Role of the clock gene Rev-erbα in metabolism and in the endocrine pancreas.
Several hormones are regulated by circadian rhythms to adjust the metabolism to the light/dark cycles and feeding/activity patterns throughout the day. Circadian rhythms are mainly governed by the central clock located in the suprachiasmatic nucleus but also by clocks present in peripheral organs, like the endocrine pancreas. Plasma glucose levels and the main pancreatic hormones insulin and glucagon also exhibit daily variations. Alterations in circadian rhythms are associated with metabolic disturbances and pathologies such as obesity and diabetes. The molecular components of central and peripheral clocks and their regulatory mechanisms are well established. Among the different clock genes, Rev-erbα is considered one of the key links between circadian rhythms and metabolism. Rev-erbα is a critical part of a negative feedback loop in the core circadian clock and modulates the clock oscillatory properties. In addition, Rev-erbα plays an important role in the regulation of lipid and glucose metabolism, thermogenesis, adipocyte and muscle differentiation as well as mitochondrial function. In the endocrine pancreas, Rev-erbα regulates insulin and glucagon secretion and pancreatic β-cell proliferation. In the present review, we discuss all these subjects and, particularly, the role of the clock gene Rev-erbα in the endocrine pancreas.
Department of Cell Biology and Genetic, State University of Maringá, Maringá, Brazil.
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Vieira
CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) and Instituto de Bioingeniería, Universidad Miguel Hernandez, Elche, Spain.
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Merino
CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) and Instituto de Bioingeniería, Universidad Miguel Hernandez, Elche, Spain.
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Quesada
D017667:Adipocytes / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D057906:Circadian Clocks / Q000235:genetics*; D002940:Circadian Rhythm / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D025461:Feedback, Physiological; D005934:Glucagon / Q000378:metabolism; D050416:Glucagon-Secreting Cells / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics; D008928:Mitochondria / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000502:physiology*; D022722:Thermogenesis / Q000235:genetics
D001786:Blood Glucose; D007328:Insulin; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D005934:Glucagon
Rev-erbα; clock genes; glucose homeostasis; insulin and glucagon secretion; metabolism; type 2 diabetes