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Glucose reabsorption

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https://www.readbyqxmd.com/read/29749749/recent-progress-of-sodium-glucose-transporter-2-inhibitors-as-potential-antidiabetic-agents
#1
Yajing Zhang, Huazhuo Ban, Runan Yu, Zhijian Wang, Dayong Zhang
SGLT2 inhibitors were promising and novel antidiabetic drugs which suppressed glucose reabsorption and increased urinary glucose exertion. This review paper are aimed to summarize the recent progress of SGLT2 inhibitors during the last 5 years. This paper first summarizes the information of SGLT2 inhibitors, including mechanism, evolution and then focuses on the recent efforts on structure-activity relationships and structural optimization of SGLT2 inhibitors. Finally, the corresponding clinical therapeutic efficacy and adverse drug reaction in patients with Type 2 diabetes are discussed in detail...
May 11, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29738274/renal-injury-in-seipin-deficient-lipodystrophic-mice-and-its-reversal-by-adipose-tissue-transplantation-or-leptin-administration-alone-adipose-tissue-kidney-crosstalk
#2
Xue-Jing Liu, Xiao-Yue Wu, Huan Wang, Su-Xia Wang, Wei Kong, Ling Zhang, George Liu, Wei Huang
Seipin deficiency is responsible for type 2 congenital generalized lipodystrophy with severe loss of adipose tissue (AT) and could lead to renal failure in humans. However, the effect of Seipin on renal function is poorly understood. Here we report that Seipin knockout (SKO) mice exhibited impaired renal function, enlarged glomerular and mesangial surface areas, renal depositions of lipid, and advanced glycation end products. Elevated glycosuria and increased electrolyte excretion were also detected. Relative renal gene expression in fatty acid oxidation and reabsorption pathways were impaired in SKO mice...
May 8, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29707805/intestinal-absorption-of-glucose-in-mice-as-determined-by-positron-emission-tomography
#3
Monica Sala-Rabanal, Chiara Ghezzi, Bruce A Hirayama, Vladimir Kepe, Jie Liu, Jorge R Barrio, Ernest M Wright
KEY POINTS: The goal was to determine the importance of the sodium glucose cotransporter SGLT1 and the glucose uniporter GLUT2 in intestinal glucose absorption during oral glucose tolerance tests (OGTTs) in mice. Glucose absorption was determined in mice using positron emission tomography and three non-metabolizable glucose probes: one specific for SGLTs, one specific for GLUTs, and one a substrate for both SGLTs and GLUTs. Absorption was determined in wild-type, Sglt1-/- , and Glut2-/- mice...
April 29, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29707091/sodium-glucose-cotransporter-2-inhibitors-reduce-prandial-insulin-doses-in-type-2-diabetic-patients-treated-with-the-intensive-insulin-therapy
#4
Mariko Hakoshima, Hidekatsu Yanai, Kouki Kakuta, Hiroki Adachi
Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are anti-diabetic drugs which improve blood glucose control by blocking reabsorption of glucose from the proximal tubule of kidney. Anti-atherosclerotic properties and cardiovascular protective effects of SGLT2i have been demonstrated by recent studies; however, the efficacy and safety of addition of SGLT2i to the intensive insulin therapy remain largely unknown. Methods: We retrospectively picked up patients hospitalized for treatment of type 2 diabetes, who had been treated by the intensive insulin therapy and whose treatment using by SGLT2i started during their hospitalization...
June 2018: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/29688190/-present-day-possibilities-of-non-invasive-control-over-microcirculation-and-metabolism-in-man
#5
A A Fedorovich, A G Bagdasarian, I G Uchkin, G N Soboleva, S A Boĭtsov
The main function of the microcirculatory bed consists in maintaining tissue homeostasis at an optimal level irrespective of the effect of various external and internal factors. Of all types of metabolism (diffusive, filtration-reabsorption and vesicular), directly dependent on the haemodynamic parameters is filtration-reabsorption metabolism which provides exchange of water, low-molecular-weight and water-soluble substances at the opposite to the heart «pole» of the cardiovascular system. The present study was aimed at testing a hypothesis that activation of metabolic processes in man would be accompanied by alterations in haemodynamic parameters which may be registered by means of modern non-invasive methods of examination, i...
2018: Angiologii︠a︡ i Sosudistai︠a︡ Khirurgii︠a︡, Angiology and Vascular Surgery
https://www.readbyqxmd.com/read/29663893/sglt-2-inhibition-novel-therapeutics-for-reno-and-cardioprotection-in-diabetes-mellitus
#6
Angus Gill, Stephen P Gray, Karin A Jandeleit-Dahm, Anna M D Watson
BACKGROUND: The sodium glucose co-transporter 2 (SGLT2) is primarily located within S1 of the renal proximal tubule being responsible for approximately 90% of glucose re-uptake in the kidney. Inhibition of SGLT2 is an exciting new pharmacological approach for the reduction of blood glucose in type 2 diabetic patients via inhibition of tubular glucose reabsorption. In addition to lowering glucose, this group of drugs has shown significant cardiovascular and renal protective effects. CONCLUSION: This review aims to outline the current state of preclinical research and clinical trials for different SGLT2 inhibitors and outline some of the proposed mechanisms of action, including possible effects on sympathetic nerve activity, which may contribute to the unexpected beneficial cardiovascular and reno-protective effects of this class of compounds...
April 17, 2018: Current Diabetes Reviews
https://www.readbyqxmd.com/read/29663292/the-potential-role-of-sglt2-inhibitors-in-the-treatment-of-type-1-diabetes-mellitus
#7
Hadi Fattah, Volker Vallon
Type 1 diabetes mellitus is a difficult disease to treat due to the relative paucity of therapeutic options other than injectable insulin. The latter, however, can induce hypoglycemia, which has been linked to enhanced cardiovascular risk. Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral anti-hyperglycemic medications that do not increase the hypoglycemia risk and are US Food and Drug Administration (FDA) approved in type 2 diabetes mellitus. SGLT2 inhibitors may also be of benefit in type 1 diabetic patients, in addition to insulin, although they have not yet been approved for this indication...
April 16, 2018: Drugs
https://www.readbyqxmd.com/read/29588466/canagliflozin-inhibits-interleukin-1%C3%AE-stimulated-cytokine-and-chemokine-secretion-in-vascular-endothelial-cells-by-amp-activated-protein-kinase-dependent-and-independent-mechanisms
#8
Sarah J Mancini, Daria Boyd, Omar J Katwan, Anastasiya Strembitska, Tarek A Almabrouk, Simon Kennedy, Timothy M Palmer, Ian P Salt
Recent clinical trials of the hypoglycaemic sodium-glucose co-transporter-2 (SGLT2) inhibitors, which inhibit renal glucose reabsorption, have reported beneficial cardiovascular outcomes. Whether SGLT2 inhibitors directly affect cardiovascular tissues, however, remains unclear. We have previously reported that the SGLT2 inhibitor canagliflozin activates AMP-activated protein kinase (AMPK) in immortalised cell lines and murine hepatocytes. As AMPK has anti-inflammatory actions in vascular cells, we examined whether SGLT2 inhibitors attenuated inflammatory signalling in cultured human endothelial cells...
March 27, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29544622/the-evolution-of-eccrine-sweat-glands-in-human-and-nonhuman-primates
#9
Andrew Best, Jason M Kamilar
Sweating is an unusual thermoregulatory strategy for most mammals, yet is critical for humans. This trait is commonly hypothesized to result from human ancestors moving from a forest to a warmer and drier open environment. As soft tissue traits do not typically fossilize, this idea has been difficult to test. Therefore, we used a comparative approach to examine 15 eccrine gland traits from 35 primate species. For each trait we measured phylogenetic signal, tested three evolutionary models to explain trait variation, and used phylogenetic models to examine how traits varied in response to climate variables...
April 2018: Journal of Human Evolution
https://www.readbyqxmd.com/read/29532519/contrasting-effects-on-the-risk-of-macrovascular-and-microvascular-events-of-antihyperglycemic-drugs-that-enhance-sodium-excretion-and-lower-blood-pressure
#10
REVIEW
M Packer
Three classes of anti-hyperglycaemic medications are distinguished by their urinary sodium excretion-enhancing and blood pressure-lowering actions: long-acting glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors. Yet, these drugs exert different effects on macrovascular risk. Glucagon-like peptide-1 receptor agonists reduce atherosclerotic thromboembolic events, but have little effect on heart failure; sodium-glucose co-transporter-2 inhibitors decrease the occurrence of heart failure, but have minimal effect on myocardial infarction and stroke; and dipeptidyl peptidase-4 inhibitors do not ameliorate either atherosclerotic thromboembolic events or heart failure...
June 2018: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/29510178/metformin-increases-urinary-sodium-excretion-by-reducing-phosphorylation-of-the-sodium-chloride-cotransporter
#11
Hiroko Hashimoto, Naohiro Nomura, Wakana Shoda, Kiyoshi Isobe, Hiroaki Kikuchi, Kouhei Yamamoto, Takuya Fujimaru, Fumiaki Ando, Takayasu Mori, Tomokazu Okado, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
OBJECTIVE: Metformin is an antidiabetic drug that is widely used to treat patients with diabetes mellitus. Recent studies have reported that treatment with metformin not only improved blood glucose levels but also reduced blood pressure. However, it remains unclear how metformin reduces blood pressure. We hypothesized that metformin affects sodium reabsorption in the kidneys. METHODS: Urinary sodium excretion and expression of renal sodium transporters were examined in 8-week-old male C57BL/6 mice with acute and chronic treatment of metformin...
March 3, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29491318/the-anticipated-renoprotective-effects-of-sodium-glucose-cotransporter-2-inhibitors
#12
Marie Ito, Tetsuhiro Tanaka
Sodium-glucose cotransporter 2 (SGLT2), which is specifically expressed on the apical side of proximal tubular cells, is involved in the reabsorption of most of the glucose filtered by the glomeruli, and its inhibitors are gaining publicity as potent antihyperglycemic drugs. In some clinical trials, SGLT2 inhibitors exerted cardiovascular and kidney protective effects, which appeared to be partly independent of the original glucose-lowering effect. SGLT2 inhibitors have both direct and indirect renoprotective effects...
February 28, 2018: Internal Medicine
https://www.readbyqxmd.com/read/29485012/sodium-glucose-cotransporter-2-inhibitors-potential-cardiovascular-and-mortality-benefits
#13
Lovic Dragan, Manolis Kallistratos, Constantinos Tsioufis, Charalampos Grassos, Dragan Djordjevic, Ivan Tasic, Athanasios Manolis, Andreas Pittaras
BACKGROUND: The impact of overt diabetes and poor glycemic control on the risk of cardiovascular disease is well established. Among patients with type 2 diabetes, several studies demonstrated a significant increase in coronary artery disease related death and cardiovacular events associated with HbA1c levels of greater than 7 % compared with lower levels. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a novel class of anti-diabetic drugs that lower blood glucose levels through the suppression of renal glucose reabsorption thereby promoting renal glucose excretion...
February 26, 2018: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/29485006/risks-associated-with-sglt2-inhibitors-an-overview
#14
Mahakpreet Singh, Anoop Kumar
Sodium glucose co-transport 2 inhibitors (SGLT2-i) are the new class of anti-diabetic medications which are the recently approved (2013) by FDA for the treatment of diabetes. These inhibitors block the SGLT2 protein which involved in glucose reabsorption from proximal renal tubule which results in increased glucose excretion and lower blood glucose levels. These inhibitors exert favourable effects beyond glucose control such as consistent body weight, blood pressure, and serum uric acid reductions. Canagliflozin, Dapagliflozin, and Empagliflozin belong to the class of SGLT2 inhibitors...
February 25, 2018: Current Drug Safety
https://www.readbyqxmd.com/read/29424089/cardiovascular-benefits-of-sglt2-inhibition-in-diabetes-and-chronic-kidney-diseases
#15
EDITORIAL
A T Layton, V Vallon
No abstract text is available yet for this article.
April 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29415819/a-new-class-of-drugs-for-heart-failure-sglt2-inhibitors-reduce-sympathetic-overactivity
#16
REVIEW
Motoaki Sano
Even in the presence of excess glucose, the proximal renal tubules continue to resorb more glucose. Sodium glucose cotransporter 2 (SGLT2) inhibitors are drugs that control this "greed" (H. Ito, Keio University, Japan). Negative feedback mechanisms maintain homeostasis for various physiological functions. However, there is no negative feedback mechanism for resorption of glucose by the proximal renal tubules. When food was scarce during human evolution, not limiting nutrient reabsorption was advantageous for survival, but the opposite is true in the era of satiation...
May 2018: Journal of Cardiology
https://www.readbyqxmd.com/read/29412124/sodium-glucoser-cotransporter-2-inhibitors-glucose-lowering-against-other-hypoglycemic-agents
#17
Konstantinos Avranas, Konstantinos Imprialos, Konstantinos Stavropoulos, Georgios Lales, Alexandos Manafis, Anastasia Skalkou, Lars Kihm
BACKGROUND: The treatment of diabetes remains over the decades challenging, even after the introduction of numerous novel drugs of different classes. Most patients with type 2 diabetes necessitate the combination of multiple agents and eventually use of insulin. The newest, and possibly with the most pleiotropic actions after metformin are the sodium-glucose cotransporter 2 inhibitors (SGLT-2i). This class has a unique mechanism inhibiting the glucose reabsorption in the proximal tubule of the kidney...
February 6, 2018: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/29412119/sodium-glucose-cotransporter-2-inhibitors-and-ischemic-stroke
#18
Dimitrios Milonas, Konstantinos Tziomalos
BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with substantially increased risk for cardiovascular events, including ischemic stroke. In turn, ischemic stroke represents a leading cause of mortality and long-term disability worldwide. The newest class of glucose-lowering agents is sodium-glucose cotransporter 2 (SGLT-2) inhibitors, which act through inhibition of glucose reabsorption in the kidney, resulting in glucose excretion without stimulating insulin release. Accumulating data suggests that these agents improve multiple risk factors for ischemic stroke except their glucose-lowering effect...
February 6, 2018: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/29402900/canagliflozin-an-sglt2-inhibitor-attenuates-the-development-of-hepatocellular-carcinoma-in-a-mouse-model-of-human-nash
#19
Kumiko Shiba, Kyoichiro Tsuchiya, Chikara Komiya, Yasutaka Miyachi, Kentaro Mori, Noriko Shimazu, Shinobu Yamaguchi, Naomi Ogasawara, Makoto Katoh, Michiko Itoh, Takayoshi Suganami, Yoshihiro Ogawa
Sodium glucose cotransporter 2 (SGLT2) inhibitors, an antidiabetic drug, promotes urinary excretion of glucose by blocking its reabsorption in the renal proximal tubules. It is unclear whether SGLT2 inhibition could attenuate nonalcoholic steatohepatitis (NASH) and NASH-associated hepatocellular carcinoma. We examined the preventive effects of an SGLT2 inhibitor canagliflozin (CANA) in Western diet (WD)-fed melanocortin 4 receptor-deficient (MC4R-KO) mice, a mouse model of human NASH. An eight-week CANA treatment attenuated hepatic steatosis in WD-fed MC4R-KO mice, with increased epididymal fat mass without inflammatory changes...
February 5, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29376471/emerging-roles-of-sglt2-inhibitors-in-obesity-and-insulin-resistance-focus-on-fat-browning-and-macrophage-polarization
#20
Liang Xu, Tsuguhito Ota
Obesity-associated low-grade inflammation underlies insulin resistance and associated metabolic comorbidities, such as type 2 diabetes (T2D) and nonalcoholic fatty liver disease. Excessive ectopic fat deposition in obesity causes disorders of energy homeostasis and low-grade chronic inflammation in metabolic tissues. In particular, obesity-induced recruitment and activation of adipose tissue macrophages play a key role in the pathogenesis of insulin resistance and T2D. Therefore, treatment options for energy metabolism and macrophage polarization in obese subjects are needed...
December 11, 2017: Adipocyte
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