The ventromedial hypothalamic nucleus watchdog of whole-body glucose homeostasis

Authors: TU, LONGLONG - Children'S Nutrition Research Center (CNRC); FUKUDA, MAKOTO - Children'S Nutrition Research Center (CNRC); TONG, QINGCHUN - University Of Texas Health Science Center; XU, YONG - Children'S Nutrition Research Center (CNRC)

Submitted to: Cell & Bioscience
Publication Type: Review Article
Publication Acceptance Date: 4/25/2022
Publication Date: 5/26/2022
Citation: Tu, L., Fukuda, M., Tong, Q., Xu, Y. 2022. The ventromedial hypothalamic nucleus watchdog of whole-body glucose homeostasis. Cell & Bioscience. 12. Article 71. https://doi.org/10.1186/s13578-022-00799-2.
DOI: https://doi.org/10.1186/s13578-022-00799-2

Interpretive Summary: This review focuses on the role of the brain, particularly the ventromedial hypothalamic nucleus (VMH), in glucose sensing and glucose homeostasis in the body. The authors discuss the mechanisms by which the brain detects and responds to changes in glucose levels, including the potential roles of non-neuronal cells and extracellular matrix. They also review the ionic mechanisms by which glucose-sensing neurons sense fluctuations in glucose levels and discuss the implications of heterogeneous neurons in the VMH, including sex differences. The authors identify research gaps and highlight the need for further mechanistic studies in the future.

Technical Abstract: The brain, particularly the ventromedial hypothalamic nucleus (VMH), has been long known for its involvement in glucose sensing and whole-body glucose homeostasis. However, it is still not fully understood how the brain detects and responds to the changes in the circulating glucose levels, as well as brain-body coordinated control of glucose homeostasis. In this review, we address the growing evidence implicating the brain in glucose homeostasis, especially in the contexts of hypoglycemia and diabetes. In addition to neurons, we emphasize the potential roles played by non-neuronal cells, as well as extracellular matrix in the hypothalamus in whole-body glucose homeostasis. Further, we review the ionic mechanisms by which glucose-sensing neurons sense fluctuations of ambient glucose levels. We also introduce the significant implications of heterogeneous neurons in the VMH upon glucose sensing and whole-body glucose homeostasis, in which sex difference is also addressed. Meanwhile, research gaps have also been identified, which necessities further mechanistic studies in future.