title: Targeting cAMP/PKA pathway for glycemic control and type 2 diabetes therapy.
abstract: In mammals, cyclic adenosine monophosphate (cAMP) is an intracellular second messenger that is usually elicited by binding of hormones and neurotransmitters to G protein-coupled receptors (GPCRs). cAMP exerts many of its physiological effects by activating cAMP-dependent protein kinase (PKA), which in turn phosphorylates and regulates the functions of downstream protein targets including ion channels, enzymes, and transcription factors. cAMP/PKA signaling pathway regulates glucose homeostasis at multiple levels including insulin and glucagon secretion, glucose uptake, glycogen synthesis and breakdown, gluconeogenesis, and neural control of glucose homeostasis. This review summarizes recent genetic and pharmacological studies concerning the regulation of glucose homeostasis by cAMP/PKA in pancreas, liver, skeletal muscle, adipose tissues, and brain. We also discuss the strategies for targeting cAMP/PKA pathway for research and potential therapeutic treatment of type 2 diabetes mellitus (T2D).
authors.affiliation: Division of EndocrinologyZhengzhou Children's Hospital, Zhengzhou, Henan, China yhhua415@163.com linghai@uw.edu.
authors.forename: Haihua
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of PharmacologyUniversity of Washington, Seattle, Washington, USA yhhua415@163.com linghai@uw.edu.
authors.forename: Linghai
authors.initials: L
authors.lastname: Yang
mesh_terms: D000818:Animals; D001786:Blood Glucose; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000628:therapy*; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D058990:Molecular Targeted Therapy; D018482:Muscle, Skeletal / Q000378:metabolism; D009928:Organ Specificity; D015398:Signal Transduction
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose
keywords: PKA; diabetes; glucagon; glucose; insulin