ライフサイエンスコーパス: SGLT2

1 by two Na+/glucose cotransporters (SGLT1 and SGLT2).

2 al sodium-dependent glucose cotransporter 2 (SGLT2).

3 re potent and highly selective inhibitors of SGLT2.

4 Significant stimulation of SGLT2 activity also occurred in opossum kidney cells cot

5 e-associated protein (MAP17), that increased SGLT2 activity in RNA-injected Xenopus oocytes by two or

6 sodium/glucose cotransporter 2-encoding gene SGLT2 (also known as SLC5A2) in the family that segregat

7 n consisting of amino acids 1-380 of porcine SGLT2 and amino acids 381-662 of porcine SGLT1.

8 d in opossum kidney cells cotransfected with SGLT2 and MAP17.

9 sorption of glucose in the kidney along with SGLT2 and SGLT1.

10 1 transports both glucose and galactose, but SGLT2 and SGLT3 transport only glucose) with amino acid

11 sidue 460 (threonine in SGLT1, and serine in SGLT2 and SGLT3) are involved in hydrogen bonding to O4

12 ing that this nephron segment also expresses SGLT2 and that the kidneys and intestine show significan

13 e injected i.v. into wild-type, Sglt1(-/-) , Sglt2(-/-) and Glut2(-/-) mice and their dynamic whole-b

14 alpha and of the glucose transporters SGLT1, SGLT2, and GLUT1.

15 Reabsorption is primarily handled by SGLT2, and SGLT2-specific inhibitors, including dapaglif

16 hrough the Na(+)-coupled glucose transporter SGLT2, and specific inhibitors of SGLT2 are now availabl

17 gar binding; (iii) K0.5 for Na+ was lower in SGLT2; and (iv) the Hill coefficient for Na+ was 1 for S

18 t many of the kinetic properties observed in SGLT2 are expected by simply reducing the Na+/glucose co

19 ransporter SGLT2, and specific inhibitors of SGLT2 are now available to patients with diabetes to inc

20 nhibitors of sodium-glucose cotransporter 2 (SGLT2) are a novel class of antidiabetes drugs, and memb

21 he sodium-dependent glucose cotransporter 2 (SGLT2) as a method of maintaining glucose homeostasis in

22 (iv) the Hill coefficient for Na+ was 1 for SGLT2 but 2 for SGLT1.

23 xperiments showed that NHE3 colocalizes with SGLT2 but not SGLT1 in the rat renal proximal tubule.

24 -dependent, low affinity glucose transporter SGLT2 cloned from pig kidney is 76% identical (at the am

25 ent without any identifiable mutation in the SGLT2 coding gene (SLC5A2) displayed homozygosity for a

26 SGLT2 deficiency did not associate with volume depletion

27 mouse kidney and generated and characterized SGLT2-deficient mice.

28 the behavioral and metabolic consequences of SGLT2 deletion are unknown.

29 On the db/db background, SGLT2 deletion prevented fasting hyperglycemia, and plas

30 Prevention of renal glucose reabsorption by SGLT2 deletion reduced HFD- and obesity-associated hyper

31 SGLT2 deletion resulted in a threefold increase in urine

32 (i) immunohistochemical mapping of SGLT1 and SGLT2 distribution in tumors; (ii) measurement of glucos

33 an order of magnitude higher for SGLT2; (ii) SGLT2 excluded galactose, suggesting discrete sugar bind

34 SGLT2 exhibited Na+-dependent presteady-state currents w

35 presteady-state and steady-state kinetics of SGLT2 expressed in Xenopus oocytes.

36 Instead, in the kidneys, SGLT2 functionally interacts with the sodium-hydrogen ex

37 rter protein sodium-glucose cotransporter 2 (SGLT2) has emerged as a promising way to control blood g

38 In conclusion, SGLT2-I treatment improves impaired glucose effectivenes

39 l hyperglycemic-hyperinsulinemic clamp after SGLT2-I treatment, E-Rd increased by normalizing glucose

40 a sodium-glucose cotransporter 2 inhibitor (SGLT2-I) for 7 days.

41 The most potent inhibitors of SGLT2 (IC50 = 9-23 nM) were considerably weaker inhibito

42 y 3 mM) was an order of magnitude higher for SGLT2; (ii) SGLT2 excluded galactose, suggesting discret

43 a is freely filtered by the kidney, binds to SGLT2 in the apical membranes of the early proximal tubu

44 The sodium glucose cotransporter SGLT2 in the early proximal tubule is the major pathway

45 h familial renal glucosuria, but the role of SGLT2 in the kidney is incompletely understood.

46 Here, we determined the localization of SGLT2 in the mouse kidney and generated and characterize

47 or of the renal sodium-glucose cotransporter SGLT2 in vitro and characterized its in vitro and in viv

48 ery of the novel O-xyloside 7c that inhibits SGLT2 in vitro and urinary glucose reabsorption in vivo.

49 Inhibition of SGLT2 increases urinary glucose and calorie excretion, t

50 SGLT2 inhibition also is associated with an acute, dose-

51 SGLT2 inhibition also prevented inflammation via inhibit

52 Taken together, these data support SGLT2 inhibition as a viable insulin-independent treatme

53 We found that SGLT2 inhibition caused marked decreases in systolic blo

54 s are now investigating the potential use of SGLT2 inhibition in patients who have HF with and withou

55 wering, we also explore the potential use of SGLT2 inhibition in patients without T2D with HF or at r

56 otential mechanisms of beneficial effects of SGLT2 inhibition in the progression of diabetic renal di

57 SGLT2 inhibition is also associated with preservation of

58 However, glucosuria induction following SGLT2 inhibition is associated with a paradoxical increa

59 Although SGLT2 inhibition may have potential application beyond T

60 In summary, our study showed that SGLT2 inhibition modulates renal lipid metabolism and in

61 Effective SGLT2 inhibition needs adequate glomerular filtration an

62 Furthermore, the effect of SGLT2 inhibition on renal lipid content and inflammation

63 provide a unique insight into the effects of SGLT2 inhibition on whole body metabolism.

64 SGLT2 inhibition prevented renal lipid accumulation via

65 SGLT2 inhibition promotes natriuresis and osmotic diures

66 n in patients with type 2 diabetes following SGLT2 inhibition, despite an overall decrease in fasting

67 Sodium glucose cotransporter 2 (SGLT2) inhibition is a novel and promising treatment for

68 Matched SGLT2 inhibitor (n=22 830) and other glucose-lowering dr

69 the GLP-1 receptor agonist exenatide and the SGLT2 inhibitor dapagliflozin with exenatide or dapaglif

70 blood pressure and glycaemic effects of the SGLT2 inhibitor dapagliflozin with placebo in patients w

71 These data indicate that SGLT2 inhibitor elicits direct tubular effects in non-di

72 The mechanisms by which the SGLT2 inhibitor empagliflozin increases LDL cholesterol

73 94% of the total SGLT2 inhibitor exposure time was for use of dapaglifloz

74 iven by findings for empagliflozin (the only SGLT2 inhibitor for which data from a dedicated long-ter

75 We treated db/db mice with a selective SGLT2 inhibitor JNJ 39933673.

76 Our aim was to study the effects of SGLT2 inhibitor on circulating ZAG and ADI in nT2DM.

77 tes and a broad cardiovascular risk profile, SGLT2 inhibitor use was associated with reduced cardiova

78 Each SGLT2 inhibitor user was matched with three users of oth

79 el glucose lowering agent, empagliflozin, an SGLT2 inhibitor which targets the kidney to block glucos

80 thod is demonstrated by the synthesis of the SGLT2 inhibitor, canagliflozin (1a), from commercially a

81 hod was demonstrated by the synthesis of the SGLT2 inhibitor, canagliflozin.

82 the efficacy and safety of canagliflozin, an SGLT2 inhibitor, with glimepiride in patients with type

83 e discovery of a highly selective and potent SGLT2 inhibitor.

84 ucose with a sodium-glucose cotransporter 2 (SGLT2) inhibitor could improve insulin-mediated tissue g

85 hypoglycemic sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin and the insulin sensitize

86 nt with the sodium-glucose co-transporter-2 (SGLT2) inhibitor empagliflozin reduced albuminuria in pa

87 iflozin, the sodium-glucose cotransporter 2 (SGLT2) inhibitor, on renal hemodynamics and tubular func

88 gliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor.

89 nital tract infections were more common with SGLT2 inhibitors (odds ratios, 1.42 [CI, 1.06 to 1.90] a

90 These data suggest net protection of SGLT2 inhibitors against cardiovascular outcomes and dea

91 ecause of their unique glycosuric mechanism, SGLT2 inhibitors also reduce weight.

92 way, sodium-related physiological effects of SGLT2 inhibitors and clinical correlates of natriuresis,

93 Patients were divided into new users of SGLT2 inhibitors and new users of other glucose-lowering

94 onsistent with data from clinical studies on SGLT2 inhibitors and provide a rationale for the mode of

95 summarize the key pharmacodynamic effects of SGLT2 inhibitors and the clinical evidence that support

96 ntify significant differences between use of SGLT2 inhibitors and use of other glucose-lowering drugs

97 clinical trials, large clinical trials with SGLT2 inhibitors are now investigating the potential use

98 he way towards the development of carbasugar SGLT2 inhibitors as potential antidiabetic/antitumor age

99 e adenocarcinomas, and provide evidence that SGLT2 inhibitors block glucose uptake and reduce tumor g

100 synthetic route towards some small-molecule SGLT2 inhibitors by a chemo- and diastereospecific palla

101 However, maximal doses of SGLT2 inhibitors fail to inhibit >50% of the filtered gl

102 However, the clinical usage of carbasugar SGLT2 inhibitors has been underexplored, due to the leng

103 The first SGLT2 inhibitors have been approved as a new class of an

104 However, SGLT2 inhibitors in clinical development inhibit only 30

105 rmacokinetic and pharmacodynamic profiles of SGLT2 inhibitors in clinical trials and examine possible

106 The benefits of SGLT2 inhibitors in heart failure may be mediated by the

107 ce that support the rationale for the use of SGLT2 inhibitors in patients with HF who have T2D.

108 rong rationale to expect benefit from use of SGLT2 inhibitors in patients with type 2 diabetes at hig

109 produced, it is important to understand why SGLT2 inhibitors inhibit <50% of the filtered glucose lo

110 ure and diabetic glomerular hyperfiltration, SGLT2 inhibitors may induce protective effects on the ki

111 We aimed to establish the effects of SGLT2 inhibitors on cardiovascular events, death, and sa

112 Observations: The beneficial effect of SGLT2 inhibitors on heart failure cannot be explained by

113 ut not Sglt2-knockout mice, and injection of SGLT2 inhibitors prevented this binding.

114 SGLT2 inhibitors protected against the risk of major adv

115 Compared with other agents, SGLT2 inhibitors reduced body weight (mean difference, -

116 ponsible for the cardioprotective effects of SGLT2 inhibitors remain incompletely understood.

117 fraction may be mitigated by the actions of SGLT2 inhibitors to reduce blood pressure, body weight,

118 ecursors was synthesized and tested as SGLT1/SGLT2 inhibitors using a cell-based fluorescence assay o

119 ular mortality and morbidity in new users of SGLT2 inhibitors versus new users of other glucose-lower

120 ed with other glucose-lowering drugs, use of SGLT2 inhibitors was associated with a decreased risk of

121 ed with other glucose-lowering drugs, use of SGLT2 inhibitors was associated with decreased risk of c

122 nical practice guidelines now recommend that SGLT2 inhibitors with proven cardiovascular benefit be p

123 ealed the unexpected SAR of these carbasugar SGLT2 inhibitors, and enabled the discovery of a highly

124 ge pancreatic and prostate cancers, and that SGLT2 inhibitors, currently in use for treating diabetes

125 ynthetic route towards some novel carbasugar SGLT2 inhibitors, featuring an underexploited, regiosele

126 discovery of two highly selective and potent SGLT2 inhibitors, thereby paving the way towards the dev

127 ts), which provided data for seven different SGLT2 inhibitors.

128 f ongoing cardiovascular outcome trials with SGLT2 inhibitors.

129 accounts for the high kidney specificity of SGLT2 inhibitors.

130 of the potential cardiovascular benefits of SGLT2 inhibitors.

131 of canagliflozin therapy compared with other SGLT2 inhibitors.

132 Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs.

133 g effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors are already established, guidance is n

134 Carbasugar sodium-glucose cotransporter 2 (SGLT2) inhibitors are highly promising drug candidates f

135 2 diabetes, sodium-glucose cotransporter-2 (SGLT2) inhibitors are known to reduce glucose concentrat

136 rofile, the sodium-glucose co-transporter-2 (SGLT2) inhibitors empagliflozin and canagliflozin have b

137 Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve glycaemia in patients with typ

138 gon release, sodium-glucose cotransporter 2 (SGLT2) inhibitors induce stimulation of endogenous gluco

139 Sodium-glucose cotransporter 2 (SGLT2) inhibitors lower glycemia by enhancing urinary gl

140 gonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce glycaemia and weight, and impro

141 Sodium-glucose cotransporter-2 (SGLT2) inhibitors, including empagliflozin, dapagliflozi

142 ering agents-sodium-glucose cotransporter 2 (SGLT2) inhibitors-has been reported to decrease the risk

143 eported with sodium-glucose cotransporter 2 (SGLT2) inhibitors.

144 nfirm the physiologic relevance of the MAP17-SGLT2 interaction, we studied a cohort of 60 individuals

145 The low affinity SGLT2 is expressed in the S1 and S2 segments, has a Na+:

146 We found that SGLT2 is functionally expressed in pancreatic and prosta

147 It is widely accepted that SGLT2 is responsible for >80% of the reabsorption of the

148 SGLT2 is responsible for reabsorption of most of the glu

149 n of the Na(+)-glucose cotransporter type 2 (SGLT2) is currently being pursued as an insulin-independ

150 Strikingly, prevention of hyperglycemia by SGLT2 knockout in db/db mice preserved pancreatic beta-c

151 SGLT2 knockout mice were fed regular chow or a high-fat

152 SGLT2 knockout mice were protected from HFD-induced hype

153 Here, we used a SGLT2 knockout mouse to investigate the effect of increa

154 nd wild-type and Sglt1-knockout mice but not Sglt2-knockout mice, and injection of SGLT2 inhibitors p

155 stantial amounts of carbohydrate into urine, SGLT2-mediated glycosuria results in a progressive shift

156 It generally is accepted that SGLT2 mediates 90% of renal glucose reabsorption.

157 These results demonstrate that SGLT2 mediates glucose reabsorption in the early proxima

158 /-) mice compared with WT mice and varied in Sglt2(-/-) mice between 10 and 60%, inversely with the a

159 cose reabsorption was significantly lower in Sglt2(-/-) mice compared with WT mice and varied in Sglt

160 Sglt2(-/-) mice had glucosuria, polyuria, and increased

161 orption was 93 +/- 1% in WT and 21 +/- 6% in Sglt2(-/-) mice, respectively.

162 and plasma aldosterone levels were lower in Sglt2(-/-) mice.

163 in WT mice compared with no reabsorption in Sglt2(-/-) mice.

164 inary excretion of Me-4FDG in Sglt1(-/-) and Sglt2(-/-) mice.

165 into the heart of wild-type, Sglt1(-/-) and Sglt2(-/-) mice.

166 SGLT1 and SGLT2 mRNA and protein expression decreased under the th

167 We have found that the expression of SGLT2 mRNA and protein is increased in renal biopsies fr

168 The first aim of this study was to determine SGLT2 mRNA and protein levels in human and animal models

169 dient-dependent glucose transporter protein (SGLT2) mRNA and protein expression data reported in the

170 he index family, with simultaneous MCT12 and SGLT2 mutation.

171 Selective inhibition of SGLT2 over SGLT1 is critical for minimizing adverse side

172 on with MAP17 did not change the quantity of SGLT2 protein at the cell surface in either cell type.

173 t to db-db mice that had no changes in renal SGLT2 protein expression.

174 proach to map the distribution of functional SGLT2 proteins in rodents using positron emission tomogr

175 um-glucose cotransporters (SGLTs), SGLT1 and SGLT2, provide new therapeutic targets to reduce hypergl

176 ition of the sodium-glucose cotransporter 2 (SGLT2) reduces plasma glucose by limiting glucose absorp

177 ncoding for the Na(+)-glucose co-transporter SGLT2 (SLC5A2) associate with familial renal glucosuria,

178 bsorption is primarily handled by SGLT2, and SGLT2-specific inhibitors, including dapagliflozin, cana

179 itor of sodium-glucose cotransporter type 2 (SGLT2) that is marketed in United States, Europe, and ma

180 ted cellular glucose uptake independently of SGLT2, this did not account for AMPK activation.

181 pe (WT) mice, immunohistochemistry localized SGLT2 to the brush border membrane of the early proximal

182 en overexpressed in HEK293 cells, the mutant SGLT2 transporter did not efficiently translocate to the

183 The high density of functional SGLT2 transporters detected in the apical membrane of th

184 In contrast, SGLT2 transports poorly D-galactose and excludes 3-O-met

185 d controlled trials assessing the effects of SGLT2 treatment compared with controls.

186 ession of the glucose transporters SGLT1 and SGLT2 under hypoxic conditions which implies a possible

187 zin potently and selectively inhibited human SGLT2 versus human SGLT1, the major cotransporter of glu

188 The differences between SGLT1 and SGLT2 were that (i) the apparent affinity constant (K0.5

189 asis for a more thorough characterization of SGLT2 which would include the possible effects of its in