Anchored phosphatases modulate glucose homeostasis.
Enviado por Manuel F Navedo el
Título | Anchored phosphatases modulate glucose homeostasis. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Autores | Hinke, SA, Navedo, MF, Ulman, A, Whiting, JL, Nygren, PJ, Tian, G, Jimenez-Caliani, AJ, Langeberg, LK, Cirulli, V, Tengholm, A, Dell'acqua, ML, L Santana, F, Scott, JD |
Journal | EMBO J |
Volume | 31 |
Issue | 20 |
Pagination | 3991-4004 |
Date Published | 2012 Oct 17 |
ISSN | 1460-2075 |
Palabras clave | A Kinase Anchor Proteins, Amino Acid Motifs, Animals, Calcineurin, Calcium Signaling, Cyclic AMP, Glucose, Homeostasis, Insulin, Insulin resistance, Insulinoma, Islets of Langerhans, Liver, Male, Membrane Potentials, Membrane Proteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Models, Molecular, Muscle, Skeletal, Pancreatic Neoplasms, Phosphoprotein Phosphatases, Protein Interaction Mapping, Protein Kinases, Second Messenger Systems, Sequence Deletion, Tumor Cells, Cultured |
Abstract | Endocrine release of insulin principally controls glucose homeostasis. Nutrient-induced exocytosis of insulin granules from pancreatic β-cells involves ion channels and mobilization of Ca(2+) and cyclic AMP (cAMP) signalling pathways. Whole-animal physiology, islet studies and live-β-cell imaging approaches reveal that ablation of the kinase/phosphatase anchoring protein AKAP150 impairs insulin secretion in mice. Loss of AKAP150 impacts L-type Ca(2+) currents, and attenuates cytoplasmic accumulation of Ca(2+) and cAMP in β-cells. Yet surprisingly AKAP150 null animals display improved glucose handling and heightened insulin sensitivity in skeletal muscle. More refined analyses of AKAP150 knock-in mice unable to anchor protein kinase A or protein phosphatase 2B uncover an unexpected observation that tethering of phosphatases to a seven-residue sequence of the anchoring protein is the predominant molecular event underlying these metabolic phenotypes. Thus anchored signalling events that facilitate insulin secretion and glucose homeostasis may be set by AKAP150 associated phosphatase activity. |
DOI | 10.1038/emboj.2012.244 |
Alternate Journal | EMBO J. |
PubMed ID | 22940692 |
PubMed Central ID | PMC3474922 |
Grant List | DK54441 / DK / NIDDK NIH HHS / United States GM07750 / GM / NIGMS NIH HHS / United States GM48231 / GM / NIGMS NIH HHS / United States HL85686 / HL / NHLBI NIH HHS / United States HL85870 / HL / NHLBI NIH HHS / United States HL98200 / HL / NHLBI NIH HHS / United States NS048154 / NS / NINDS NIH HHS / United States NS40701 / NS / NINDS NIH HHS / United States R01 GM048231 / GM / NIGMS NIH HHS / United States R01 HL098200 / HL / NHLBI NIH HHS / United States R37 GM048231 / GM / NIGMS NIH HHS / United States / / Canadian Institutes of Health Research / Canada / / Howard Hughes Medical Institute / United States |