SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes.

Pancreatic β-cell dysfunction is a key feature of type 2 diabetes, and novel regulators of insulin secretion are desirable. Here we report that the succinate receptor (SUCNR1) is expressed in β-cells and is up-regulated in hyperglycemic states in mice and humans. We found that succinate acts as a hormone-like metabolite and stimulates insulin secretion via a SUCNR1-Gq-PKC-dependent mechanism in human β-cells.

SUCNR1 signaling in adipocytes controls energy metabolism by modulating circadian clock and leptin expression.

Adipose tissue modulates energy homeostasis by secreting leptin, but little is known about the factors governing leptin production. We show that succinate, long perceived as a mediator of immune response and lipolysis, controls leptin expression via its receptor SUCNR1. Adipocyte-specific deletion of Sucnr1 influences metabolic health according to nutritional status.

Soluble factors influencing the neural stem cell niche in brain physiology, inflammation, and aging.

Within the adult central nervous system (CNS) of most mammals resides a resident stem cell population, known as neural stem cells (NSCs). NSCs are located within specific niches of the CNS and maintain a self-renewal and proliferative capacity to generate new neurons, astrocytes, and oligodendrocytes throughout adulthood. The NSC niches are dynamic and active environments that are within proximity to the systemic circulation and the cerebrospinal fluid (CSF).