Jet-laggedpancreatic β-cells predispose a person to diabetes – Causal relationship between circadian rhythms and diabetes.What’s the underlying mechanism?

A research group led by Associate Professor Yasuharu Ohta, Assistant Professor Akihiko Taguchi and Professor Yukio Tanizawa has reported that a decrease in the signal from the clock gene network induces impaired insulin secretion.

Various Lifestyles related to circadian dysruption, including shift work and sleep disturbances, contribute to glucose intolerance. Our study partly clarified the molecular mechanisms linking circadian dysruption and glucose intolerance, which leads to new therapeutic cocept of type2 diabetes.

This research achievement was published online in the scientific journal EbioMedicine on March 30, 2017. EbioMedicine is an open access journal that is published in collaboration with Cell Press and The Lancet.

 

[Overview of research results] 

Wolfram syndrome is caused by the WFS1 mutation and characterized by severe diabetes mellitus. In this study , we found that DBP activity was obviously suppressed in the pancreatic β-cells (insulin producing cells) of WFS1-deficient mice DBP is the transcription factor (note 1) that participates in the regulation of clock outputs

We created genetically modified mice in which DBP activity was supposed to be  suppressed in pancreatic β-cells tissue-specifically, and these mice developed severe glucose intolerance accompanied by significantly impaired insulin secretion. Digestion/absorption systems prepare for the ingestion of breakfast based on the local time. At the same time, pancreatic β-cells probably prepare to secrete insulin. Our findings suggest that DBP transcriptional activity is an essential component of preparing β-cells to release insulin. Most of us are fully aware of circadina rhytm through “jet lag”. Our findings suggest that jet-lagged β-cells cannot secrete insulin, predisposing person a person to diabetes.

Active time* This research was supported by grants from the Japan Society for the Promotion of Science.