Absence of insulin receptor substrate-1 expression does not alter GLUT1 or GLUT4 abundance or contraction-stimulated glucose uptake by mouse skeletal muscle.
The purpose of this study was to determine the influence of insulin receptor substrate-1 (IRS-1) expression on GLUT1 and GLUT4 glucose transporter protein abundance, contraction-stimulated glucose uptake, and contraction-induced glycogen depletion by skeletal muscle. Mice (6 months old) from three genotypes were studied: wild-type (IRS-1(+/+)), heterozygous (IRS-1(+/-)) for the null allele, and IRS-1 knockouts (IRS-1(-/-)) lacking a functional IRS-1 gene. In situ muscle contraction was induced (electrical stimulation of sciatic nerve) in one hindlimb using contralateral muscles as controls. Soleus and extensor digitorum longus were dissected and 2-deoxyglucose uptake was measured in vitro. 2-Deoxyglucose uptake was higher in basal muscles (no contractions) from IRS-1(-/-) vs. both other genotypes. Contraction-stimulated 2-deoxyglucose uptake and glycogen depletion did not differ among genotypes. Muscle IRS-1 protein was undetectable for IRS-1(-/-) mice, and values were approximately 40 % lower in IRS-1(+/-) than in IRS-1(+/+) mice. No difference was found in IRS-1(+/+) compared to IRS-1(-/-) groups regarding muscle abundance of GLUT1 and GLUT4. Substantial reduction or elimination of IRS-1 did not alter the hallmark effects of contractions on muscle carbohydrate metabolism--activation of glucose uptake and glycogen depletion.
Dumke
C L
CL
Biodynamics Laboratory, Department of Kinesiology, University of Wisconsin, Madison, WI, USA.
Wetter
A C
AC
Arias
E B
EB
Kahn
C R
CR
Cartee
G D
GD
D000818:Animals; D001835:Body Weight; D003847:Deoxyglucose / Q000378:metabolism*; D004558:Electric Stimulation; D005260:Female; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D006003:Glycogen / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009004:Monosaccharide Transport Proteins / Q000032:analysis*; D009119:Muscle Contraction / Q000502:physiology*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000737:chemistry / Q000378:metabolism*; D009929:Organ Size; D010750:Phosphoproteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D012584:Sciatic Nerve
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D010750:Phosphoproteins; C495678:Slc2a1 protein, mouse; C495693:Slc2a4 protein, mouse; D006003:Glycogen; D003847:Deoxyglucose