Role of Nutrient and Energy Sensors in the Development of Type 2 Diabetes

Abstract

Cell survival depends on the constant challenge to match energy demands with nutrient availability. This process is mediated through a highly conserved network of metabolic fuel sensors that orchestrate both a cellular and whole-body energy balance. A mismatch between cellular energy demand and nutrient availability is a key factor in the development of type 2 diabetes, obesity, metabolic syndrome, and other associated pathologies; thus, understanding the fundamental mechanisms by which cells detect nutrient availability and energy demand may lead to the development of new treatments. This chapter reviews the role of the sensor PASK (protein kinase with PAS domain), analyzing its role in the mechanisms of adaptation to nutrient availability and the metabolic response in different organs (liver, hypothalamus) actively cooperating to control food intake, maintain glycaemia homeostasis, and prevent insulin resistance and weight gain.

Preventing Oxidative Stress in the Liver: An Opportunity for GLP-1 and/or PASK

“…Despite current efforts, the physiological regulators of PASK are still unknown. The PASK activation model proposes that the interaction of a metabolite with the PAS domain terminates its inhibitory function and transient activation occurs, which will subsequently be stabilized by auto or transphosphorylation and may activate/inhibit various substrates [ 55 , 58 , 60 , 61 ]. In mammals, PASK responds according to nutritional status by contributing to the regulation of glucose homeostasis, energy metabolism, and oxidative stress [ 62 , 63 , 64 , 65 ].…”