Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Adipose Rab10 Knockout Causes Insulin Resistance through Impaired Glucose Uptake

ABSTRACT: Insulin action in adipocytes affects whole-body insulin sensitivity. Studies of adipose-specific Glut4 knockout mice have established that adipose Glut4 contributes to the control of systemic glucose homeostasis. Presumably, this reflects a role for Glut4-mediated glucose transport in the regulation of secreted adipokines. In cultured 3T3-L1 adipocytes, Rab10 GTPase is required for insulin-stimulated translocation of Glut4 (Sano et al., 2007). The physiological importance of adipose Rab10 and the significance of its role in the control of Glut4 vesicle trafficking in vivo are unknown. Here we report that adipocytes from adipose-specific Rab10 knockout mice have a ~50% reduction in glucose uptake and Glut4 translocation to the cell surface in response to insulin, demonstrating a role for Rab10 in Glut4 trafficking. Moreover, hyperinsulinemic-euglycemic clamp shows decreased whole-body glucose uptake as well as impaired suppression of hepatic glucose production in adipose Rab10 knockout mice. Thus, fully functional Glut4 vesicle trafficking in adipocytes is critical for maintaining insulin sensitivity. Comparative transcriptome analysis of perigonadal adipose tissue demonstrates significant transcriptional similarities between adipose Rab10 knockout mice and adipose Glut4 knockout mice, consistent with the notion that the phenotypic similarities between the two models are mediated by reduced insulin-stimulated glucose transport into adipocytes. Transcriptome sequencing of perigonadal white adipose tissue

ORGANISM(S): Mus musculus

SUBMITTER: Akanksha Verma

PROVIDER: E-GEOD-70123 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Disruption of Adipose Rab10-Dependent Insulin Signaling Causes Hepatic Insulin Resistance.

Vazirani Reema P RP Verma Akanksha A Sadacca L Amanda LA Buckman Melanie S MS Picatoste Belen B Beg Muheeb M Torsitano Christopher C Bruno Joanne H JH Patel Rajesh T RT Simonyte Kotryna K Camporez Joao P JP Moreira Gabriela G Falcone Domenick J DJ Accili Domenico D Elemento Olivier O Shulman Gerald I GI Kahn Barbara B BB McGraw Timothy E TE

Diabetes 20160325 6

Insulin controls glucose uptake into adipose and muscle cells by regulating the amount of GLUT4 in the plasma membrane. The effect of insulin is to promote the translocation of intracellular GLUT4 to the plasma membrane. The small Rab GTPase, Rab10, is required for insulin-stimulated GLUT4 translocation in cultured 3T3-L1 adipocytes. Here we demonstrate that both insulin-stimulated glucose uptake and GLUT4 translocation to the plasma membrane are reduced by about half in adipocytes from adipose- ...[more]

PMID: 27207531

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Dataset Information

Adipose Rab10 Knockout Causes Insulin Resistance through Impaired Glucose Uptake

Publications

Disruption of Adipose Rab10-Dependent Insulin Signaling Causes Hepatic Insulin Resistance.

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