Postnatal Ontogenesis of the Islet Circadian Clock Plays a Contributory Role in β-Cell Maturation Process
| Autor: | Krutika S. Gaonkar, Sangeeta Dhawan, Kuntol Rakshit, Jingyi Qian, Aleksey V. Matveyenko, Christopher S. Colwell |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Endocrinology Diabetes and Metabolism Circadian clock Wistar CLOCK Proteins Cell Maturation Medical and Health Sciences Animals Genetically Modified Rats Sprague-Dawley Mice Insulin-Secreting Cells 2.1 Biological and endogenous factors Aetiology Pediatric Mice Knockout geography.geographical_feature_category Diabetes ARNTL Transcription Factors Cell Differentiation Period Circadian Proteins Islet Circadian Rhythm Cell biology Female Sleep Research PER1 endocrine system Knockout 1.1 Normal biological development and functioning Period (gene) Transgene Genetically Modified Biology Endocrinology & Metabolism Islets of Langerhans 03 medical and health sciences Underpinning research Circadian Clocks Genetics Internal Medicine Animals Circadian rhythm Rats Wistar Transcription factor Metabolic and endocrine geography Newborn Rats 030104 developmental biology Islet Studies Animals Newborn Sprague-Dawley |
| Zdroj: | Diabetes, vol 67, iss 5 |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | Development of cell replacement therapies in diabetes requires understanding of the molecular underpinnings of β-cell maturation. The circadian clock regulates diverse cellular functions important for regulation of β-cell function and turnover. However, postnatal ontogenesis of the islet circadian clock and its potential role in β-cell maturation remain unknown. To address this, we studied wild-type Sprague-Dawley as well as Period1 luciferase transgenic (Per1:LUC) rats to determine circadian clock function, clock protein expression, and diurnal insulin secretion during islet development and maturation process. We additionally studied β-cell–specific Bmal1-deficient mice to elucidate a potential role of this key circadian transcription factor in β-cell functional and transcriptional maturation. We report that emergence of the islet circadian clock 1) occurs during the early postnatal period, 2) depends on the establishment of global behavioral circadian rhythms, and 3) leads to the induction of diurnal insulin secretion and gene expression. Islet cell maturation was also characterized by induction in the expression of circadian transcription factor BMAL1, deletion of which altered postnatal development of glucose-stimulated insulin secretion and the associated transcriptional network. Postnatal development of the islet circadian clock contributes to early-life β-cell maturation and should be considered for optimal design of future β-cell replacement strategies in diabetes. |
| Databáze: | OpenAIRE |
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