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Anchored phosphatases modulate glucose homeostasis
Author(s) -
Hinke Simon A,
Navedo Manuel F,
Ulman Allison,
Whiting Jennifer L,
Nygren Patrick J,
Tian Geng,
JimenezCaliani Antonio J,
Langeberg Lorene K,
Cirulli Vincenzo,
Tengholm Anders,
Dell'Acqua Mark L,
Santana L Fernando,
Scott John D
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2012.244
Subject(s) - biology , glucose homeostasis , homeostasis , phosphatase , phosphorylation , microbiology and biotechnology , endocrinology , diabetes mellitus , insulin resistance
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.