homeostasis.
肥胖症和2型糖尿病(T2DM)的发病率已上升至流行程度。T2DM的病理生理学很复杂,涉及胰岛素抵抗、胰腺β细胞功能障碍和内脏肥胖。几十年来,人们已经知道生物节律紊乱(轮班工作时最为严重)会增加患肥胖症和T2DM的风险。基础研究的最新证据进一步激发了人们对日常节律(及其紊乱)在肥胖症和T2DM发生发展中所起作用的兴趣。大多数生物体几乎每个组织都有分子时钟,这些时钟控制着生理学许多领域的节律性,如休息/活动节律、进食/禁食节律和激素分泌。在此,我们展示了描述分子时钟机制在葡萄糖代谢控制中所起特定作用的最新研究,并推测这些组织时钟的紊乱如何可能导致葡萄糖稳态的失调。