Nocturnal Brain Activity Regulates Blood Sugar Levels during the Night
In a groundbreaking study, a team of researchers at the Caswell Diabetes Institute, University of Michigan, have discovered a crucial role of specific neurons in the hypothalamus in regulating blood sugar levels during normal activities. This research, published in the prestigious journal Science, sheds light on the neuronal control of metabolism, specifically the roles played by the brain and nervous system in metabolic control and disease.
The research involved chronic silencing and acute optogenetic activation of neurons in the ventromedial nucleus of the hypothalamus that express the cholecystokinin b receptor (VMH neurons). The team found that these neurons support glucose homeostasis during short fasts and contribute to gluconeogenic substrate mobilization and lipolysis.
Acute activation of VMH neurons was found to mobilize additional gluconeogenic substrates beyond glycerol. Interestingly, restoring glycerol availability following VMH neuron silencing restores glucose levels. This suggests that VMH neurons mobilize glucose without depleting hepatic glycogen or increasing gluconeogenic gene expression, but instead mobilize glycerol in a β3-adrenergic receptor (β3-AR)-dependent manner.
The study also revealed the presence of different glucose-mobilizing neuronal populations that engage distinct mechanisms in a context-dependent manner. This finding provides the brain with flexibility to coordinate the appropriate glycemic response to different circumstances.
The authors of the research include Jiaao Su, Abdullah Hashsham, Nandan Kodur, Carla Burton, Amanda Mancuso, Anjan Singer, Jennifer Wloszek, Abigail J. Tomlinson, Warren T. Yacawych, Jonathan N. Flak, Kenneth T. Lewis, Lily R. Oles, Hiroyuki Mori, Nadejda Bozadjieva-Kramer, Adina F. Turcu, Ormond A. MacDougald, and Martin G. Myers. It's worth noting that some of the authors have reported relationships with various pharmaceutical companies.
The research was supported by several grants and foundations, including the Michigan Diabetes Research Center, the Mouse Metabolic Phenotyping Center - Live, the Michigan Nutrition and Obesity Center Adipose Tissue Core, the Department of Veterans Affairs, the Warren Alpert Foundation, Endocrine Fellows Foundation, Marilyn H. Vincent Foundation, Novo Nordisk, and NIH grant K08 DK1297226.
This study provides valuable insights into the neuronal control of metabolism and could lead to new strategies for managing metabolic diseases such as diabetes. Further research is needed to fully understand the complex interplay between neurons and metabolism.
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