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Glucose reabsorption

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https://www.readbyqxmd.com/read/29144539/model-based-evaluation-of-proximal-sodium-reabsorption-through-sglt2-in-health-and-diabetes-and-the-effect-of-inhibition-with-canagliflozin
#1
Jessica A Brady, K Melissa Hallow
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce glucose levels in diabetes by inhibiting renal glucose reabsorption in the proximal tubule (PT), resulting in urinary glucose excretion. A recent large cardiovascular outcomes trial suggested that the SGLT2i empagliflozin may also decrease risk of renal dysfunction. Because sodium (Na) and glucose reabsorption are coupled through SGLT2, it is hypothesized that the renal benefits may be derived from lowering Na reabsorption in the PT, which would lead to favorable renal hemodynamic changes...
November 16, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29114945/hyperglycemia-induced-by-chronic-i-p-and-oral-glucose-loading-leads-to-hypertension-through-increased-na-retention-in-proximal-tubule
#2
Selim Fakhruddin, Wael A Alanazi, Hussain N Alhamami, Karen P Briski, Keith E Jackson
Feeding animals glucose, fructose, sucrose, and fat-enriched diets can lead to diet-induced hyperglycemia, severity of which largely depends on type and concentration of nutrients used and length of dietary intervention. As a strategy of dietary intervention, we adopted glucose-enriched diet, drinking water, and intraperitoneal (i.p.) glucose injection at the dose previously determined to be effective to establish a sustained hyperglycemia over a period of 2 weeks. In our current study, we used 4 groups of Sprague Dawley rats: control, glucose-treated, glucose+tempol, and glucose+captopril-treated groups...
November 7, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/29109021/renal-organic-anion-transporters-in-drug-drug-interactions-and-diseases
#3
REVIEW
Xiaokui Huo, Kexin Liu
The kidney plays a vital role in maintaining systemic homeostasis. Active tubular secretion and reabsorption, which are mainly mediated by transporters, is an efficient mechanism for retaining glucose, amino acids, and other nutrients and for the clearance of endogenous waste products and xenobiotics. These substances are recognized by uptake transporters located in the basolateral and apical membranes of renal proximal tubule cells and are extracted from plasma and urine. Organic anion transporters (OATs) belong to the solute carrier (SLC) 22 superfamily and facilitate organic anions across the plasma membranes of renal proximal tubule cells...
November 8, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29108038/prepartum-daylight-exposure-increases-serum-calcium-concentrations-in-dairy-cows-at-the-onset-of-lactation
#4
R Özçelik, R M Bruckmaier, L E Hernández-Castellano
In dairy cows, hypocalcemia is caused by the sudden calcium demand by the mammary gland at the onset of lactation. Calcitriol (1,25-dihydroxy vitamin D; 1,25-VitD) increases the intestinal calcium absorption and the renal calcium reabsorption. Daylight contributes to the formation of 1,25-VitD, as it transforms 7-dehydrocholesterol into cholecalciferol, a 1,25-VitD precursor. Calving pens are usually set in quiet places where cows can stay calm and relaxed before parturition. However, those pens often have poor lighting conditions and therefore cows may become vitamin D deficient because of inadequate daylight exposure...
October 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/29081625/sodium-glucose-transporter-2-inhibitors-and-diabetic-ketoacidosis-in-three-patients-with-diabetes-underlying-causation
#5
Jordan L Kelley, Matthew Strum, Daniel M Riche, Andrew M Chandler
Sodium glucose transporter 2 inhibitors (SGLT2i) inhibit the reabsorption of glucose in the renal tubules reducing glycemia and increasing glucosuria. The increased glucosuria causes a shift in normal flora and colonization of pathogenic microorganisms leading to an increase in mycotic genital infections. Recent Food and Drug Administration reported cases of diabetic ketoacidosis (DKA) after initiation of SGLT2i probes the question of safety with such agents. The mechanisms of ketoacidosis and the breakdown of lipids are often misunderstood, and blame is placed on lack of insulin or on medications used to treat diabetes...
July 2017: Journal of Pharmacology & Pharmacotherapeutics
https://www.readbyqxmd.com/read/29038362/cdc42-activation-couples-fluid-shear-stress-to-apical-endocytosis-in-proximal-tubule-cells
#6
Sohinee Bhattacharyya, Frédéric G Jean-Alphonse, Venkatesan Raghavan, Jennifer C McGarvey, Youssef Rbaibi, Jean-Pierre Vilardaga, Marcelo D Carattino, Ora A Weisz
Cells lining the kidney proximal tubule (PT) respond to acute changes in glomerular filtration rate and the accompanying fluid shear stress (FSS) to regulate reabsorption of ions, glucose, and other filtered molecules and maintain glomerulotubular balance. Recently, we discovered that exposure of PT cells to FSS also stimulates an increase in apical endocytic capacity (Raghavan et al. PNAS, 111:8506-8511, 2014). We found that FSS triggered an increase in intracellular Ca(2+) concentration ([Ca(2+)]i) that required release of extracellular ATP and the presence of primary cilia...
October 2017: Physiological Reports
https://www.readbyqxmd.com/read/29035321/a-novel-multi-epitope-vaccine-based-on-urate-transporter-1-alleviates-streptozotocin-induced-diabetes-by-producing-anti-urat1-antibody-and-an-immunomodulatory-effect-in-c57bl-6j-mice
#7
Yanjie Ma, Huimin Cao, Zhixin Li, Jinzhi Fang, Xiaomin Wei, Peng Cheng, Rui Jiao, Xiaoran Liu, Ya Li, Yun Xing, Jiali Tang, Liang Jin, Taiming Li
Hyperuricemia (HUA) is related to diabetes. Uric acid-induced inflammation and oxidative stress are risk factors for diabetes and its complications. Human urate transporter 1 (URAT1) regulates the renal tubular reabsorption of uric acid. IA-2(5)-P2-1, a potent immunogenic carrier designed by our laboratory, can induce high-titer specific antibodies when it carries a B cell epitope, such as B cell epitopes of DPP4 (Dipeptidyl peptidase-4), xanthine oxidase. In this report, we describe a novel multi-epitope vaccine composing a peptide of URAT1, an anti-diabetic B epitope of insulinoma antigen-2(IA-2) and a Th2 epitope (P2:IPALDSLTPANED) of P277 peptide in human heat shock protein 60 (HSP60)...
October 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29031726/reduced-renal-sympathetic-nerve-activity-contributes-to-elevated-glycosuria-and-improved-glucose-tolerance-in-hypothalamus-specific-pomc-knockout-mice
#8
Kavaljit H Chhabra, Donald A Morgan, Benjamin P Tooke, Jessica M Adams, Kamal Rahmouni, Malcolm J Low
OBJECTIVE: Hypothalamic arcuate nucleus-specific pro-opiomelanocortin deficient (ArcPomc(-/-)) mice exhibit improved glucose tolerance despite massive obesity and insulin resistance. We demonstrated previously that their improved glucose tolerance is due to elevated glycosuria. However, the underlying mechanisms that link glucose reabsorption in the kidney with ArcPomc remain unclear. Given the function of the hypothalamic melanocortin system in controlling sympathetic outflow, we hypothesized that reduced renal sympathetic nerve activity (RSNA) in ArcPomc(-/-) mice could explain their elevated glycosuria and consequent enhanced glucose tolerance...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29030466/modulation-of-renal-glut2-by-the-cannabinoid-1-receptor-implications-for-the-treatment-of-diabetic-nephropathy
#9
Liad Hinden, Shiran Udi, Adi Drori, Asaad Gammal, Alina Nemirovski, Rivka Hadar, Saja Baraghithy, Anna Permyakova, Matan Geron, Merav Cohen, Sabina Tsytkin-Kirschenzweig, Yael Riahi, Gil Leibowitz, Yaakov Nahmias, Avi Priel, Joseph Tam
Altered glucose reabsorption via the facilitative glucose transporter 2 (GLUT2) during diabetes may lead to renal proximal tubule cell (RPTC) injury, inflammation, and interstitial fibrosis. These pathologies are also triggered by activating the cannabinoid-1 receptor (CB1R), which contributes to the development of diabetic nephropathy (DN). However, the link between CB1R and GLUT2 remains to be determined. Here, we show that chronic peripheral CB1R blockade or genetically inactivating CB1Rs in the RPTCs ameliorated diabetes-induced renal structural and functional changes, kidney inflammation, and tubulointerstitial fibrosis in mice...
October 13, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29020011/a-microfluidic-renal-proximal-tubule-with-active-reabsorptive-function
#10
Else M Vedula, José Luis Alonso, M Amin Arnaout, Joseph L Charest
In the kidney, the renal proximal tubule (PT) reabsorbs solutes into the peritubular capillaries through active transport. Here, we replicate this reabsorptive function in vitro by engineering a microfluidic PT. The microfluidic PT architecture comprises a porous membrane with user-defined submicron surface topography separating two microchannels representing a PT filtrate lumen and a peritubular capillary lumen. Human PT epithelial cells and microvascular endothelial cells in respective microchannels created a PT-like reabsorptive barrier...
2017: PloS One
https://www.readbyqxmd.com/read/28978534/nmr-spectroscopy-and-electron-microscopy-identification-of-metabolic-and-ultrastructural-changes-to-the-kidney-following-ischemia-reperfusion-injury
#11
Tafadzwa Chihanga, Qing Ma, Jenna D Nicholson, Hannah N Ruby, Richard E Edelmann, Prasad Devarajan, Michael A Kennedy
Cellular, molecular, and ultrastructural nephron changes associated with ischemia reperfusion injury-induced acute kidney injury (IRI-AKI) are not completely understood. Here, a multidisciplinary study was used to identify nephron changes in a mouse model of IRI-AKI. Histological analyses indicated distended Bowman's glomerular spaces and proximal and distal tubules. Increased filtrate volume in nephrons was caused by reduced water reabsorption by severely damaged proximal tubule brush borders and blocked flow of filtrate into collecting tubules by mucoprotein casts in distal tubules...
October 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28957470/treatment-of-severe-cholera-a-review-of-strategies-to-reduce-stool-output-and-volumes-of-rehydration-fluid
#12
Thomas Butler
Background: Severe cholera is a life-threatening illness of hypovolemic shock and metabolic acidosis due to rapid and profuse diarrheal fluid loss. Emergency life-saving therapy is i.v. saline, optionally supplemented with potassium and alkali to correct the fluid deficit, potassium losses and acidosis. After this initial rehydration, for the next 2 days ongoing stool losses are replaced with oral rehydration solution (ORS), which contains sodium chloride, potassium and alkali together with glucose or rice powder as a source of glucose to serve as a carrier for sodium...
May 1, 2017: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28938439/single-dose-metformin-enhances-bile-acid-induced-glucagon-like-peptide-1-secretion-in-patients-with-type-2-diabetes
#13
Andreas Brønden, Anders Albér, Ulrich Rohde, Jens F Rehfeld, Jens J Holst, Tina Vilsbøll, Filip K Knop
Context: Despite a position as the first-line pharmacotherapy in type 2 diabetes, the glucose-lowering mechanisms of metformin remain to be fully clarified. Gut-derived modes of action, including suppression of bile acid reabsorption and a resulting increase in glucagon-like peptide-1 (GLP-1) secretion, have been proposed. Objective: The aim of this study was to assess the GLP-1 secretory and glucometabolic effects of endogenously released bile, with and without concomitant single-dose administration of metformin in patients with type 2 diabetes...
November 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28912902/effects-of-dapagliflozin-on-body-composition-and-liver-tests-in-patients-with-nonalcoholic-steatohepatitis-associated-with-type-2-diabetes-mellitus-a-prospective-open-label-uncontrolled-study
#14
Hiroshi Tobita, Shuichi Sato, Tatsuya Miyake, Shunji Ishihara, Yoshikazu Kinoshita
BACKGROUND: Nonalcoholic steatohepatitis (NASH) is an active form of nonalcoholic fatty liver disease. Risk factors for NASH include type 2 diabetes mellitus (T2DM) and obesity. Sodium-glucose cotransporter 2 (SGLT2) inhibitors used to treat T2DM prevent glucose reabsorption in the kidney and increase glucose urinary excretion. Dapagliflozin is a potent, selective SGLT2 inhibitor that reduces hyperglycemia in patients with T2DM and has been demonstrated to reduce some complications associated with NASH in rodent models...
2017: Current Therapeutic Research, Clinical and Experimental
https://www.readbyqxmd.com/read/28870626/immunoreactivity-of-urate-transporters-glut9-and-urat1-is-located-in-epithelial-cells-of-the-choroid-plexus-of-human-brains
#15
Naoya Uemura, Ryuta Murakami, Yoichi Chiba, Ken Yanase, Ryuji Fujihara, Masato Mashima, Koichi Matsumoto, Machi Kawauchi, Gotaro Shirakami, Masaki Ueno
It has been suggested that urate plays a protective role in neurons, while hyperuricemia is correlated with atherosclerosis and cardiovascular disease. However, whether there is a system that directly transports urate into the brain remains to be clarified. In this study, the localization of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1), which are known to be representative reabsorptive urate transporters, was immunohistochemically examined in autopsied human brains. Immunoreactivity of GLUT9 was observed on the apical side of the cytoplasm of epithelial cells in the choroid plexus and in the cilia of ependymal cells of the human brain...
October 17, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28866383/renal-glucose-metabolism-in-normal-physiological-conditions-and-in-diabetes
#16
REVIEW
Mazen Alsahli, John E Gerich
The kidney plays an important role in glucose homeostasis via gluconeogenesis, glucose utilization, and glucose reabsorption from the renal glomerular filtrate. After an overnight fast, 20-25% of glucose released into the circulation originates from the kidneys through gluconeogenesis. In this post-absorptive state, the kidneys utilize about 10% of all glucose utilized by the body. After glucose ingestion, renal gluconeogenesis increases and accounts for approximately 60% of endogenous glucose release in the postprandial period...
August 7, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28861952/use-of-sodium-glucose-cotransporter%C3%A2-2-inhibitors-in-older-patients-with-type%C3%A2-2-diabetes-mellitus
#17
Takahiro Kambara, Rei Shibata, Hiroyuki Osanai, Yoshihito Nakashima, Hiroshi Asano, Kazuyoshi Sakai, Toyoaki Murohara, Masayoshi Ajioka
AIM: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic agents that act on the proximal renal tubules to lower blood glucose levels by inhibiting glucose reabsorption and promoting urinary glucose excretion. The present study assessed the long-term use of SGLT2 inhibitors in older patients with diabetes. METHODS: A total of 117 older patients with type 2 diabetes who were given SGLT2 inhibitors were enrolled from April 2014 to March 2016. RESULTS: The mean age of the patients was 73...
September 1, 2017: Geriatrics & Gerontology International
https://www.readbyqxmd.com/read/28854935/distribution-of-glucose-transporters-in-renal-diseases
#18
REVIEW
Leszek Szablewski
Kidneys play an important role in glucose homeostasis. Renal gluconeogenesis prevents hypoglycemia by releasing glucose into the blood stream. Glucose homeostasis is also due, in part, to reabsorption and excretion of hexose in the kidney.Lipid bilayer of plasma membrane is impermeable for glucose, which is hydrophilic and soluble in water. Therefore, transport of glucose across the plasma membrane depends on carrier proteins expressed in the plasma membrane. In humans, there are three families of glucose transporters: GLUT proteins, sodium-dependent glucose transporters (SGLTs) and SWEET...
August 31, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28843503/cyp7a1-is-continuously-increased-with-disrupted-fxr-mediated-feedback-inhibition-in-hypercholesterolemic-tallyho-jng-mice
#19
Eun-Ah Lee, Dong-In Lee, Hee-Yoen Kim, Sung-Hoon Ahn, Hye-Rim Seong, Won Hoon Jung, Ki Young Kim, Sungsub Kim, Sang Dal Rhee
TALLYHO/Jng (TH) mice reveal hypercholesterolemia at an early age before their plasma glucose levels have increased. The increased plasma cholesterol should be related to bile acids (BAs) metabolism, because cholesterol is the precursor of BAs and BAs change cholesterol metabolism in a feedback manner. We analyzed the BAs pool size, BAs composition, and expression levels of several proteins that have key roles in BAs synthesis, excretion, and reabsorption and compared them to those of C57BL/6 (B6) mice to study BAs metabolism in TH mice...
August 24, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28842746/expression-profiling-and-immunolocalization-of-na-d-glucose-cotransporter-1-in-mice-employing-knockout-mice-as-specificity-control-indicate-novel-locations-and-differences-between-mice-and-rats
#20
Ivana Vrhovac Madunić, Davorka Breljak, Dean Karaica, Hermann Koepsell, Ivan Sabolić
The expression and localization of sodium-D-glucose cotransporter SGLT1 (SLC5A1), which is involved in small intestinal glucose absorption and renal glucose reabsorption, is of high biomedical relevance because SGLT1 inhibitors are currently tested for antidiabetic therapy. In human and rat organs, detailed expression profiling of SGLT1/Sglt1 mRNA and immunolocalization of the transporter protein has been performed. Using polyspecific antibodies and preabsorption with antigenic peptide as specificity control, in several organs, different immunolocalizations of SGLT1/Sglt1 between human and rat were obtained...
August 26, 2017: Pflügers Archiv: European Journal of Physiology
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