Role of AMP-activated protein kinase in the metabolic syndrome and in heart disease

Abstract 

Obesity, type 2 diabetes and the metabolic syndrome are disorders of energy balance, which the AMP-activated protein kinase (AMPK) regulates both at the cellular and whole body levels. AMPK switches cells from an anabolic state where nutrients are taken up and stored, to a catabolic state where they are oxidized. Drugs that activate AMPK indirectly (metformin and thiazolidinediones) are now the mainstay of treatment for type 2 diabetes, but more direct AMPK activators may have fewer side effects. However, activating mutations in AMPK can cause heart disease, and it will be important to look for adverse effects in the heart.

Abbreviations: ACC, acetyl-CoA carboxylase, AgRP, agouti-related peptide, AICAR, 5-aminoimidazole-4-carboxamide riboside, AMPK, AMP-activated protein kinase, AS160, Akt substrate of 160kDa, CaMKK, calmodulin-dependent protein kinase kinase, CBS1-4, cystathionine β-synthase motif 1-4, GLUT4, glucose transporter-4, IRS1, insulin receptor substrate-1, MC4, melanocortin-4, OCT1, organic cation transporter-1, PGC-1α, peroxisome proliferator-activated receptor-γ co-activator-1α, POMC, pro-opiomelanocortin, PPAR-γ, peroxisome proliferator-activated receptor-γ, TSC, tuberous sclerosis complex

Keywords: AMP-activated protein kinase, Metabolic syndrome, Diabetes, Metformin, Thiazolidinedione, Ventricular pre-excitation