The RabGAP TBC1D1 plays a central role in exercise-regulated glucose metabolism in skeletal muscle.

Abstract:

:Insulin and exercise stimulate glucose uptake into skeletal muscle via different pathways. Both stimuli converge on the translocation of the glucose transporter GLUT4 from intracellular vesicles to the cell surface. Two Rab guanosine triphosphatases-activating proteins (GAPs) have been implicated in this process: AS160 for insulin stimulation and its homolog, TBC1D1, are suggested to regulate exercise-mediated glucose uptake into muscle. TBC1D1 has also been implicated in obesity in humans and mice. We investigated the role of TBC1D1 in glucose metabolism by generating TBC1D1(-/-) mice and analyzing body weight, insulin action, and exercise. TBC1D1(-/-) mice showed normal glucose and insulin tolerance, with no difference in body weight compared with wild-type littermates. GLUT4 protein levels were reduced by ∼40% in white TBC1D1(-/-) muscle, and TBC1D1(-/-) mice showed impaired exercise endurance together with impaired exercise-mediated 2-deoxyglucose uptake into white but not red muscles. These findings indicate that the RabGAP TBC1D1 plays a key role in regulating GLUT4 protein levels and in exercise-mediated glucose uptake in nonoxidative muscle fibers.

journal_name

Diabetes

journal_title

Diabetes

authors

Stöckli J,Meoli CC,Hoffman NJ,Fazakerley DJ,Pant H,Cleasby ME,Ma X,Kleinert M,Brandon AE,Lopez JA,Cooney GJ,James DE

doi

10.2337/db13-1489

subject

Has Abstract

pub_date

2015-06-01 00:00:00

pages

1914-22

issue

6

eissn

0012-1797

issn

1939-327X

pii

db13-1489

journal_volume

64

pub_type

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