Circadian rhythm regulation mechanism of insulin sensitivity

Ding Guolian's research group from the Obstetrics and Gynecology Hospital of Fudan University/Reproductive and Development Research Institute cooperated with Sun Zheng's research team of Baylor College of Medicine and Chen Li's research group of Qilu Hospital of Shandong University to discover the GABA nerve in the suprachiasmatic nucleus (SCN) area of ​​the hypothalamus The meta-REV-ERB gene controls insulin to inhibit the circadian rhythm of liver gluconeogenesis, which is of great significance for in-depth understanding of the timing and air conditioning control of peripheral glucose metabolism in the central nervous system, and will also help guide blood glucose control strategies for diabetic patients.

As early as decades ago, scientists in mice and humans have found that insulin sensitivity in glucose metabolism has a circadian rhythm.

It is these two mechanisms that restrict each other, along with fluctuations in insulin levels, maintain the stability of blood sugar throughout the day.

According to reports, the GABA neurons in the SCN area of ​​the hypothalamus (SCNGABA) are enriched with members of the nuclear receptor family REV-ERB-α and REV-ERB-β, which are also drug targets in the molecular biological clock.

In this study, glucose clamp analysis showed that wild-type (WT) mice had significant levels of systemic insulin sensitivity, insulin sensitivity to inhibit glycogen production, and the background level of liver sugar production.

"This phenomenon is not affected by eating and exercise behavior.

More interestingly, the researchers induced the rhythmic expression of exogenous REV-ERB in SCNGABA neurons in KO mice.

It has also been clinically found that among diabetic patients, a "dawn phenomenon" occurs in some patients.

In the above experiment, KO mice only showed abnormal glucose metabolism when they were awakened, suggesting that the circadian clock disturbance may cause the dawn phenomenon.

“Diabetes patients presenting hyperglycemia at dawn, especially after breakfast, are associated with abnormal expression rhythms of REV-ERB-α and REV-ERB-β.

Related paper information: org/10.