Tripeptides of RS1 (RSC1A1) inhibit a monosaccharide-dependent exocytotic pathway of Na+-D-glucose cotransporter SGLT1 with high affinity.

The human gene RSC1A1 codes for a 67-kDa protein named RS1 that mediates transcriptional and post-transcriptional regulation of Na(+)-D-glucose cotransporter SGLT1. The post-transcriptional regulation occurs at the trans-Golgi network (TGN). We identified two tripeptides in human RS1 (Gln-Cys-Pro (QCP) and Gln-Ser-Pro (QSP)) that induce posttranscriptional down-regulation of SGLT1 at the TGN leading to 40-50% reduction of SGLT1 in plasma membrane.

RS1 (RSC1A1) regulates the exocytotic pathway of Na+-D-glucose cotransporter SGLT1.

The product of gene RSC1A1, named RS1, participates in transcriptional and posttranscriptional regulation of the sodium-d-glucose cotransporter SGLT1. Using coexpression in oocytes of Xenopus laevis, posttranscriptional inhibition of human SGLT1 (hSGLT1) and some other transporters by human RS1 (hRS1) was demonstrated previously. In the present study, histidine-tagged hRS1 was expressed in oocytes or Sf9 cells and purified using nickel(II)-charged nitrilotriacetic acid-agarose.

Synthesis of 18F-fluoroalkyl-beta-D-glucosides and their evaluation as tracers for sodium-dependent glucose transporters.

Unlabelled: Three omega-(18)F-fluoro-n-alkyl-beta-D-glucosides (alkyl = ethyl (5a)), n-butyl (5b), and n-octyl (5c)) were synthesized and evaluated as potential substrates for the sodium/D-glucose cotransporter SGLT1.

Methods: The ligands were prepared by (18)F-fluoride displacement of the corresponding tetraacetyl-protected tosylate alkylglucoside precursors in CH(3)CN, followed by hydrolysis of the protective acetate esters with NaOMe/MeOH. Transport of the nonradioactive analogs 5a, 5b, and 5c by the human sodium-D-glucose cotransporter hSGLT1 was characterized in vitro in oocytes of Xenopus laevis that expressed hSGLT1.

Synthesis and biologic evaluation of (11)c-methyl-d-glucoside, a tracer of the sodium-dependent glucose transporters.

Unlabelled: This study aimed to synthesize and to evaluate the biologic characteristics of (11)C labeled methyl-D-glucoside, a nonmetabolizable tracer that is selectively transported by sodium-dependent glucose transporters (SGLTs).

Methods: (11)C-Methyl-D-glucoside was prepared by methylation of glucose with (11)C-methyl triflate and was obtained as a mixture of anomers that were separated with high-performance liquid chromatography. The biodistribution of both the D- and L-isomers was determined in mice, and the presence of metabolites in the blood was investigated.