EMAIL THIS PAGE TO A FRIEND

Scientific reports

Acetylation of glucokinase regulatory protein decreases glucose metabolism by suppressing glucokinase activity.


PMID 26620281

Abstract

Glucokinase (GK), mainly expressed in the liver and pancreatic β-cells, is critical for maintaining glucose homeostasis. GK expression and kinase activity, respectively, are both modulated at the transcriptional and post-translational levels. Post-translationally, GK is regulated by binding the glucokinase regulatory protein (GKRP), resulting in GK retention in the nucleus and its inability to participate in cytosolic glycolysis. Although hepatic GKRP is known to be regulated by allosteric mechanisms, the precise details of modulation of GKRP activity, by post-translational modification, are not well known. Here, we demonstrate that GKRP is acetylated at Lys5 by the acetyltransferase p300. Acetylated GKRP is resistant to degradation by the ubiquitin-dependent proteasome pathway, suggesting that acetylation increases GKRP stability and binding to GK, further inhibiting GK nuclear export. Deacetylation of GKRP is effected by the NAD(+)-dependent, class III histone deacetylase SIRT2, which is inhibited by nicotinamide. Moreover, the livers of db/db obese, diabetic mice also show elevated GKRP acetylation, suggesting a broader, critical role in regulating blood glucose. Given that acetylated GKRP may affiliate with type-2 diabetes mellitus (T2DM), understanding the mechanism of GKRP acetylation in the liver could reveal novel targets within the GK-GKRP pathway, for treating T2DM and other metabolic pathologies.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

D8375
2-Deoxy-D-glucose, ≥98% (GC), crystalline
C6H12O5
D6134
2-Deoxy-D-glucose, ≥99% (GC), crystalline
C6H12O5
D3179
2-Deoxy-D-glucose, BioXtra, ≥98%
C6H12O5
271004
Acetonitrile, anhydrous, 99.8%
C2H3N
675415
Acetonitrile, HPLC Plus, ≥99.9%, poly-coated bottles
C2H3N
437557
Acetonitrile, ≥99.5%, ACS reagent
C2H3N
270717
Acetonitrile, HPLC grade, ≥99.93%
C2H3N
L010000-HH
Acetonitrile, for DNA synthesis
C2H3N
01-0650
Acetonitrile, ≥99.8%, for HPLC
C2H3N
01-0623
Acetonitrile, for residue analysis, JIS 5000
C2H3N
01-0645
Acetonitrile, for chromatography
C2H3N
733466
Acetonitrile, electronic grade, 99.999% trace metals basis
C2H3N
L110001
Acetonitrile
C2H3N
L011800
Acetonitrile
C2H3N
576956
Acetonitrile solution, contains 0.1 % (v/v) formic acid, for HPLC
C2H3N
574732
Acetonitrile solution, contains 0.1 % (v/v) trifluoroacetic acid, for HPLC
C2H3N
574724
Acetonitrile solution, contains 0.05 % (v/v) trifluoroacetic acid
C2H3N
679186
Acetonitrile solution, contains 5 % (v/v) water, 0.05 % (w/v) ammonium formate, 0.1 % (v/v) formic acid, for HPLC
C2H3N
685461
Acetonitrile solution, contains 10.0% acetone, 40.0% 2-propanol, 0.05% formic acid
C2H3N
703664
Acetonitrile solution, NMR reference standard, 0.23 wt. % in D2O (99.9 atom % D), water 0.05 wt. %, NMR tube size 6.5 mm × 8 in.
C2H3N
A6141
Ammonium bicarbonate, ReagentPlus®, ≥99.0%
CH5NO3
D8284
Bicinchoninic acid disodium salt hydrate, ≥98% (HPLC)
C20H10N2Na2O4 · xH2O
SML0002
C646, ≥98% (HPLC)
C24H19N3O6
01810
Cycloheximide, ≥93.0% (HPLC)
C15H23NO4
C7698
Cycloheximide, from microbial, ≥94% (TLC)
C15H23NO4
C1988
Cycloheximide, Biotechnology Performance Certified
C15H23NO4
C4859
Cycloheximide solution, Ready-Made Solution, microbial, 100 mg/mL in DMSO, 0.2 μm filtered
C15H23NO4
11020
DL-Arginine, ≥97.0% (NT)
C6H14N4O2
EDS
Ethylenediaminetetraacetic acid, BioUltra, anhydrous, ≥99% (titration)
C10H16N2O8
E6758
Ethylenediaminetetraacetic acid, anhydrous, crystalline, BioReagent, suitable for cell culture
C10H16N2O8