title: All-encomPASsing regulation of β-cells: PAS domain proteins in β-cell dysfunction and diabetes.
abstract: As a sensory micro-organ, pancreatic β-cells continually respond to nutritional signals and neuroendocrine input from other glucoregulatory organs. This sensory ability is essential for normal β-cell function and systemic glucose homeostasis. Period circadian protein (Per)-aryl hydrocarbon receptor nuclear translocator protein (Arnt)-single-minded protein (Sim) (PAS) domain proteins have a conserved role as sensory proteins, critical in adaptation to changes in voltage, oxygen potential, and xenobiotics. Within β-cells, PAS domain proteins such as hypoxia inducible factor 1α (Hif1α), Arnt, PAS kinase, Bmal1, and Clock respond to disparate stimuli, but act in concert to maintain proper β-cell function. Elucidating the function of these factors in islets offers a unique insight into the sensing capacity of β-cells, the consequences of impaired sensory function, and the potential to develop novel therapeutic targets for preserving β-cell function in diabetes.
authors.affiliation: Diabetes Research Group, Child and Family Research Institute, Vancouver, British Columbia, Canada; The Departments of Surgery and Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, V5Z 4H4 Canada. Electronic address: psabatini@cfri.ca.
authors.forename: Paul V
authors.initials: PV
authors.lastname: Sabatini
authors.affiliation: Diabetes Research Group, Child and Family Research Institute, Vancouver, British Columbia, Canada; The Departments of Surgery and Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, V5Z 4H4 Canada. Electronic address: francis.lynn@ubc.ca.
authors.forename: Francis C
authors.initials: FC
authors.lastname: Lynn
mesh_terms: D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000737:chemistry / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins / Q000737:chemistry / Q000502:physiology; D003920:Diabetes Mellitus / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D029721:Drosophila Proteins / Q000737:chemistry / Q000502:physiology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000737:chemistry / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000473:pathology* / Q000502:physiology*; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology; D056950:Period Circadian Proteins / Q000737:chemistry / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000502:physiology; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000737:chemistry* / Q000502:physiology*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000737:chemistry / Q000502:physiology
chemical_list: D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D029721:Drosophila Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D017346:Protein Serine-Threonine Kinases; D014157:Transcription Factors; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497442:HIF1A protein, human; C089449:sim protein, Drosophila; C116037:PAS domain kinases
keywords: Arnt; Bmal1; Clock; Hif1α; Npas4; PAS domain; Pask; Per; Sim; Vhl; circadian; diabetes; hypoxia; insulin secretion; β-cells