Glucose transporter isoform-3-null heterozygous mutation causes sexually dimorphic adiposity with insulin resistance.
We examined male and female glucose transporter isoform-3 (GLUT3; placenta)-null heterozygous(+/-) mutation-carrying mice and compared them with age- and sex-matched wild-type(+/+) littermates. No difference in postnatal (1-2 days, 6-7 days, 12-13 days, 20-21 days), postsuckling (1-2 mo), and adult (3-6 mo) growth pattern was seen except for an increase in body weight of 9- to 11-mo-old male but not female GLUT3(+/-) mice. This change in male mutant mice was associated with increased total body fat mass, perirenal and epididymal white adipose tissue weight, and hepatic lipid infiltration. These minimally glucose-intolerant male mutant mice demonstrated no change in caloric intake but a decline in basal metabolic rate and insulin resistance. No perturbation in basal circulating glucose concentrations but an increase in insulin concentrations, triglycerides, and total cholesterol was observed in GLUT3(+/-) male mice. Tissue analysis in males and females demonstrated diminished GLUT3 protein in GLUT3(+/-) brain and skeletal muscle with no change in brain and adipose tissue GLUT1 protein concentrations. Furthermore, the male GLUT3(+/-) mice expressed decreased insulin-responsive GLUT4 in white adipose tissue and skeletal muscle sarcolemma. We conclude that the GLUT3(+/-) male mice develop adult-onset adiposity with insulin resistance.
Ganguly
Amit
A
Division of Neonatology and Developmental Biology, Neonatal Research Center, Department of Pediatrics, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095-1752, USA.
Devaskar
Sherin U
SU
D050154:Adiposity / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001481:Basal Metabolism / Q000235:genetics / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000235:genetics / Q000502:physiology; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D004435:Eating / Q000235:genetics / Q000502:physiology; D005260:Female; D051274:Glucose Transporter Type 3 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006651:Histocytochemistry; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D020738:Leptin / Q000097:blood; D008099:Liver / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains
D001786:Blood Glucose; D051274:Glucose Transporter Type 3; D007328:Insulin; D020738:Leptin; C495689:Slc2a3 protein, mouse