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Publication
Disruption of Adipose Rab10-Dependent Insulin Signaling Causes Hepatic Insulin
Resistance.
Authors Vazirani RP, Verma A, Sadacca LA, Buckman MS, Picatoste B, Beg M, Torsitano C,
Bruno JH, Patel RT, Simonyte K, Camporez JP, Moreira G, Falcone DJ, Accili D,
Elemento O, Shulman GI, Kahn BB, McGraw TE
Submitted By Submitted Externally on 9/20/2017
Status Published
Journal Diabetes
Year 2016
Date Published
Volume : Pages 65 : 1577 - 89
PubMed Reference 27207531
Abstract 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-specific Rab10 knockout (KO) mice. These
data demonstrate that the full effect of insulin on adipose glucose uptake is
the integrated effect of Rab10-dependent and Rab10-independent pathways,
establishing a divergence in insulin signal transduction to the regulation of
GLUT4 trafficking. In adipose-specific Rab10 KO female mice, the partial
inhibition of stimulated glucose uptake in adipocytes induces insulin resistance
independent of diet challenge. During euglycemic-hyperinsulinemic clamp, there
is no suppression of hepatic glucose production despite normal insulin
suppression of plasma free fatty acids. The impact of incomplete disruption of
stimulated adipocyte GLUT4 translocation on whole-body glucose homeostasis is
driven by a near complete failure of insulin to suppress hepatic glucose
production rather than a significant inhibition in muscle glucose uptake. These
data underscore the physiological significance of the precise control of
insulin-regulated trafficking in adipocytes.








Genes
SymbolDescription
Rab10RAB10, member RAS oncogene family

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