Dataset Information

Tankyrase modulates insulin sensitivity in skeletal muscle cells by regulating stability of GLUT4 vesicle proteins

ABSTRACT: Tankyrase1 and 2, members of the poly(ADP-ribose) polymerase family, play a role in multiple biological processes including Wnt signalling and glucose uptake. However, their role in glucose uptake remains elusive, particularly in skeletal muscle cells. Treatment of differentiated L6 myotubes with the small molecule tankyrase inhibitor XAV939 resulted in insulin resistance as determined by impaired insulin-stimulated glucose uptake. Proteomic analysis identified 109 proteins that were down-regulated and 109 proteins that were up-regulated in response to XAV939. Among the down-regulated proteins there were several glucose transporter GLUT4 storage vesicle (GSV) proteins including RAB10, VAMP8, SORT1 as well as GLUT4 itself. Knock down of tankyrase1 in L6 myotubes also led to a reduction in the level of GSV proteins and impaired insulin-mediated glucose uptake. Inhibition of the proteasome rescued protein levels of GSV proteins as well as insulin-stimulated glucose uptake in XAV939-treated L6 myotubes. These studies reveal an important role for tankyrase in maintaining the stability of key GLUT4 regulatory proteins that in turn plays a role in regulating cellular insulin sensitivity.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Cell Culture

DISEASE(S): Type 2 Diabetes Mellitus

SUBMITTER: Zhiduan Su

LAB HEAD: David James

PROVIDER: PXD007182 | Pride | 2018-04-17

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20160528_QEplus_Tim_Ctrl1.raw	Raw
	20160528_QEplus_Tim_Ctrl2.raw	Raw
	20160528_QEplus_Tim_Ctrl3.raw	Raw
	20160528_QEplus_Tim_XAV939_1uM_24h1.raw	Raw
	20160528_QEplus_Tim_XAV939_1uM_24h2.raw	Raw

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Publications

Tankyrase modulates insulin sensitivity in skeletal muscle cells by regulating the stability of GLUT4 vesicle proteins.

Su Zhiduan Z Deshpande Vinita V James David E DE Stöckli Jacqueline J

The Journal of biological chemistry 20180418 22

Tankyrase 1 and 2, members of the poly(ADP-ribose) polymerase family, have previously been shown to play a role in insulin-mediated glucose uptake in adipocytes. However, their precise mechanism of action, and their role in insulin action in other cell types, such as myocytes, remains elusive. Treatment of differentiated L6 myotubes with the small molecule tankyrase inhibitor XAV939 resulted in insulin resistance as determined by impaired insulin-stimulated glucose uptake. Proteomic analysis of ...[more]

PMID: 29669812

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