Glucose homeostasis and p75NTR

The p75 neurotrophin receptor (p75), a member of the tumor necrosis factor receptor (TNFR) superfamily, was originally identified as a receptor for neurotrophins and is expressed in the nervous system and in many non-neuronal tissues such as white adipose tissue (WAT), skeletal muscle and liver. Although the biological functions of p75 in the nervous system have been extensively studied, the multiple roles of p75 in non-neuronal tissues are currently emerging. Recent studies have shown surprisingly diverse biologic functions for p75, including liver and muscle regeneration, extracellular matrix remodeling and angiogenesis in response to hypoxia. Since p75 lacks a catalytic motif, the diversity of its biological functions is attributed to the large number of intracellular adaptor proteins that interact with the intracellular domain of p75 (p75) and, in turn, activate multiple signaling pathways. We reported an unexpected function of p75 in the regulation of glucose metabolism, whereby p75 controls insulin-stimulated glucose transport and insulin sensitivity. Whole-body glucose metabolism is regulated by a complex communication network involving the adipose tissue, skeletal muscle, liver, pancreas and brain. In normal conditions, these tissues rapidly maintain glucose levels after caloric ingestion or long-term starvation. However, insulin resistance, a key feature of type-2 diabetes, reduces the ability to maintain normal glucose homeostasis, causing decreased glucose disposal and increased hepatic glucose production. We showed that genetic loss of p75 lowered glycemic excursions after glucose, increased the hypoglycemic Glucose homeostasis and p75NTR The sweet side of neurotrophin receptor signaling