Quantitative PCR tissue expression profiling of the human SGLT2 gene and related family members

Chen, Jian; Williams, Sylvain; Ho, Samantha; Loraine, Howard; Hagan, Deborah; Whaley, Jean M.; Feder, John N.

doi:10.1007/s13300-010-0006-4

Cited by 257 publications

(236 citation statements)

References 39 publications

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“…37 A possible role for SMIT in degenerative processes is currently under exploration. The constitutive SMIT levels in the brain 17 were found moderately increased in the hippocampus of aged mice; 38 however, severity of tissue damage was not related to SMIT expression in TgCRND8, a mouse model of Alzheimer's disease-like amyloid pathology. 39 …”

Section: Osmolyte Pathway Activation In Dmmentioning

confidence: 90%

Activation of osmolyte pathways in inflammatory myopathy and Duchenne muscular dystrophy points to osmoregulation as a contributing pathogenic mechanism

Paepe

Martin

Herbelet

et al. 2016

Laboratory Investigation

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Alongside well-known nuclear factor κB (NFκB) and its associated cytokine networks, nuclear factor of activated T cells 5 (NFAT5), the master regulator of cellular osmoprotective programs, comes forward as an inflammatory regulator. To gain insight into its yet unexplored role in muscle disease, we studied the expression of NFAT5 target proteins involved in osmolyte accumulation: aldose reductase (AR), taurine transporter (TauT), and sodium myo-inositol co-transporter (SMIT). We analyzed idiopathic inflammatory myopathy and Duchenne muscular dystrophy muscle biopsies and myotubes in culture, using immunohistochemistry, immunofluorescence, and western blotting. We report that the level of constitutive AR was upregulated in patients, most strongly so in Duchenne muscular dystrophy. TauT and SMIT expression levels were induced in patients' muscle fibers, mostly representing regenerating and atrophic fibers. In dermatomyositis, strong staining for AR, TauT, and SMIT in atrophic perifascicular fibers was accompanied by staining for other molecular NFAT5 targets, including chaperones, chemokines, and inducible nitric oxide synthase. In these fibers, NFAT5 and NFκB p65 staining coincided, linking both transcription factors with this important pathogenic hallmark. In sporadic inclusion body myositis, SMIT localized to inclusions inside muscle fibers. In addition, SMIT was expressed by a substantial subset of muscle-infiltrating macrophages and T cells in patient biopsies. Our results indicate that osmolyte pathways may contribute to normal muscle functioning, and that activation of AR, TauT, and SMIT in muscle inflammation possibly contributes to the tissue's failing program of damage control.

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Section: Osmolyte Pathway Activation In Dmmentioning

confidence: 90%

Activation of osmolyte pathways in inflammatory myopathy and Duchenne muscular dystrophy points to osmoregulation as a contributing pathogenic mechanism

Paepe

Martin

Herbelet

et al. 2016

Laboratory Investigation

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“…PCR data show SGLT2 expression to be highly specific to the kidney and that the signal for renal expression was 100-fold higher in the kidney than in the next highest tissue observed (the ileum) (5). SGLT2 is expressed predominantly in the luminal brush border of the renal cortex (6).…”

Section: Sodium Glucose Cotransporter 2 (Sglt2)mentioning

confidence: 96%

Dapagliflozin Is Effective as Add-on Therapy to Sitagliptin With or Without Metformin: A 24-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study

et al. 2014

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OBJECTIVETo assess the efficacy and safety of dapagliflozin as add-on therapy in patients with type 2 diabetes who were inadequately controlled with a dipeptidyl peptidase-4 inhibitor with or without metformin. RESEARCH DESIGN AND METHODSIn this 24-week, multicenter, randomized, double-blind, placebo-controlled, parallelgroup, phase 3 study with a 24-week blinded extension period, 432 patients were randomized to receive dapagliflozin 10 mg/day or placebo added to sitagliptin (100 mg/ day) 6 metformin ( ‡1,500 mg/day). RESULTSBaseline HbA 1c and FPG levels were 7.9% (63.0 mmol/mol) and 162.2 mg/dL (9.0 mmol/L) for the dapagliflozin group and 8.0% (64.0 mmol/mol) and 163 mg/dL (9.0 mmol/L) for placebo. At week 24, dapagliflozin significantly reduced mean HbA 1c levels (-0.5% [-4.9 . Similar results were observed when data were stratified by background therapy. Glycemic and weight benefits observed at week 24 were maintained through week 48. Changes from baseline in systolic blood pressure at week 8 were not significantly different between treatment groups. Over 48 weeks, fewer patients receiving dapagliflozin were discontinued or rescued for failing to achieve glycemic targets compared with placebo. Adverse events were balanced between groups, and discontinuation rates were low. At week 48, signs and symptoms suggestive of genital infection were more frequent with dapagliflozin (9.8%) than with placebo (0.4%). Signs and symptoms suggestive of urinary tract infection were balanced between dapagliflozin (6.7%) and placebo (6.2%). CONCLUSIONSThese results suggest that in patients with type 2 diabetes, inadequately controlled on sitagliptin with or without metformin, add-on treatment with dapagliflozin provides additional clinical benefit and is well tolerated.

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“…In bovine, low concentrations of Sglt2 mRNA were also observed in small intestine, liver, lung, spleen, mammary gland, skeletal muscle, and ciliary epithelium (12,56,57). In humans, by real-time PCR the highest concentration of Sglt2 mRNA was observed in kidneys, but a limited expression was also detected in various extrarenal organs/tissues including small intestine, liver, brain, prostate, and testis (59), whereas recent studies indicated a highly kidney-specific expression of Sglt2 mRNA (13). Western blots and immunocytochemical studies using commercial polyclonal antibodies against SGLT2 have been reported.…”

mentioning

confidence: 95%

Expression of Na⁺-d-glucose cotransporter SGLT2 in rodents is kidney-specific and exhibits sex and species differences

Sabolić

Vrhovac

Eror

et al. 2012

American Journal of Physiology-Cell Physiology

166

147

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With a novel antibody against the rat Na ϩ -D-glucose cotransporter SGLT2 (rSGLT2-Ab), which does not cross-react with rSGLT1 or rSGLT3, the ϳ75-kDa rSGLT2 protein was localized to the brush-border membrane (BBM) of the renal proximal tubule S1 and S2 segments (S1 Ͼ S2) with femaledominant expression in adult rats, whereas rSglt2 mRNA expression was similar in both sexes. Castration of adult males increased the abundance of rSGLT2 protein; this increase was further enhanced by estradiol and prevented by testosterone treatment. In the renal BBM vesicles, the rSGLT1-independent uptake of [14 C]-␣-methyl-D-glucopyranoside was similar in females and males, suggesting functional contribution of another Na ϩ -D-glucose cotransporter to glucose reabsorption. Since immunoreactivity of rSGLT2-Ab could not be detected with certainty in rat extrarenal organs, the SGLT2 protein was immunocharacterized with the same antibody in wild-type (WT) mice, with SGLT2-deficient (Sglt2 knockout) mice as negative control. In WT mice, renal localization of mSGLT2 protein was similar to that in rats, whereas in extrarenal organs neither mSGLT2 protein nor mSglt2 mRNA expression was detected. At variance to the findings in rats, the abundance of mSGLT2 protein in the mouse kidneys was male dominant, whereas the expression of mSglt2 mRNA was female dominant. Our results indicate that in rodents the expression of SGLT2 is kidney-specific and point to distinct sex and species differences in SGLT2 protein expression that cannot be explained by differences in mRNA.

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Quantitative PCR tissue expression profiling of the human SGLT2 gene and related family members

Cited by 257 publications

References 39 publications

Activation of osmolyte pathways in inflammatory myopathy and Duchenne muscular dystrophy points to osmoregulation as a contributing pathogenic mechanism

Activation of osmolyte pathways in inflammatory myopathy and Duchenne muscular dystrophy points to osmoregulation as a contributing pathogenic mechanism

Dapagliflozin Is Effective as Add-on Therapy to Sitagliptin With or Without Metformin: A 24-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study

Expression of Na⁺-d-glucose cotransporter SGLT2 in rodents is kidney-specific and exhibits sex and species differences

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Quantitative PCR tissue expression profiling of the human SGLT2 gene and related family members

Cited by 257 publications

References 39 publications

Activation of osmolyte pathways in inflammatory myopathy and Duchenne muscular dystrophy points to osmoregulation as a contributing pathogenic mechanism

Activation of osmolyte pathways in inflammatory myopathy and Duchenne muscular dystrophy points to osmoregulation as a contributing pathogenic mechanism

Dapagliflozin Is Effective as Add-on Therapy to Sitagliptin With or Without Metformin: A 24-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study

Expression of Na+-d-glucose cotransporter SGLT2 in rodents is kidney-specific and exhibits sex and species differences

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Expression of Na⁺-d-glucose cotransporter SGLT2 in rodents is kidney-specific and exhibits sex and species differences