The islet circadian clock: entrainment mechanisms, function and role in glucose homeostasis.
Circadian regulation of glucose homeostasis and insulin secretion has long been appreciated as an important feature of metabolic control in humans. Circadian disruption is becoming increasingly prevalent in today's society and is likely responsible in part for the considerable rise in type 2 diabetes (T2DM) and metabolic syndrome worldwide. Thus, understanding molecular mechanisms driving the inter-relationship between circadian disruption and T2DM is important in context of disease prevention and therapeutics. In this regard, the goal of this article is to highlight the role of the circadian system, and islet circadian clocks in particular, as potential regulators of β-cell function and survival. To date, studies have shown that islet clocks respond to changes in feeding patterns, and regulate a multitude of critical cellular processes in insulin secreting β-cells (e.g. insulin exocytosis, mitochondrial function and response to oxidative stress). Subsequently, either genetic or environmental disruption of normal islet clock performance compromises β-cell function and leads to loss of glycaemic control. Future work is warranted to further unravel the role of circadian clocks in human islet function in health and contributions to pathogenesis of T2DM.
Department of Physiology and Biomedical Engineering, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, USA.
K
K
Rakshit
Laboratory for Circadian and Sleep Medicine, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
J
J
Qian
Laboratory for Circadian and Sleep Medicine, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
C S
CS
Colwell
Department of Physiology and Biomedical Engineering, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, USA.
A V
AV
Matveyenko
D021081:Chronobiology Disorders / Q000150:complications; D057906:Circadian Clocks / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D005089:Exocytosis; D005247:Feeding Behavior / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000502:physiology*; D024821:Metabolic Syndrome / Q000209:etiology; D008928:Mitochondria / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology
D007328:Insulin; D005947:Glucose
T2DM; circadian clock; circadian disruption; insulin secretion; islet; β-cell