title: Insulin and SGK1 reduce the function of Na+/monocarboxylate transporter 1 (SMCT1/SLC5A8).
abstract: SMCTs move several important fuel molecules that are involved in lipid, carbohydrate, and amino acid metabolism, but their regulation has been poorly studied. Insulin controls the translocation of several solutes that are involved in energetic cellular metabolism, including glucose. We studied the effect of insulin on the function of human SMCT1 expressed in Xenopus oocytes. The addition of insulin reduced α-keto-isocaproate (KIC)-dependent22Na+uptake by 29%. Consistent with this result, the coinjection of SMCT1 with SGK1 cRNA decreased the KIC-dependent22Na+uptake by 34%. The reduction of SMCT1 activity by SGK1 depends on its kinase activity, and it was observed that the coinjection of SMCT1 with S442D-SGK1 (a constitutively active mutant) decreased the KIC-dependent22Na+uptake by 50%. In contrast, an SMCT1 coinjection with K127M-SGK1 (an inactive mutant) had no effect on the KIC-dependent Na+uptake. The decreasing SMCT1 function by insulin or SGK1 was corroborated by measuring [1-14C]acetate uptake and the electric currents of SMCT1-injected oocytes. Previously, we found that SMCT2/Slc5a12-mRNA, but not SMCT1/Slc5a8-mRNA, is present in zebrafish pancreas (by in situ hybridization); however, SLC5a8 gene silencing was associated with the development of human pancreatic cancer. We confirmed that the mRNA and protein of both transporters were present in rat pancreas using RT-PCR with specific primers, Western blot analysis, and immunohistochemistry. Additionally, significant propionate-dependent22Na+uptake occurred in pancreatic islets and was reduced by insulin treatment. Our data indicate that human SMCT1 is regulated by insulin and SGK1 and that both SMCTs are present in the mammalian pancreas.
authors.affiliation: Department of Physiology of Nutrition, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, Mexico.
authors.forename: Adriana
authors.initials: A
authors.lastname: López-Barradas
authors.affiliation: Department of Nephrology & Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, Mexico.
authors.forename: Tania
authors.initials: T
authors.lastname: González-Cid
authors.affiliation: Department of Nephrology & Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, Mexico.|Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, UNAM, Tlalpan, Mexico City, Mexico.
authors.forename: Norma
authors.initials: N
authors.lastname: Vázquez
authors.affiliation: Department of Nephrology & Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, Mexico.
authors.forename: Marisol
authors.initials: M
authors.lastname: Gavi-Maza
authors.affiliation: Department of Nephrology & Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, Mexico.
authors.forename: Adriana
authors.initials: A
authors.lastname: Reyes-Camacho
authors.affiliation: Department of Physiology of Nutrition, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, Mexico.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Velázquez-Villegas
authors.affiliation: Department of Nephrology & Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, Mexico.
authors.forename: Victoria
authors.initials: V
authors.lastname: Ramírez
authors.affiliation: Renal Division, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Kambiz
authors.initials: K
authors.lastname: Zandi-Nejad
authors.affiliation: Renal Division, Brigham and Women's Hospital, Boston, Massachusetts.|Veterans Affairs Boston Healthcare System, Boston, Massachusetts; and.
authors.forename: David B
authors.initials: DB
authors.lastname: Mount
authors.affiliation: Department of Physiology of Nutrition, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, Mexico.
authors.forename: Nimbe
authors.initials: N
authors.lastname: Torres
authors.affiliation: Department of Physiology of Nutrition, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, Mexico.
authors.forename: Armando R
authors.initials: AR
authors.lastname: Tovar
authors.affiliation: Physiology & Biomedical Engineering, Nephrology & Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Romero
authors.affiliation: Department of Nephrology & Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, Mexico.|Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, UNAM, Tlalpan, Mexico City, Mexico.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Gamba
authors.affiliation: Department of Nephrology & Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, Mexico; consueloplata@hotmail.com.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Plata
mesh_terms: D000818:Animals; D018076:DNA, Complementary / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D008297:Male; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D014982:Xenopus laevis / Q000378:metabolism; D015027:Zebrafish / Q000378:metabolism; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D018076:DNA, Complementary; D017874:Immediate-Early Proteins; D007328:Insulin; D027501:Monocarboxylic Acid Transporters; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D012964:Sodium; D000099184:Serum-Glucocorticoid Regulated Kinases; C476760:SLC5A8 protein, human
keywords: Na+-monocarboxylate cotransporter with high affinity for MCs (SMCT1); Na+-monocarboxylate cotransporter with low affinity for MCs (SMCT2); monocarboxylates; serum- and glucocorticoid-inducible kinase-1 (SGK1); solute carrier family 5 member 8 (SLC5A8); solute carrier family 5, member 12 (SLC5A12); α-keto-isocaproate