Project title
Nocturnin 基因在胰島細胞功能的角色與其分子機制的研究 (III)
Internal ID
MOST102-2314-B002-022-MY3
Principal Investigator
Start Date
August 1, 2015
End Date
July 31, 2016
Investigators
Organizations
Partner Organizations
Study the Role of Nocturnin on Islet Cell Function and Its Molecular Mechanism (III) = Nocturnin 基因在胰島細胞功能的角色與其分子機制的研究 (III)
Keywords
Nocturnin
circadian rhythm
islet beta cell function
islet beta cell survival
Description
The contribution of the circadian system in regulating metabolism has received increasing attention over recent years. Many metabolic processes exhibit coordinated circadian oscillation, such as feeding behavior and the metabolism of glucose and lipids, and many genes involved in metabolic control are rhythmically expressed. Pancreatic islets possess self-sustained circadian gene and protein oscillations of the transcription factors CLOCK and BMAL1. The phase of oscillation of islet genes involved in growth, glucose metabolism and insulin signaling is delayed in circadian mutant mice, and both CLOCK and BMAL1 mutants show impaired glucose tolerance, reduced insulin secretion and defects in size and proliferation of pancreatic islets that worsen with age. A peripheral clock output gene, a circadian deadenylase, Nocturnin (NOC) knockout mice confers resistance to hepatic steatosis and diet-induced obesity. To further addressing molecular mechanisms of Noc on various metabolic phenotypes related to insulin secretion and insulin resistance, we have generated conventional knockout mice of the NOC gene and the mice have been crossed to B6 (C57BL/6 J) to near congenic strain (crossed at 10 generations). We also have some preliminary data to demonstrate the impaired glucose-stimulated insulin secretion in NOC(-/-) mice and identified some differentially expressed genes and microRNA in NOC(-/-) mice islets, and need further validation and investigation of the molecular mechanism of Noc gene on islet cell function and beta cell survival. Furthermore, we will also generate islet beta cell specific deletion of NOC mice to further dissect the role of Noc on islet functions and beta cell survival.