Anchored phosphatases modulate glucose homeostasis

作者：Hinke Simon A; Navedo Manuel F; Ulman Allison; Whiting Jennifer L; Nygren Patrick J; Tian Geng; Jimenez Caliani Antonio J; Langeberg Lorene K; Cirulli Vincenzo; Tengholm Anders; Dell' Acqua Mark L; Santana L Fernando; Scott John D^*

来源：The EMBO Journal, 2012, 31(20): 3991-4004.

DOI：10.1038/emboj.2012.244

• A-kinase anchoring protein (AKAP)
• calcineurin (PP2B)
• cyclic-AMP-dependent protein kinase (PKA)
• glucoregulation
• glucose-stimulated insulin secretion (GSIS)

Endocrine release of insulin principally controls glucose homeostasis. Nutrient-induced exocytosis of insulin granules from pancreatic beta-cells involves ion channels and mobilization of Ca2+ and cyclic AMP (cAMP) signalling pathways. Whole-animal physiology, islet studies and live-beta-cell imaging approaches reveal that ablation of the kinase/phosphatase anchoring protein AKAP150 impairs insulin secretion in mice. Loss of AKAP150 impacts L-type Ca2+ currents, and attenuates cytoplasmic accumulation of Ca2+ and cAMP in beta-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. The EMBO Journal (2012) 31, 3991-4004. doi:10.1038/emboj.2012.244; Published online 31 August 2012

• 出版日期2012-10-17