Article

AMP-activated protein kinase in metabolic control and insulin signaling

Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee, Scotland, UK.
Circulation Research (Impact Factor: 11.09). 03/2007; 100(3):328-41. DOI: 10.1161/01.RES.0000256090.42690.05
Source: PubMed

ABSTRACT The AMP-activated protein kinase (AMPK) system acts as a sensor of cellular energy status that is conserved in all eukaryotic cells. It is activated by increases in the cellular AMP:ATP ratio caused by metabolic stresses that either interfere with ATP production (eg, deprivation for glucose or oxygen) or that accelerate ATP consumption (eg, muscle contraction). Activation in response to increases in AMP involves phosphorylation by an upstream kinase, the tumor suppressor LKB1. In certain cells (eg, neurones, endothelial cells, and lymphocytes), AMPK can also be activated by a Ca(2+)-dependent and AMP-independent process involving phosphorylation by an alternate upstream kinase, CaMKKbeta. Once activated, AMPK switches on catabolic pathways that generate ATP, while switching off ATP-consuming processes such as biosynthesis and cell growth and proliferation. The AMPK complex contains 3 subunits, with the alpha subunit being catalytic, the beta subunit containing a glycogen-sensing domain, and the gamma subunits containing 2 regulatory sites that bind the activating and inhibitory nucleotides AMP and ATP. Although it may have evolved to respond to metabolic stress at the cellular level, hormones and cytokines such as insulin, leptin, and adiponectin can interact with the system, and it now appears to play a key role in maintaining energy balance at the whole body level. The AMPK system may be partly responsible for the health benefits of exercise and is the target for the antidiabetic drug metformin. It is a key player in the development of new treatments for obesity, type 2 diabetes, and the metabolic syndrome.

2 Followers
 · 
150 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Diabetes mellitus (DM) is managed by insulin (type-I diabetes) and oral hypoglycemics (type-II diabetes). Oral hypoglycemics prevent T cell proliferation. It was hypothesiszed that oral hypoglycemics decreases number of T cells. A cross sectional study was undertaken to determine frequency of T cells in DM patients being treated with oral hypoglycemics and with insulin. Study included 80 subjects and their blood sample was analyzed for T cells by four color FACS caliber, using fluorescein isothiocyanate 139 tagged monoclonal antibodies against CD3 and PerCP against CD45. Mean±SD of T cell percentage of patients on oral hypoglycemics was high (61.11±8.68 %) compared to insulin therapy (60.80±11.91 %). On comparison there was no statistically significant difference. No significant difference in percentage of T cells but significant difference was observed in age, BMI, systolic and diastolic BP of DM patients on oral hypoglycemics and insulin therapy.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: AMP-activated protein kinase (AMPK) is a heterotrimeric serine/threonine protein kinase that is activated by cellular perturbations associated with ATP depletion or stress. While AMPK modulates the activity of a variety of targets containing a specific phosphorylation consensus sequence, the number of AMPK targets and their influence over cellular processes is currently thought to be limited. We queried the human and the mouse proteomes for proteins containing AMPK phosphorylation consensus sequences. Integration of this database into Gaggle software facilitated the construction of probable AMPK-regulated networks based on known and predicted molecular associations. In vitro kinase assays were conducted for preliminary validation of 12 novel AMPK targets across a variety of cellular functional categories, including transcription, translation, cell migration, protein transport, and energy homeostasis. Following initial validation, pathways that include NAD synthetase 1 (NADSYN1) and protein kinase B (AKT2) were hypothesized and experimentally tested to provide a mechanistic basis for AMPK regulation of cell migration and maintenance of cellular NAD(+) concentrations during catabolic processes. This study delineates an approach that encompasses both in silico procedures and in vitro experiments to produce testable hypotheses for AMPK regulation of cellular processes.
    BMC Systems Biology 12/2015; 9(1):156. DOI:10.1186/s12918-015-0156-0 · 2.85 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this study, we investigated whether tetracosanol, an aliphatic alcohol isolated from Saccharum sinense, enhances insulin receptor kinase activity to exhibit an insulin synergistic effect in vitro and in vivo. The insulin plus tetracosanol enhanced insulin receptor kinase showed that AKT activity was down-regulated by S961 in differentiated L6 myotubes. Meanwhile, insulin plus tetracosanol restored the ability of glucose transporter translocation and glucose uptake in differentiated myotubes with S961-induced insulin resistance in vitro. The modification of carbon chain lengths and the hydroxyl group of tetracosanol showed that it served as a critical chemical structure for the glucostasis effect in vivo. This study provides new evidence to show that tetracosanol can improve glycaemic control via insulin receptor kinase activity induced and leads to the enhancement of glucose transporter translocation to improve glucose uptake. The hydroxyl group of tetracosanol plays a critical role for insulin receptor kinase activity.
    Journal of Functional Foods 04/2015; 14. DOI:10.1016/j.jff.2015.01.033 · 4.48 Impact Factor

Preview

Download
3 Downloads

Mhairi Towler