Postnatal ontogenesis of the islet circadian clock plays a contributory role in β-cell maturation process

Kuntol Rakshit, Jingyi Qian, Krutika Satish Gaonkar, Sangeeta Dhawan, Christopher S. Colwell, Aleksey V Matveyenko

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)911-922
Number of pages12
JournalDiabetes
Volume67
Issue number5
DOIs
StatePublished - May 1 2018

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Circadian Clocks
Insulin
Transcription Factors
Transgenic Rats
Gene Regulatory Networks
Cell- and Tissue-Based Therapy
Circadian Rhythm
Luciferases
Islets of Langerhans
Gene Expression
Glucose

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Postnatal ontogenesis of the islet circadian clock plays a contributory role in β-cell maturation process. / Rakshit, Kuntol; Qian, Jingyi; Gaonkar, Krutika Satish; Dhawan, Sangeeta; Colwell, Christopher S.; Matveyenko, Aleksey V.

In: Diabetes, Vol. 67, No. 5, 01.05.2018, p. 911-922.

Research output: Contribution to journalArticle

Rakshit, Kuntol ; Qian, Jingyi ; Gaonkar, Krutika Satish ; Dhawan, Sangeeta ; Colwell, Christopher S. ; Matveyenko, Aleksey V. / Postnatal ontogenesis of the islet circadian clock plays a contributory role in β-cell maturation process. In: Diabetes. 2018 ; Vol. 67, No. 5. pp. 911-922.
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