Molecular mechanisms involved in the simpatic activation of hepatic gluconeogenesis

Abstract

The understanding the mechanisms involved in the regulation of hepatic glucose production and, more specifically, in gluconeogenesis, is of great importance for pathophysiological understanding of different metabolic diseases and for the development of alternative treatments. Several studies have demonstrated that the cAMP responsive element binding protein (CREB) associated with its CREB transcriptional co-activator type 2 (CRTC2) plays a key role in the induction of the hepatic gluconeogenesis gene program in response to glucagon. However, little is known about the role of the Sympathetic Nervous System (SNS) in the modulation of this transcriptional complex and its resulting physiological effects. In recent experiments in our laboratory, it was found that the sympathetic innervation of the liver is capable of activating the gene expression and the activity of key enzymes of the gluconeogenesis in rodents exposed acutely to the cold. However, the molecular mechanisms involved in the answers are still unclear. The studies proposed here in are intended: (1) to continue the investigation of the physiological role of SNS in the adaptation to cold and in the activation of gluconeogenesis via CREB/CRTC2 in liver of mice submitted to chemical sympathectomy; (2) to study the hepatic adrenergic receptors involved in the stimulation of gluconeogenesis by norepinephrine; (3) clarify signaling pathways (PKA and PKC) can be involved in activation of CREB/CRTC2 by sympathetic system. (AU)