Transporter 2 ^HOT^
The Billings are given the antidote. When Frank visits them in the hospital, before entering their room, he sees them with Jack, who is joking with them. He silently walks back to his car, where Tarconi is waiting. He drops his friend at the airport. Alone, Frank receives a call from a man who needs a transporter, to which he replies: "I'm listening."
Transporter 2
FIGURE 1. Structure of the substrate binding site of GlyT2 and comparison with other members of the NSS family. (A) GlyT2 homology model generated from the dDAT structure (PDB: 4M48). Residues that interact with glycine in the S1 site are represented as pink spheres. Sodium bound in Na3 of GlyT2 is shown as a yellow sphere. (B) Comparison of GlyT2 substrate site residues (pink sticks), LeuT (green sticks, PDB: 2A65) and NSS transporters with an outward facing atomic structure dDAT (yellow sticks, PDB: 4M48) and hSERT (teal sticks, PDB:5I73). W482 and S479 are highlighted as they restrict the size of the substrate site in GlyT2. The corresponding residues in LeuT, dDAT, and hSERT are labelled for comparison.
Register for alerts If you have registered for alerts, you should use your registered email address as your username Citation toolsDownload this article to citation manager Björn Pasternak senior researcher, Viktor Wintzell statistician, Mads Melbye professor, Björn Eliasson adjunct professor, Ann-Marie Svensson research adviser, Stefan Franzén senior statistician et al Pasternak B, Wintzell V, Melbye M, Eliasson B, Svensson A, FranzÃn S et al. Use of sodium-glucose co-transporter 2 inhibitors and risk of serious renal events: Scandinavian cohort study BMJ 2020; 369 :m1186 doi:10.1136/bmj.m1186 BibTeX (win & mac)Download
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Streptozocin (STZ) is used for treating both pancreatic (PanNET) and gastrointestinal (GI-NET) neuroendocrine tumors but its therapeutic efficacy is relatively low in GI-NETs. Therefore, it has become pivotal to select GI-NET patients who could benefit from STZ treatment. STZ is transported via the glucose transporter 2 (GLUT2) into the cells and the loss of O6-methylguanine DNA methyltransferase (MGMT) also increases its therapeutic efficacy. Therefore, GLUT2 high and MGMT low status could be the surrogate markers of STZ.
The therapeutic efficacy of STZ has been reported to be influenced by the status of both glucose transporter 2 (GLUT2) and O6-methylguanine-DNA methyltransferase (MGMT) in tumor cells [15, 16]. STZ is actively transported to β cells via GLUT2 in the pancreas [14]. GLUT2 is a low-affinity glucose transporter expressed in pancreatic islet cells and involved in insulin secretion [17]. In GI tract, GLUT2 is expressed in enteroendocrine L-cells in both small and large intestines and epithelial cells in small intestine [18, 19]. MGMT is an enzyme that repairs DNA modifications, consequently preventing carcinogenesis [20]. Because of its promoter methylation, the loss of MGMT was also reported to be correlated with increased frequency of p53 point mutations in astrocytoma [21] and associated with adverse clinical outcome in lung or biliary tract cancer patients [20, 22]. Therefore, among the patients with neuroendocrine neoplasms (NENs), MGMT promoter methylation is postulated to be detected more frequently in high grade NENs than low or intermediate grade NENs. In addition, the loss of MGMT in tumor cells, including pancreatic neuroendocrine neoplasms [23], was reported to increase the therapeutic efficacy of DNA-alkylating agents, including STZ [20]. Therefore, STZ could be effective on MGMT low and GLUT-2 high NEN patients. However, in-depth information is not necessarily available regarding GLUT2 and MGMT status, which could influence therapeutic efficacy, especially in GI-NEN patients, some of whom could possibly benefit from STZ therapy [6].
one of the great trashy overcooked sequels, this is totally statham's bad boys 2/man on fire, a golden-hour slice of excessive & sweaty miami mayhem, statham flipping cars in mid-air, beating up dudes with a water hose, bashing a dude with watermelons on his fists, riding a jet ski onto the road, killing a dude with a boat, fighting the big bad in zero-gravity while a shitty ps2-looking plane falls into the ocean... not a minute goes by in this without something crazy happening. 00s cinema in retrospect was a great period for mid-budget action ludicrousness, where CGI was new/cheap enough to get away with looking bad and the lovably garrish MTV/matrix stylistics hadn't yet fallen out of fashion. transporter 2 is a perfect example of fun filmmaking that we've lost in the age of mega-franchises and IP.
More and more evidence indicates sodium-glucose co-transporter 2 inhibitors (SGLT2is) may display clinical benefits for heart failure with preserved ejection fraction (HFpEF). However, the mechanisms of the action remain unclear.
In recent years, more and more evidence shows that hypoglycemic drugs also have cardiovascular benefits [10, 11]. Sodium-glucose cotransporter-2 inhibitors (SGLT2is), including empagliflozin, dapagliflozin, canagliflozin, and ertugliflozin, show a good prospect in the treatment of HF [12,13,14,15,16]. EMPEROR-Preserved demonstrated the clinical benefit of empagliflozin in patients with HFpEF with or without diabetes [12]. Dapagliflozin significantly improved patient-reported symptoms, physical limitations, and exercise function and was well tolerated in chronic HFpEF [13]. Canagliflozin reduced the risk of cardiovascular death or hospitalized HF [14] and improved Kansas City Cardiomyopathy Questionnaire Total Symptom Score [15] in HFpEF patients. Among patients with diabetes and atherosclerotic cardiovascular disease, another SGLT2i, ertugliflozin was non-inferior to placebo with respect to major adverse cardiovascular events [16]. Based on these high-quality clinical trial results, we can confirm that SGLT2is have a significant therapeutic effect on HFpEF. However, the internal biological mechanisms of SGLT2is for HFpEF are unknown.
Inhibitors of sodium-glucose co-transporter 2 (SGLT2) have immediate glucose-lowering effects by promoting urinary glucose excretion, without altering insulin level. Only a few studies have evaluated blood glucose dynamics in the early period after administration. The present retrospective study was designed to determine the immediate effects of SGLT2 inhibitors on blood glucose dynamics.
In this report, we examined counts of individuals with sodium-glucose co-transporter-2 (SGLT-2) inhibitor and sitagliptin dispensings in the Sentinel Distributed Database (SDD) along with baseline conditions and other medication use. The study period includes data from March 1, 2013 to June 30, 2018. We distributed this request to six Sentinel Data Partners on September 21, 2021.
The organic cation transporter 2 (OCT2) is expressed in plasma membranes of kidney and brain. Its transport mechanism and substrates are debated. We studied substrate-induced changes of electrical current with the patch clamp technique after expression of rat OCT2 in oocytes. Activation of current, corresponding to efflux, was observed for small organic cations, e.g. choline. In contrast, the bigger cations quinine and tetrabutylammonium elicited no change in current. However, transport of choline could be inhibited by applying quinine or tetrabutylammonium to the cytoplasmic side. Inhibition of organic cation efflux by quinine was competitive with substrates. Quinine at the inside also inhibited substrate influx from the outside. Current-voltage analysis showed that both maximal turnover and apparent affinity to substrates are voltage-dependent. Substrate-induced currents with organic cations on both membrane sides reversed as predicted from the Nernst potential. Our results clearly identify the electrochemical potential as driving force for transport at neutral pH and exclude an electroneutral H(+)/organic cation(+) exchange. We suggest the existence of an electroneutral organic cation(+) exchange and propose a model for a carrier-type transport mechanism. 041b061a72