The Experts below are selected from a list of 63 Experts worldwide ranked by ideXlab platform
Bruce R. Conway - One of the best experts on this subject based on the ideXlab platform.
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Effect of Canagliflozin on Renal Threshold for Glucose, Glycemia, and Body Weight in Normal and Diabetic Animal Models
PLoS ONE, 2012Co-Authors: Yin Liang, Kenji Arakawa, Kiichiro Ueta, Yasuaki Matsushita, Chiaki Kuriyama, Tonya L. Martin, Yi Liu, Bruce R. ConwayAbstract:Background Canagliflozin is a sodium glucose co-transporter (SGLT) 2 inhibitor in clinical development for the treatment of type 2 diabetes mellitus (T2DM). Methods 14C-Alpha-Methylglucoside uptake in Chinese hamster ovary-K cells expressing human, rat, or mouse SGLT2 or SGLT1; 3H-2-deoxy-d-glucose uptake in L6 myoblasts; and 2-electrode voltage clamp recording of oocytes expressing human SGLT3 were analyzed. Graded glucose infusions were performed to determine rate of urinary glucose excretion (UGE) at different blood glucose (BG) concentrations and the renal threshold for glucose excretion (RTG) in vehicle or canagliflozin-treated Zucker diabetic fatty (ZDF) rats. This study aimed to characterize the pharmacodynamic effects of canagliflozin in vitro and in preclinical models of T2DM and obesity. Results Treatment with canagliflozin 1 mg/kg lowered RTG from 415±12 mg/dl to 94±10 mg/dl in ZDF rats while maintaining a threshold relationship between BG and UGE with virtually no UGE observed when BG was below RTG. Canagliflozin dose-dependently decreased BG concentrations in db/db mice treated acutely. In ZDF rats treated for 4 weeks, canagliflozin decreased glycated hemoglobin (HbA1c) and improved measures of insulin secretion. In obese animal models, canagliflozin increased UGE and decreased BG, body weight gain, epididymal fat, liver weight, and the respiratory exchange ratio. Conclusions Canagliflozin lowered RTG and increased UGE, improved glycemic control and beta-cell function in rodent models of T2DM, and reduced body weight gain in rodent models of obesity.
Toshinao Goda - One of the best experts on this subject based on the ideXlab platform.
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sucrase isomaltase and hexose transporter gene expressions are coordinately enhanced by dietary fructose in rat jejunum
Journal of Nutrition, 1999Co-Authors: Kazuhiro Kishi, Takemi Tanaka, Makiko Igawa, Sachiko Takase, Toshinao GodaAbstract:We previously demonstrated that the levels of mRNAs of both sucrase-isomaltase (SI) and sodium/D-glucose transporter (SGLT1) are modulated by dietary sucrose in the rat jejunum. In the present study, we investigated whether the transcription of the gene coding SI is regulated by certain types of monosaccharides. Force-feeding a fructose and sucrose diet, (40% energy as fructose or sucrose) gave rise to parallel increases in the transcripts of SI and intestinal hexose transporters (SGLT1, GLUT5, and GLUT2) within 12 h. Force-feeding a glycerol-containing diet also caused an enhancement of SI, SGLT1, and GLUT2 mRNA levels. However, feeding the diet containing glucose or Alpha-Methylglucoside generally did not increase the transcript levels of SI or the intestinal hexose transporters. Nuclear run-on assays revealed that fructose as well as sucrose increased the transcription of both SI and GLUT5 genes and that the transcription rates of these genes were unaffected by glucose. These results suggest that fructose (or a metabolite) is capable of increasing the mRNA levels of SI and hexose transporters in the small intestine and that transcriptional regulation might play a pivotal role in the carbohydrate-induced coordinate enhancement of SI and fructose transporter gene expression
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dietary carbohydrates enhance lactase phlorizin hydrolase gene expression at a transcription level in rat jejunum
Biochemical Journal, 1998Co-Authors: Takemi Tanaka, Kazuhiro Kishi, Makiko Igawa, Sachiko Takase, Toshinao GodaAbstract:We have previously shown that dietary sucrose stimulates the lactase/phlorizin hydrolase (LPH) mRNA accumulation along with a rise in lactase activity in rat jejunum [Goda, Yasutake, Suzuki, Takase and Koldovský (1995) Am. J. Physiol. 268, G1066-G1073]. To elucidate the mechanisms whereby dietary carbohydrates enhance the LPH mRNA expression, 7-week-old rats that had been fed a low-carbohydrate diet (5.5% of energy as starch) were given diets containing various monosaccharides or sucrose for 12h. Among carbohydrates examined, fructose, sucrose, galactose and glycerol elicited an increase in LPH mRNA accumulation along with a rise in lactase activity in the jejunum. By contrast, glucose and Alpha-Methylglucoside were unable to elicit a significant increase in LPH mRNA levels. To explore a transcriptional mechanism for the carbohydrate-induced increases in LPH mRNA levels, we employed two techniques currently available to estimate transcriptional rate, i.e. RNA protection assays of pre-mRNA using an intron probe, and nuclear run-on assays. Both assays revealed that fructose elicited an increase in transcription of the LPH gene, and that the transcription of LPH was influenced only slightly, if at all, by glucose intake. These results suggest that certain monosaccharides such as fructose or their metabolite(s) are capable of enhancing LPH mRNA levels in the small intestine, and that transcriptional control might play a major role in the carbohydrate-induced increase of LPH mRNA expression.
Ewa Lojkowska - One of the best experts on this subject based on the ideXlab platform.
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dickeya solani sp nov a pectinolytic plant pathogenic bacterium isolated from potato solanum tuberosum
International Journal of Systematic and Evolutionary Microbiology, 2014Co-Authors: Jan M Van Der Wolf, Els H. Nijhuis, Malgorzata J. Kowalewska, Gerry S. Saddler, Neil Parkinson, John G. Elphinstone, Leighton Pritchard, Ian K. Toth, Ewa LojkowskaAbstract:Pectinolytic bacteria have been recently isolated from diseased potato plants exhibiting blackleg and slow wilt symptoms found in a number of European countries and Israel. These Gram-reaction-negative, motile, rods were identified as belonging to the genus Dickeya, previously the Pectobacterium chrysanthemi complex (Erwinia chrysanthemi, on the basis of production of a PCR product with the pelADE primers, 16S rRNA gene sequence analysis, fatty acid methyl esterase analysis, the production of phosphatases and the ability to produce indole and acids from Alpha-Methylglucoside. Differential physiological assays used previously to differentiate between strains of E chrysanthemi, showed that these isolates belonged to biovar 3. Eight of the isolates, seven from potato and one from hyacinth, were analysed together with 21 reference strains representing all currently recognized taxa within the genus Dickeya. The novel isolates formed a distinct genetic clade in multilocus sequence analysis (MLSA) using concatenated sequences of the intergenic spacer (IGS), as well as dnaX, recA, dnaN, fusA, gapA, purA, rpIB, rpoS and gyrA. Characterization by whole-cell MALDI-TOF mass spectrometry, pulsed field gel electrophoresis after digestion of whole-genome DNA with rare-cutting restriction enzymes, average nucleotide identity analysis and DNA DNA hybridization studies, showed that although related to Dickeya dadantii, these isolates represent a novel species within the genus Dickeya, for which the name Dickeya solani sp. nov. (type strain IPO 2222(T)=LMG25993(T)=NCPP134479(T)) is proposed.
Yin Liang - One of the best experts on this subject based on the ideXlab platform.
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Effect of Canagliflozin on Renal Threshold for Glucose, Glycemia, and Body Weight in Normal and Diabetic Animal Models
2013Co-Authors: Yin Liang, Kenji Arakawa, Kiichiro Ueta, Yasuaki Matsushita, Chiaki Kuriyama, Yi Liu, Tonya Martin, Bruce ConwayAbstract:Background: Canagliflozin is a sodium glucose co-transporter (SGLT) 2 inhibitor in clinical development for the treatment of type 2 diabetes mellitus (T2DM). Methods: 14 C-Alpha-Methylglucoside uptake in Chinese hamster ovary-K cells expressing human, rat, or mouse SGLT2 or SGLT1; 3 H-2-deoxy-D-glucose uptake in L6 myoblasts; and 2-electrode voltage clamp recording of oocytes expressing human SGLT3 were analyzed. Graded glucose infusions were performed to determine rate of urinary glucose excretion (UGE) at different blood glucose (BG) concentrations and the renal threshold for glucose excretion (RTG) in vehicle or canagliflozin-treated Zucker diabetic fatty (ZDF) rats. This study aimed to characterize the pharmacodynamic effects of canagliflozin in vitro and in preclinical models of T2DM and obesity. Results: Treatment with canagliflozin 1 mg/kg lowered RT G from 415612 mg/dl to 94610 mg/dl in ZDF rats while maintaining a threshold relationship between BG and UGE with virtually no UGE observed when BG was below RTG. Canagliflozin dose-dependently decreased BG concentrations in db/db mice treated acutely. In ZDF rats treated for 4 weeks, canagliflozin decreased glycated hemoglobin (HbA1c) and improved measures of insulin secretion. In obese animal models, canagliflozin increased UGE and decreased BG, body weight gain, epididymal fat, liver weight, and the respiratory exchange ratio
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Effects of canagliflozin on SGLT1-, SGLT2-, and facilitative glucose transporter-mediated glucose transport, and on SGLT3-induced currents.
2013Co-Authors: Yin Liang, Kenji Arakawa, Kiichiro Ueta, Yasuaki Matsushita, Chiaki Kuriyama, Yi Liu, Tonya Martin, Bruce ConwayAbstract:CHOK cells over-expressed with human, rat, or mouse SGLT1 or SGLT2 and rat L6 myoblast cells were used. AMG or 2-DG uptake was determined and IC50 values were calculated as described in Methods section. Data of human SGLT1 and SGLT2 were presented the summary of 5 studies. Other data presented the mean value of 2 experiments. Oocytes expressed with human SGLT3 were used to determine canagliflozin effect on DNJ-induced current.2-DG, 2-deoxy-d-glucose; AMG, Alpha-Methylglucoside; CHOK, Chinese hamster ovary-K; IC50, concentration required to inhibit 50% of activity; SGLT, sodium glucose co-transporter; DNJ, imino sugars 1-deoxynojirimycin.
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Effect of Canagliflozin on Renal Threshold for Glucose, Glycemia, and Body Weight in Normal and Diabetic Animal Models
PLoS ONE, 2012Co-Authors: Yin Liang, Kenji Arakawa, Kiichiro Ueta, Yasuaki Matsushita, Chiaki Kuriyama, Tonya L. Martin, Yi Liu, Bruce R. ConwayAbstract:Background Canagliflozin is a sodium glucose co-transporter (SGLT) 2 inhibitor in clinical development for the treatment of type 2 diabetes mellitus (T2DM). Methods 14C-Alpha-Methylglucoside uptake in Chinese hamster ovary-K cells expressing human, rat, or mouse SGLT2 or SGLT1; 3H-2-deoxy-d-glucose uptake in L6 myoblasts; and 2-electrode voltage clamp recording of oocytes expressing human SGLT3 were analyzed. Graded glucose infusions were performed to determine rate of urinary glucose excretion (UGE) at different blood glucose (BG) concentrations and the renal threshold for glucose excretion (RTG) in vehicle or canagliflozin-treated Zucker diabetic fatty (ZDF) rats. This study aimed to characterize the pharmacodynamic effects of canagliflozin in vitro and in preclinical models of T2DM and obesity. Results Treatment with canagliflozin 1 mg/kg lowered RTG from 415±12 mg/dl to 94±10 mg/dl in ZDF rats while maintaining a threshold relationship between BG and UGE with virtually no UGE observed when BG was below RTG. Canagliflozin dose-dependently decreased BG concentrations in db/db mice treated acutely. In ZDF rats treated for 4 weeks, canagliflozin decreased glycated hemoglobin (HbA1c) and improved measures of insulin secretion. In obese animal models, canagliflozin increased UGE and decreased BG, body weight gain, epididymal fat, liver weight, and the respiratory exchange ratio. Conclusions Canagliflozin lowered RTG and increased UGE, improved glycemic control and beta-cell function in rodent models of T2DM, and reduced body weight gain in rodent models of obesity.
Leighton Pritchard - One of the best experts on this subject based on the ideXlab platform.
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dickeya solani sp nov a pectinolytic plant pathogenic bacterium isolated from potato solanum tuberosum
International Journal of Systematic and Evolutionary Microbiology, 2014Co-Authors: Jan M Van Der Wolf, Els H. Nijhuis, Malgorzata J. Kowalewska, Gerry S. Saddler, Neil Parkinson, John G. Elphinstone, Leighton Pritchard, Ian K. Toth, Ewa LojkowskaAbstract:Pectinolytic bacteria have been recently isolated from diseased potato plants exhibiting blackleg and slow wilt symptoms found in a number of European countries and Israel. These Gram-reaction-negative, motile, rods were identified as belonging to the genus Dickeya, previously the Pectobacterium chrysanthemi complex (Erwinia chrysanthemi, on the basis of production of a PCR product with the pelADE primers, 16S rRNA gene sequence analysis, fatty acid methyl esterase analysis, the production of phosphatases and the ability to produce indole and acids from Alpha-Methylglucoside. Differential physiological assays used previously to differentiate between strains of E chrysanthemi, showed that these isolates belonged to biovar 3. Eight of the isolates, seven from potato and one from hyacinth, were analysed together with 21 reference strains representing all currently recognized taxa within the genus Dickeya. The novel isolates formed a distinct genetic clade in multilocus sequence analysis (MLSA) using concatenated sequences of the intergenic spacer (IGS), as well as dnaX, recA, dnaN, fusA, gapA, purA, rpIB, rpoS and gyrA. Characterization by whole-cell MALDI-TOF mass spectrometry, pulsed field gel electrophoresis after digestion of whole-genome DNA with rare-cutting restriction enzymes, average nucleotide identity analysis and DNA DNA hybridization studies, showed that although related to Dickeya dadantii, these isolates represent a novel species within the genus Dickeya, for which the name Dickeya solani sp. nov. (type strain IPO 2222(T)=LMG25993(T)=NCPP134479(T)) is proposed.