Effects of the POMC System on Glucose Homeostasis and Potential Therapeutic Targets for Obesity and Diabetes

Figures & data

Figure 1 Melanocortin system in glucose homeostasis. In the arcuate nucleus of the hypothalamus, there are many hormone receptors on pro-opiomelanocortin (POMC) neurons. Leptin, insulin, glucagon-like peptide (GLP)-1, and GLP-2 act on liver, skeletal muscle, and the pancreas to regulate blood glucose levels by binding with their corresponding receptors. At the same time, α-melanocyte stimulating hormone (α-MSH) on orexigenic or anorexigenic neurons binds with the melanocortin 4 receptor (MC4R) to regulate appetite and glucose homeostasis.

Figure 2 Leptin- and insulin-related signaling pathways in pro-opiomelanocortin (POMC) neurons. Leptin and insulin bind to their corresponding receptors and activate related signaling pathways, especially the phosphoinositide 3-kinase (PI3K) signaling pathway, which play important roles in glucose metabolism mediated by POMC neurons in the arcuate nucleus.

Abbreviations: (+), Positive regulatory factors; (-), Negative regulatory factors; IRS, insulin receptor substrate; JAK2, Janus tyrosine kinase 2; STAT3, signal transducer and activator of transcription 3; FoxO1, forkhead box protein O1; TRPC5, transient receptor potential channels-5; mTOR, mammalian target of rapamycin; S6K, S6 kinase; PLCγ1, phospholipase C-γ1; PDE3B, phosphodiesterase 3B; SHP2, Src homologous region protein tyrosine phosphatase 2; MAPK, mitogen-activated protein kinase; ERK1/2, extracellular signal-regulated kinase 1/2; AMPK, AMP-dependent kinase; ACC, acetyl-CoA carboxylase.

Figure 3 Toll-like receptor 4 (TLR4)-NF-κB pathway. Resistin can activate the TLR4-NF-κB pathway of pro-opiomelanocortin (POMC) neurons and inhibit expression of the insulin receptor, thereby regulating glucose homeostasis.

Figure 4 Pro-opiomelanocortin (POMC)-mediated regulation of glucagon-like peptide (GLP)-2 on glucose homeostasis. GLP-2 activates the phosphoinositide 3-kinase (PI3K)-AKT-forkhead box protein O1 (FOXO1) pathway by binding to the GLP-2 receptor expressed in POMC neurons. This reduces food intake and hepatic glucose production.