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Naoko Matsushita, Nanae Ishida, Miho Ibi, Maki Saito, Atsushi Sanbe, Hisashi Shimojo, Satoshi Suzuki, Hermann Koepsell, Yasuchika Takeishi, Yoshihiro Morino, Eiichi Taira, Yohei Sawa, Masamichi Hirose
Increased gene expression levels of sodium-glucose cotransporter 1 (SGLT1) are associated with hypertrophic and ischemic cardiomyopathy. However, it remains unclear whether chronic pressure overload increases SGLT1 expression, which in turn induces hypertrophic cardiomyopathy. We hypothesized that pressure overload could increase SGLT1 gene expression, leading to the development of hypertrophic cardiomyopathy.To create pressure overload-induced cardiomyopathy, transverse aortic constriction (TAC) was performed in SGLT1-deficient (SGLT1-/- ) and wild-type (WT) mice...
August 11, 2018: International Heart Journal
Peng Liao, Meifang Liao, Ling Li, Bie Tan, Yulong Yin
This study was conducted to determine the effect of 200 ng mL-1 and 2000 ng mL-1 deoxynivalenol (DON) on apoptosis, barrier function, nutrient transporter gene expression, and free amino acid variation as well as on mitochondrial biogenesis and function-related gene expression in the intestinal porcine epithelial cell line J2 (IPEC-J2) for 6 h, 12 h, and 24 h. Exposure to 200 ng mL-1 DON inhibited the cell viability and promoted cell cycle progression from the G2/M phase to the S phase ( P < 0.05). The data showed that the IPEC-J2 cell content of free amino acids, such as valine, methionine, leucine, and phenylalanine, was increased ( P < 0...
November 1, 2017: Toxicology Research
H Zhang, H Li, J Kidrick, E A Wong
The uptake of glucose is mediated mainly by the sodium-glucose cotransporter, SGLT1. Previous studies using quantitative PCR showed that SGLT1 mRNA was induced in the yolk sac and in the small intestine prior to hatch. However, PCR analysis did not allow for the localization of cells expressing SGLT1 mRNA. The objective of this study was to use in situ hybridization to identify cells in the yolk sac and small intestine that expressed SGLT1 mRNA during the transition from late embryogenesis to early post-hatch...
August 1, 2018: Poultry Science
Sabrina Oerter, Carola Förster, Michael Bohnert
In many forensic cases, the existence of a traumatic brain injury (TBI) is an essential factor, and the determination of the survival time is nearly as important as the determination of whether or not a trauma exists. Since it is known that glucose uptake increases in injured brain cells in order to perpetuate the neuronal integrity, this study focuses on the pathomechanism of brain glucose supply via sodium/glucose cotransporters 1 and 2 (SGLT1, SGLT2) following traumatization. Human cerebrum tissue of male and female individuals who died following TBI was taken from the contusional and contralateral regions, as well as from individuals deceased due to cardiac arrest (control group)...
August 2, 2018: International Journal of Legal Medicine
Shin Fukudo, Yuka Endo, Michio Hongo, Atsushi Nakajima, Tatsuya Abe, Hiroyuki Kobayashi, Tomohiro Nakata, Toshio Nakajima, Kanako Sameshima, Kohei Kaku
BACKGROUND: Mizagliflozin is a novel oral sodium-glucose cotransporter 1 (SGLT1) inhibitor that increases luminal glucose and water. This study assessed the efficacy and safety of mizagliflozin in patients with functional constipation. METHODS: In this multicentre, randomised, double-blind phase 2 trial at 32 hospitals and community outpatient clinics in Japan, we enrolled patients with functional constipation or constipation-predominant irritable bowel syndrome, aged 20 years or older...
July 25, 2018: Lancet. Gastroenterology & Hepatology
Stefan D Anker, Javed Butler
No abstract text is available yet for this article.
July 19, 2018: ESC Heart Failure
Anne Sebastiani, Frederik Greve, Christina Gölz, Carola Y Förster, Hermann Koepsell, Serge C Thal
Acute cerebral lesions are associated with dysregulation of brain glucose homeostasis. Previous studies showed that knockdown of Na+ -D-glucose cotransporter SGLT1 impaired outcome after middle cerebral artery occlusion and that widely expressed intracellular RS1 (RSC1A1) is involved in transcriptional and posttranslational downregulation of SGLT1. In the present study, we investigated whether SGLT1 is upregulated during traumatic brain injury (TBI) and whether removal of RS1 in mice (RS1-KO) influences SGLT1 expression and outcome...
July 19, 2018: Journal of Neurochemistry
Grégory Jacquillet, Edward S Debnam, Robert J Unwin, Joanne Marks
Artificial sweeteners are extensively used by the food industry to replace sugar in food and beverages and are widely considered to be a healthy alternative. However, recent data suggest that artificial sweeteners may impact intestinal glucose absorption and that they might lead to glucose intolerance. Moreover, chronic consumption of artificial sweeteners has also been linked to detrimental changes in renal function. Using an in vivo approach, our study aimed to determine if short-term infusion of the artificial sweetener saccharin can alter renal function and renal glucose absorption...
July 2018: Physiological Reports
Christian Seerup Frandsen, Thomas Fremming Dejgaard, Sten Madsbad, Jens Juul Holst
Despite intensified insulin treatment, many persons with type 1 diabetes (T1D) do not achieve glycemic and metabolic targets. Consequently, non-insulin chemical therapies that improve glycemic control and metabolic parameters without increasing the risk of adverse events (including hypoglycemia) are of interest as adjunct therapies to insulin. Areas covered: In this review, the authors discuss the efficacy and safety of non-insulin therapies, including pramlintide, glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 inhibitors (DPP-4), sodium-glucose cotransporter (SGLT1 and SGLT2) inhibitors, metformin, sulfonylureas, and thiazolidinediones as add-on therapies to insulin in T1D...
June 2018: Expert Opinion on Pharmacotherapy
Kim A Connelly, Yanling Zhang, Jean-François Desjardins, Kerri Thai, Richard E Gilbert
BACKGROUND: Inhibiting both type 1 and 2 sodium-glucose linked cotransporter (SGLT1/2) offers the potential to not only increase glucosuria beyond that seen with selective SGLT2 inhibition alone but to reduce glucose absorption from the gut and to thereby also stimulate glucagon-like peptide 1 secretion. However, beyond the kidney and gut, SGLT1 is expressed in a range of other organs particularly the heart where it potentially assists GLUT-mediated glucose transport. Since cardiac myocytes become more reliant on glucose as a fuel source in the setting of stress, the present study sought to compare the effects of dual SGLT1/2 inhibition with selective SGLT2 inhibition in the normal and diseased heart...
July 7, 2018: Cardiovascular Diabetology
Masamichi Hirose, Naoko Matsushita, Nanae Ishida, Miho Ibi, Maki Saito
 It is well-known that metabolic remodeling occurs in the presence of cardiomyopathy induced by cardiac ischemia and hypertrophy, and diabetes mellitus. It is also known that a novel cardiac glucose transporter, sodium-glucose co-transporter 1 (SGLT1), is expressed in the human heart. However, the role of SGLT1 in the development of cardiac metabolic remodeling is still unclear. Recent studies demonstrated that SGLT1 activation improves ischemia-reperfusion-induced cardiac injury, and increased SGLT1 gene expression is observed in hypertrophic, ischemic, and diabetic cardiomyopathy in human hearts...
2018: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
Anita T Layton
Diabetes induces glomerular hyperfiltration, affects kidney function, and may lead to chronic kidney diseases. A novel therapeutic treatment for diabetic patients targets the sodium-glucose cotransporter isoform 2 (SGLT2) in the kidney. SGLT2 inhibitors enhance urinary glucose, [Formula: see text] and fluid excretion and lower hyperglycemia in diabetes by inhibiting [Formula: see text] and glucose reabsorption along the proximal convoluted tubule. A goal of this study is to predict the effects of SGLT2 inhibitors in diabetic patients with and without chronic kidney diseases...
June 28, 2018: Biological Cybernetics
Thomas Danne, Bertrand Cariou, Phillip Banks, Michael Brandle, Helmut Brath, Edward Franek, Jake A Kushner, Pablo Lapuerta, Darren K McGuire, Anne L Peters, Sangeeta Sawhney, Paul Strumph
OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of the dual SGLT1 and SGLT2 inhibitor sotagliflozin compared with placebo when combined with optimized insulin in adults with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: In a double-blind, 52-week, international phase 3 trial, adults with T1D were randomized to placebo ( n = 258) or once-daily oral sotagliflozin 200 mg ( n = 261) or 400 mg ( n = 263) after 6 weeks of insulin optimization...
June 24, 2018: Diabetes Care
John B Buse, Satish K Garg, Julio Rosenstock, Timothy S Bailey, Phillip Banks, Bruce W Bode, Thomas Danne, Jake A Kushner, Wendy S Lane, Pablo Lapuerta, Darren K McGuire, Anne L Peters, John Reed, Sangeeta Sawhney, Paul Strumph
OBJECTIVE: Evaluate the efficacy and safety of the dual sodium-glucose cotransporter 1 (SGLT1) and SGLT2 inhibitor sotagliflozin in combination with optimized insulin in type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: The inTandem1 trial, a double-blind, 52-week phase 3 trial, randomized North American adults with T1D to placebo ( n = 268), sotagliflozin 200 mg ( n = 263), or sotagliflozin 400 mg ( n = 262) after 6 weeks of insulin optimization. The primary end point was HbA1c change from baseline at 24 weeks...
June 24, 2018: Diabetes Care
J S Garcia, J A Byrd, E A Wong
Campylobacter is a bacterium that colonizes the lower gastrointestinal tract of poultry and may influence the intestinal environment to promote its survival. The objective of this study was to characterize the effects of Campylobacter challenge on the mRNA abundance of nutrient transporters and host defense peptides (HDP), such as the avian β-defensins (AvBD) and liver expressed antimicrobial peptide 2 (LEAP2). On the day of hatch, broiler chicks were challenged with one of three (106, 107, 108 colony-forming units, cfu) levels of Campylobacter jejuni...
June 20, 2018: Poultry Science
Zichao Wang, Huiru Zhang, Yingbin Shen, Xiaoxiao Zhao, Xueqin Wang, Jiaqi Wang, Kun Fan, Xiaobei Zhan
Fungal polysaccharides are mainly taken orally, so it is very important to study the absorption mechanism of which in vivo for understanding its biological activities. In this work, a polysaccharide fraction (GLP) was purified from G. lucidum by water extraction and alcohol precipitation. Physicochemical characterization indicated that GLP had a molecular weight of 108 kDa and consisted of glucose (35.56%), xylose (40.11%), rhamnose (16.45%) and l-arabinose (7.88%) in a molar radio of 4.51: 5.09: 2.88: 1...
June 18, 2018: International Journal of Biological Macromolecules
Thomas Danne, Torben Biester, Olga Kordonouri
The sodium-glucose cotransporter type 1 (SGLT1) is the primary transporter for absorption of glucose and galactose in the gastrointestinal tract. Inhibition blunts and delays postprandial glucose (PPG) excursion. Sodium-glucose cotransporter type 2 (SGLT2) is expressed in the kidney, where it reabsorbs 90% of filtered glucose. Thus, a dual SGLT1 and SGLT2 inhibition (compared with selective SGLT2 inhibition) could result in lower PPG and robust A1c reduction even in patients with reduced kidney function. Sotagliflozin is an oral potent dual inhibitor of the insulin-independent SGLT1 and SGLT2...
June 2018: Diabetes Technology & Therapeutics
Jinpeng Du, Chaojie Hu, Jie Bai, Miaomiao Peng, Qingbo Wang, Ning Zhao, Yu Wang, Guobin Wang, Kaixiong Tao, Geng Wang, Zefeng Xia
BACKGROUND: The unique effects of gastric resection after vertical sleeve gastrectomy (VSG) on type 2 diabetes mellitus remain unclear. This work aimed to investigate the effects of VSG on gastric leptin expression and intestinal glucose absorption in high-fat diet-induced obesity. METHODS: Male C57BL/6J mice were fed a high-fat diet (HFD) to induce obesity. HFD mice were randomized into VSG and sham-operation groups, and the relevant parameters were measured at 8 weeks postoperation...
June 18, 2018: Obesity Surgery
Markus Mühlemann, Daniela Zdzieblo, Alexandra Friedrich, Constantin Berger, Christoph Otto, Heike Walles, Hermann Koepsell, Marco Metzger
OBJECTIVES: Glycemic control by medical treatment represents one therapeutic strategy for diabetic patients. The Na+-d-glucose cotransporter 1 (SGLT1) is currently of high interest in this context. SGLT1 is known to mediate glucose absorption and incretin secretion in the small intestine. Recently, inhibition of SGLT1 function was shown to improve postprandial hyperglycemia. In view of the lately demonstrated SGLT1 expression in pancreatic islets, we investigated if loss of SGLT1 affects islet morphology and function...
July 2018: Molecular Metabolism
Halis Kaan Akturk, Amanda Rewers, Satish K Garg
PURPOSE OF REVIEW: To identify and evaluate the recent trials of sodium-glucose cotransporter 1 and 2 (SGLT1 and SGLT2, respectively) inhibitor use in patients with type 1 diabetes (T1D). SGLT-2 inhibitors have been approved by the Food and Drug Administration (FDA) and are effectively used in the treatment of type 2 diabetes (T2D). However, many studies (phase I-III) have validated their effects beyond improving glycemic control and have shown potential adjunctive use in adult patients with T1D treated with insulin therapy alone...
August 2018: Current Opinion in Endocrinology, Diabetes, and Obesity
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