TY - JOUR
T1 - Human sodium/inositol cotransporter 2 (SMIT2) transports inositols but not glucose in L6 cells
AU - Lin, Xiaobo
AU - Ma, Lina
AU - Fitzgerald, Robin L.
AU - Ostlund, Richard E.
N1 - Funding Information:
The work was supported by NIH Grants R01 DK58698 , P30 DK56341 and P60 DK20579 .
PY - 2009/1/15
Y1 - 2009/1/15
N2 - To characterize the function of the sodium/inositol symporter SMIT2 in skeletal muscle, human SMIT2 cDNA was transfected into L6 myoblasts using pcDNA3.1 expression vector. Compared with the pcDNA3.1 vector only transfection, this overexpression increased the uptake of [3H]d-chiro-inositol (DCI) by 159-fold. [3H]myo-Inositol uptake increased by 37-fold. In contrast, [14C]d-glucose, [14C]2-deoxy-d-glucose, or [14C]3-O-methyl-d-glucose uptake remained unchanged in the presence of either 0, 5.5, or 25 mM unlabeled glucose. The Km of DCI and myo-inositol for DCI uptake was 111.0 and 158.0 μM, respectively, whereas glucose competed for DCI uptake with a Ki of 6.1 mM. Insulin treatment of non-transfected L6 cells (2 μM for 24 h) increased [3H]DCI specific uptake 18-fold. DCI transport is up regulated by insulin and competitively inhibited by millimolar levels of glucose. Therefore, expression and/or function of SMIT2, a high affinity transporter specific for DCI and myo-inositol, may be reduced in diabetes mellitus, insulin resistance and polycystic ovary syndrome causing the abnormal DCI metabolism observed in these conditions.
AB - To characterize the function of the sodium/inositol symporter SMIT2 in skeletal muscle, human SMIT2 cDNA was transfected into L6 myoblasts using pcDNA3.1 expression vector. Compared with the pcDNA3.1 vector only transfection, this overexpression increased the uptake of [3H]d-chiro-inositol (DCI) by 159-fold. [3H]myo-Inositol uptake increased by 37-fold. In contrast, [14C]d-glucose, [14C]2-deoxy-d-glucose, or [14C]3-O-methyl-d-glucose uptake remained unchanged in the presence of either 0, 5.5, or 25 mM unlabeled glucose. The Km of DCI and myo-inositol for DCI uptake was 111.0 and 158.0 μM, respectively, whereas glucose competed for DCI uptake with a Ki of 6.1 mM. Insulin treatment of non-transfected L6 cells (2 μM for 24 h) increased [3H]DCI specific uptake 18-fold. DCI transport is up regulated by insulin and competitively inhibited by millimolar levels of glucose. Therefore, expression and/or function of SMIT2, a high affinity transporter specific for DCI and myo-inositol, may be reduced in diabetes mellitus, insulin resistance and polycystic ovary syndrome causing the abnormal DCI metabolism observed in these conditions.
KW - DCI
KW - Diabetes
KW - Glucose
KW - Insulin resistance
KW - PCOS
KW - Pinitol
KW - SMIT2
KW - d-chiro-Inositol
KW - myo-Inositol
UR - http://www.scopus.com/inward/record.url?scp=58049097210&partnerID=8YFLogxK
U2 - 10.1016/j.abb.2008.11.008
DO - 10.1016/j.abb.2008.11.008
M3 - Article
C2 - 19032932
AN - SCOPUS:58049097210
SN - 0003-9861
VL - 481
SP - 197
EP - 201
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 2
ER -