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Eisuke Kato
Plant materials have been widely studied for their preventive and therapeutic effects for type 2 diabetes mellitus (T2DM) and obesity. The effect of a plant material arises from its constituents, and the study of these bioactive compounds is important to achieve a deeper understanding of its effect at the molecular level. In particular, the study of the effects of such bioactive compounds on various biological processes, from digestion to cellular responses, is required to fully understand the overall effects of plant materials in these health contexts...
February 17, 2019: Bioscience, Biotechnology, and Biochemistry
Lindsey Burggraaff, Paul Oranje, Robin Gouka, Pieter van der Pijl, Marian Geldof, Herman W T van Vlijmen, Adriaan P IJzerman, Gerard J P van Westen
Sodium-dependent glucose co-transporter 1 (SGLT1) is a solute carrier responsible for active glucose absorption. SGLT1 is present in both the renal tubules and small intestine. In contrast, the closely related sodium-dependent glucose co-transporter 2 (SGLT2), a protein that is targeted in the treatment of diabetes type II, is only expressed in the renal tubules. Although dual inhibitors for both SGLT1 and SGLT2 have been developed, no drugs on the market are targeted at decreasing dietary glucose uptake by SGLT1 in the gastrointestinal tract...
February 14, 2019: Journal of Cheminformatics
Theodosios D Filippatos, Angelos Liontos, Ioanna Papakitsou, Moses S Elisaf
Sodium-glucose co-transporter 2 (SGLT2) inhibitors inhibit glucose re-absorption in the proximal renal tubules. Two trials have shown significant reductions of cardiovascular (CV) events with empagliflozin and canagliflozin, which could not be attributed solely to their antidiabetic effects. Aim of the review is the critical presentation of suggested mechanisms/hypotheses for the SGLT2 inhibitors-cardioprotection. The search of the literature revealed many possible cardioprotective mechanisms, because SGLT2 inhibitors i) increase natriuresis and act as diuretics with unique properties leading to a reduction in preload and myocardial stretch (the diuretic hypothesis); ii) decrease blood pressure and afterload (the blood pressure lowering hypothesis), iii) favor the production of ketones, which can act as a "superfuel" in the cardiac and renal tissue (the "thrifty substrate" hypothesis), iv) improve many metabolic variables (the metabolic effects hypothesis), v) exert many anti-inflammatory effects (the anti-inflammatory effects hypothesis), vi) can act through the angiotensin II type II receptors in the context of simultaneous renin-angiotensin-aldosterone-system (RAAS) blockade leading to vasodilation and positive inotropic effects (the RAAS hypothesis), vii) directly decrease the activity of the upregulated in heart failure Na+ -H+ exchanger in myocardial cells leading to restoration of mitochondrial calcium handling in cardiomyocytes (the sodium hypothesis)...
February 13, 2019: Postgraduate Medicine
M Shibata, T Takahashi, T Kozakai, M Kakudo, S Kasuga, Y Azuma, Y Kurose
Intestinal glucose absorption varies with growth; however, the dynamics of these variations has not been yet fully elucidated in broiler chickens. The present study aimed to compare jejunal glucose uptake and maltose digestion in broilers of 2 different ages, i.e., 1- vs. 5 wk old. Oral D-maltose gavage, everted sac, and Ussing chamber experiments were carried out to investigate intestinal glucose absorption and mRNA expression of glucose-transport-related genes as well as jejunal maltase activity. Upon gavage, glucose concentrations peaked at 10 min post-administration in 1-wk-old chicks, while they peaked at 40 min in 5-wk-old chickens...
February 9, 2019: Poultry Science
Y L He, W Haynes, C D Meyers, A Amer, Y Zhang, P Chen, A E Mendonza, S Ma, W Chutkow, E Bachman
BACKGROUND: There is an unmet need for a safer and more effective treatment for obesity. This study assessed the effects of licogliflozin, a dual inhibitor of sodium-glucose co-transporter (SGLT) 1/2, on body weight, metabolic parameters and incretin hormones in patients with T2DM and/or obesity. METHODS: Patients with obesity (BMI 35-50kg/m2 ) were enrolled into a 12-week study (N=88; licogliflozin 150 mg q.d.). Patients with type-2 diabetes-mellitus (T2DM) were enrolled into a second, two-part study, comprising a single-dose cross-over (N=12; 2...
February 5, 2019: Diabetes, Obesity & Metabolism
Zhao Li, Vineet Agrawal, Mohun Ramratnam, Ravi K Sharma, Stephen D'Auria, Abigail Sincoular, Margurite Jakubiak, Meredith L Music, William J Kutschke, Xueyin N Huang, Lindsey Gifford, Ferhaan Ahmad
Aims: We previously reported that sodium-dependent glucose cotransporter 1 (SGLT1) is highly expressed in cardiomyocytes, and is further upregulated in ischemia. This study aimed to determine the mechanisms by which SGLT1 contributes to ischemia/reperfusion (I/R) injury. Methods and Results: Mice with cardiomyocyte-specific knockdown of SGLT1 (TGSGLT1-DOWN) and wildtype controls were studied. In vivo, the LAD coronary artery was ligated for 30 min and reperfused for 48 h...
February 4, 2019: Cardiovascular Research
Hiroomi Takayama, Masayuki Ohta, Kazuhiro Tada, Kiminori Watanabe, Takahide Kawasaki, Yuichi Endo, Yukio Iwashita, Masafumi Inomata
PURPOSE: Sleeve gastrectomy with duodenojejunal bypass (SG-DJB) is expected to become a popular procedure in East Asia. The aim of this study was to evaluate the effects of duodenojejunal bypass on glucose metabolism in a rat model of sleeve gastrectomy (SG). METHODS: Twenty-four Sprague-Dawley rats were divided into two groups: SG-DJB and SG alone. 6 weeks after surgery, body weight, feed intake, and metabolic parameters were measured, and oral glucose tolerance tests (OGTT) were performed...
January 31, 2019: Surgery Today
Jin-Oh Chung, So-Hee Yoo, Yeong-Eun Lee, Kwang-Soon Shin, Soo-Jin Yoo, Si-Hyun Park, Tae-Sik Park, Soon-Mi Shim
Green tea is being studied extensively for its postprandial hypoglycemic effect due to its abundant catechins. Along with catechins, water-soluble green tea polysaccharides are also currently gaining attention due to their natural hypoglycemic properties. The current study investigated the combinational effect of green tea extract (GTE) and crude green tea polysaccharides (CTP) in inhibiting glucose transport after digestion of rice starch, using an in vitro digestion model with a Caco-2 cell. Co-digestion of rice starch with GTE (16...
January 22, 2019: Food & Function
Kyu Hang Lee, Sang Don Lee, Namdu Kim, Kwee Hyun Suh, Young Hoon Kim, Sang Soo Sim
HM41322 is a novel oral sodium-glucose cotransporter (SGLT) 1/2 dual inhibitor. In this study, the in vitro and in vivo pharmacokinetic and pharmacologic profiles of HM41322 were compared to those of dapagliflozin. HM41322 showed a 10-fold selectivity for SGLT2 over SGLT1. HM41322 showed an inhibitory effect on SGLT2 similar to dapagliflozin, but showed a more potent inhibitory effect on SGLT1 than dapagliflozin. The maximum plasma HM41322 level after single oral doses at 0.1, 1, and 3 mg/kg were 142, 439, and 1830 ng/ml, respectively, and the T1/2 was 3...
January 2019: Korean Journal of Physiology & Pharmacology
Peter Cressey, John Reeve
Potential toxicity of cyanogenic glycosides arises from enzymatic degradation to produce hydrogen cyanide. Information on the metabolism of cyanogenic glycosides is available from in vitro, animal and human studies. In the absence of β-glucosidase enzymes from the source plant material, two processes appear to contribute to the production of cyanide from cyanogenic glycosides; the proportion of the glycoside dose that reaches the large intestine, where most of the bacterial hydrolysis occurs, and the rate of hydrolysis of cyanogenic glycosides to cyanohydrin and cyanide...
January 4, 2019: Food and Chemical Toxicology
Marina Subramaniam, Lynn P Weber, Matthew E Loewen
Electrogenic sodium dependent glucose transport along the length of the intestine was compared between the omnivorous Nile tilapia ( Oreochromis niloticus) and the carnivorous Rainbow trout ( Oncorhynchus mykiss) in Ussing chambers. In tilapia, a high-affinity, high-capacity (Ha/Hc) kinetic system accounted for the transport throughout the proximal intestine, mid-intestine, and hindgut segments. Similar dapagliflozin and phloridzin dihydrate inhibition across all segments support this homogenous Ha/Hc system throughout the tilapia intestine...
January 2, 2019: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
R Barekatain, G Nattrass, A J Tilbrook, K Chousalkar, S Gilani
Little is known about the effect of low-protein (LP) diets on intestinal barrier function and permeability. In the first part of this study, starting on day 9 of age, the growth performance of the birds fed 3 experimental diets in each phase of feeding (G/F: grower/finisher) was investigated. Three experimental diets were as follows: LP (170/150 g/kg CP) fortified with essential amino acids (EAA), standard protein (SP), (202/190 g/kg), and high protein (HP) (220/210 g/kg). LP and SP diets contained a similar level of EAA concentration, while the HP diet contained 10% above the Ross 308 specifications...
December 28, 2018: Poultry Science
Zichao Wang, Xiaoxiao Zhao, Xiaoying Liu, Wenbo Lu, Shutong Jia, Tingting Hong, Ruifang Li, Huiru Zhang, Lin Peng, Xiaobei Zhan
In current study, a polysaccharide (GPP) was successfully extracted from Gynostemma pentaphyllum herb. Monosaccharide composition of GPP was rhamnose, arabinose, galactose, glucose, xylose, mannose, galacturonic acid and glucuronic acid in a molar ratio of 4.11: 7.34: 13.31: 20.99: 1.07: 0.91: 4.75: 0.36. Molecular weight and polydispersity (Mw/Mn) of GPP were 4.070 × 104  Da and 1.037, respectively. Primary structure features of GPP were determined to be a polysaccharide by FT-IR and NMR. Fasting blood sugar of diabetic mice decreased from 17...
December 24, 2018: International Journal of Biological Macromolecules
Shoichi Kuroda, Yohei Kobashi, Takahiro Oi, Kenichi Kawabe, Fumiyasu Shiozawa, Lisa Okumura-Kitajima, Mami Sugisaki-Kitano, Fusayo Io, Koji Yamamoto, Hiroyuki Kakinuma
A new series of C-phenyl d-glucitol derivatives was designed and synthesized, and their SGLT1 inhibitory potency and absorbability were evaluated. We also investigated whether kidney drug retention could be avoided by creating molecules with different excretion pathways. To achieve a class of molecules with low absorption and that were excreted in bile, optimized synthesis was performed to bring the ClogP value and the topological polar surface area to within the appropriate ranges. Compounds 34d and 34j were poorly absorbed, but the absorbed compounds were mainly excreted in bile...
December 11, 2018: Bioorganic & Medicinal Chemistry
Faith A Omonijo, Shangxi Liu, Qianru Hui, Hua Zhang, Ludovic Lahaye, Jean-Christophe Bodin, Joshua Gong, Martin Nyachoti, Chengbo Yang
It is well known that essential oil thymol exhibits antibacterial activity. The protective effects of thymol on pig intestine during inflammation is yet to be investigated. In this study, an in vitro lipopolysaccharide (LPS)-induced inflammation model using IPEC-J2 cells was established. Cells were pre-treated with thymol for 1 h and then exposed to LPS for various assays. Interleukin 8 (IL-8) secretion, the mRNA abundance of cytokines, reactive oxygen species (ROS), nutrient transporters, and tight junction proteins was measured...
December 19, 2018: Journal of Agricultural and Food Chemistry
Agustin Gonzalez-Vicente, Pablo D Cabral, Nancy J Hong, Jessica Asirwatham, Fara Saez, Jeffrey L Garvin
Fructose consumption has increased due to widespread use of high-fructose corn syrup by the food industry. Renal proximal tubules are thought to reabsorb fructose. However, fructose reabsorption (Jfructose ) by proximal tubules has not yet been directly demonstrated, nor the effects of dietary fructose on Jfructose . This segment express sodium-glucose linked transporters (SGLTs) 1, 2, 4 and 5, and glucose transporters (GLUTs) 2 and 5. SGLT4 and 5 transport fructose but SGLT1 and 2 don't. Knocking out SGLT5 increases urinary fructose excretion...
December 19, 2018: American Journal of Physiology. Renal Physiology
Nan Wang, Shuai Li, Xiao-Chen Guo, Jun-Yan Li, Gui-Ping Ren, De-Shan Li
Fibroblast growth factor-21 (FGF-21), an endocrine hormone, is regarded as a therapeutic target for diabetes base on its potent effects on improving hyperglycemia. Sodium-dependent glucose cotransporter 1 (SGLT1) is mainly expressed in the small intestine (SI) for intestinal glucose absorption. It has been demonstrated that SGLT1 expression is increased in diabetes, which is thought to contribute to the rapidly rising postprandial blood glucose levels. Thus, we aim to examine whether FGF-21 regulates expression of intestinal SGLT1 in diabetes...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Nelson Andrade, Cláudia Silva, Fátima Martel
The pathogenesis of various gastrointestinal diseases, including gastrointestinal cancers and inflammatory bowel disease, is associated with increased oxidative stress levels. We aimed to investigate the effect of oxidative stress induced by tert -butylhydroperoxide (TBH) on the uptake of 3 H-deoxy-d-glucose (3 H-DG) and 14 C-fructose by the human intestinal Caco-2 cell line. TBH (500 μM; 24 h) increased lipid peroxidation (TBARS) levels and was not cytotoxic. TBH (500 μM; 24 h) increased uptake of both low (SGLT1-mediated) and high concentrations (SGLT1- and GLUT2-mediated) of 3 H-DG, but did not affect absorption of 14 C-fructose (GLUT2- and GLUT5-mediated)...
November 1, 2018: Toxicology Research
Hwee-Yeong Ng, Yueh-Ting Lee, Wei-Hung Kuo, Pei-Chen Huang, Wei-Chia Lee, Chien-Te Lee
BACKGROUND/AIMS: Hyperglycemia and hyperuricemia are two major disorders of Metabolic syndrome. Kidney plays a crucial role in maintaining the homeostasis of uric acid and glucose. The aim of the study was to examine the changes of renal glucose and uric acid transporters in animals with metabolic syndrome. METHODS: Sprague-Dawley rats were fed with high fructose diet (60%) for 3 months (FR-3) and 5 months (FR-5). At the end study, serum and urine biochemical data were compared...
December 7, 2018: Kidney & Blood Pressure Research
Paola Bisignano, Chiara Ghezzi, Hyunil Jo, Nicholas F Polizzi, Thorsten Althoff, Chakrapani Kalyanaraman, Rosmarie Friemann, Matthew P Jacobson, Ernest M Wright, Michael Grabe
Sodium-dependent glucose transporters (SGLTs) exploit sodium gradients to transport sugars across the plasma membrane. Due to their role in renal sugar reabsorption, SGLTs are targets for the treatment of type 2 diabetes. Current therapeutics are phlorizin derivatives that contain a sugar moiety bound to an aromatic aglycon tail. Here, we develop structural models of human SGLT1/2 in complex with inhibitors by combining computational and functional studies. Inhibitors bind with the sugar moiety in the sugar pocket and the aglycon tail in the extracellular vestibule...
December 7, 2018: Nature Communications
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