A potential role for mTORC1/2 in Î²2 adrenergic regulation of skeletal muscle glucose oxidation in models of intrauterine growth restriction.
Robert Posont, Caitlin Cadaret, Taylor Barnes, Dustin Yates
The epidemic of intrauterine growth restriction (IUGR) continues to be a leading cause of perinatal morbidity and mortality throughout the world. This condition has been linked to the development of metabolic health problems such as obesity, hypertension, glucose intolerance, and type 2 diabetes at all ages. Previous studies have demonstrated that IUGR fetal adaptations impair proper glucose homeostasis in part via changes in insulin responsiveness in key tissues including skeletal muscle and liver, and that these deficits persists into adulthood. Many components of insulin signaling pathways associated with glucose metabolic regulation have been evaluated in IUGR tissues for adaptive changes. Among these are mammalian target of rapamycin complexes 1 and 2 (mTORC1/2) and their associated pathways, which function in mitochondrial control and maintenance. However, recent findings demonstrate that Î²2 adrenoceptors (Î²2AR) appear to activate an insulin-independent pathway or pathways that modify glucose metabolism via mTORC1/2 complexes. These findings represent a novel potential target for interventions that could improve the treatment and prevention of IUGR-induced metabolic disorders. This review will focus on mechanistic components of Î²2AR-mTORC1/2 signaling as well as their role in regulating glucose oxidative metabolism within skeletal muscle.