A glucose-sensing mechanism with glucose transporter 1 and pyruvate kinase in the area postrema regulates hepatic glucose production in rats

Li, Rosa J.W.; Chiu, Jennifer F M; Bruce, Kyla; Zhang, Songyang; Barros, Daniel R.; Yue, Jessica T.Y.; Lam, Tony K.T.

doi:10.1016/j.jbc.2023.104633

Journal of Biological Chemistry

2023

DOI: 10.1016/j.jbc.2023.104633

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A glucose-sensing mechanism with glucose transporter 1 and pyruvate kinase in the area postrema regulates hepatic glucose production in rats

Rosa J.W. Li¹,

Jennifer F M Chiu²,

Kyla Bruce³

et al.

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Cited by 2 publications

References 27 publications

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Acute Activation of GFRAL in the Area Postrema Contributes to Glucose Regulation Independent of Weight

Zhang,

Danaei,

Bruce

et al. 2023

Diabetes

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GDF15 regulates energy balance and glucose homeostasis in rodents by activating its receptor GFRAL expressed in the area postrema of the brain. However, whether GDF15-GFRAL signaling in the area postrema regulates glucose tolerance independent of changes in food intake and weight and contributes to the glucose-lowering effect of metformin remain unknown. Herein, we report that direct acute GDF15 infusion into the area postrema of high fat fed rats increased intravenous glucose tolerance and insulin sensitivity to lower hepatic glucose production independent of changes in food intake, weight, and plasma insulin levels under conscious, unrestrained, and non-stressed conditions. In parallel, metformin infusion concurrently increased plasma GDF15 levels and glucose tolerance. Finally, a knockdown of GFRAL expression in the area postrema not only negated administration of GDF15 but also metformin to increase glucose tolerance independent of changes in food intake, weight, and plasma insulin levels. In summary, activation of GFRAL in the area postrema contributes to glucose regulation of GDF15 and metformin in vivo.

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Acute Activation of GFRAL in the Area Postrema Contributes to Glucose Regulation Independent of Weight

Zhang,

Danaei,

Bruce

et al. 2023

Diabetes

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Regulation of Energy and Glucose Homeostasis by the Nucleus of the Solitary Tract and the Area Postrema

Bruce,

Garrido,

Zhang

et al. 2024

Endocrinol Metab

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The central nervous system regulates feeding, weight and glucose homeostasis in rodents and humans, but the site-specific mechanisms remain unclear. The dorsal vagal complex in the brainstem that contains the nucleus of the solitary tract (NTS) and area postrema (AP) emerges as a regulatory center that impacts energy and glucose balance by monitoring hormonal and nutrient changes. However, the specific mechanistic metabolic roles of the NTS and AP remain elusive. This mini-review highlights methods to study their distinct roles and recent findings on their metabolic differences and similarities of growth differentiation factor 15 (GDF15) action and glucose sensing in the NTS and AP. In summary, future research aims to characterize hormonal and glucose sensing mechanisms in the AP and/or NTS carries potential to unveil novel targets that lower weight and glucose levels in obesity and diabetes.

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A glucose-sensing mechanism with glucose transporter 1 and pyruvate kinase in the area postrema regulates hepatic glucose production in rats

Cited by 2 publications

References 27 publications

Acute Activation of GFRAL in the Area Postrema Contributes to Glucose Regulation Independent of Weight

Acute Activation of GFRAL in the Area Postrema Contributes to Glucose Regulation Independent of Weight

Regulation of Energy and Glucose Homeostasis by the Nucleus of the Solitary Tract and the Area Postrema

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