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Anchored phosphatases modulate glucose homeostasis.

The EMBO journal | Oct 17, 2012

http://www.ncbi.nlm.nih.gov/pubmed/22940692

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.

Pubmed ID: 22940692 RIS Download

Mesh terms: 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

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Associated grants

  • Agency: NIDDK NIH HHS, Id: DK54441
  • Agency: NIGMS NIH HHS, Id: GM07750
  • Agency: NIGMS NIH HHS, Id: GM48231
  • Agency: NHLBI NIH HHS, Id: HL85686
  • Agency: NHLBI NIH HHS, Id: HL85870
  • Agency: NHLBI NIH HHS, Id: HL98200
  • Agency: NINDS NIH HHS, Id: NS048154
  • Agency: NINDS NIH HHS, Id: NS40701
  • Agency: NIGMS NIH HHS, Id: R01 GM048231
  • Agency: NHLBI NIH HHS, Id: R01 HL098200
  • Agency: NINDS NIH HHS, Id: R01 NS040701
  • Agency: NIGMS NIH HHS, Id: R37 GM048231
  • Agency: Canadian Institutes of Health Research, Id:
  • Agency: Howard Hughes Medical Institute, Id:

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