title: Insulin and β Adrenergic Receptor Signaling: Crosstalk in Heart.
abstract: Recent advances show that insulin may affect β adrenergic receptor (βAR) signaling in the heart to modulate cardiac function in clinically relevant states, such as diabetes mellitus (DM) and heart failure (HF). Conversely, activation of βAR regulates cardiac glucose uptake and promotes insulin resistance (IR) in HF. Here, we discuss the recent characterization of the interaction between the cardiac insulin receptor (InsR) and βAR in the myocardium, in which insulin stimulation crosstalks with cardiac βAR via InsR substrate (IRS)-dependent and G-protein receptor kinase 2 (GRK2)-mediated phosphorylation of β2AR. The insulin-induced phosphorylation promotes β2AR coupling to Giand expression of phosphodiesterase 4D, which both inhibit cardiac adrenergic signaling and compromise cardiac contractile function. These recent developments could support new approaches for the effective prevention or treatment of obesity- or DM-related HF.
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Huazhong University of Science and Technology, Wuhan, China. Electronic address: fuqin@mails.tjmu.edu.cn.
authors.forename: Qin
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Anhui Medical University, Hefei, China. Electronic address: hfwqt727@163.com.
authors.forename: Qingtong
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, University of California, Davis, CA, USA; VA Northern California Health Care System, Mather, CA, USA. Electronic address: ykxiang@ucdavis.edu.
authors.forename: Yang K
authors.initials: YK
authors.lastname: Xiang
mesh_terms: D000818:Animals; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D007328:Insulin; D011943:Receptors, Adrenergic, beta; D018343:Receptors, Adrenergic, beta-2; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4