T1R taste receptors are present throughout the gastrointestinal tract. Glucose absorption comprises active absorption via SGLT1 and facilitated absorption via GLUT2 in the apical membrane. Trafficking of apical GLUT2 is rapidly up-regulated by glucose and artificial sweeteners, which act through T1R2 + T1R3/α-gustducin to activate PLC β2 and PKC βII. We therefore investigated whether non-sugar nutrients are regulated by taste receptors using perfused rat jejunum in vivo. Under different conditions, we observed a Ca 2+ -dependent reciprocal relationship between the H + /oligopeptide transporter PepT1 and apical GLUT2, reflecting the fact that trafficking of PepT1 and GLUT2 to the apical membrane is inhibited and activated by PKC βII, respectively. Addition of l-glutamate or sucralose to a perfusate containing low glucose (20 mm) each activated PKC βII and decreased apical PepT1 levels and absorption of the hydrolysis-resistant dipeptide l-Phe( S)-l-Ala (1 mm), while increasing apical GLUT2 and glucose absorption within minutes. Switching perfusion from mannitol to glucose (75 mm) exerted similar effects. l-Glutamate induced rapid GPCR internalization of T1R1, T1R3 and transducin, whereas sucralose internalized T1R2, T1R3 and α-gustducin. We conclude that l-glutamate acts via amino acid and glucose via sweet taste receptors to coordinate regulation of PepT1 and apical GLUT2 reciprocally through a common enterocytic pool of PKC βII. These data suggest the existence of a wider Ca 2+ and taste receptor-coordinated transport network incorporating other nutrients and/or other stimuli capable of activating PKC βII and additional transporters, such as the aspartate/glutamate transporter, EAAC1, whose level was doubled by l-glutamate. The network may control energy supply.

Tryptophan degradation is an immune escape strategy shared by many tumors. However, cancer cells' compensatory mechanisms remain unclear. We demonstrate here that a shortage of tryptophan caused by expression of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) resulted in ATF4-dependent upregulation of several amino acid transporters, including SLC1A5 and its truncated isoforms, which in turn enhanced tryptophan and glutamine uptake. Importantly, SLC1A5 failed to be upregulated in resting human T cells kept under low tryptophan conditions but was enhanced upon cognate antigen T-cell receptor engagement. Our results highlight key differences in the ability of tumor and T cells to adapt to tryptophan starvation and provide important insights into the poor prognosis of tumors coexpressing IDO and SLC1A5.

BackgroundEffective fetal growth requires adequate maternal nutrition coupled to active transport of nutrients across the placenta, which, in turn requires ATP. Epidemiological and experimental evidence has shown that impaired maternal nutrition in utero results in an adverse postnatal phenotype for the offspring. Placental mitochondrial function might link maternal food intake to fetal growth since impaired placental ATP production, in response to poor maternal nutrition, could be a pathway linking maternal food intake to reduced fetal growth.MethodWe assessed the effects of maternal diet on placental water content, ATP levels and mitochondrial DNA (mtDNA) content in mice at embryonic (E) day 18 (E18). Females maintained on either low- (LPD) or normal- (NPD) protein diets were mated with NPD males.ResultsTo investigate the possibility of an underlying mitochondrial stress response, we studied cultured human trophoblast cells (BeWos). High throughput imaging showed that amino acid starvation induces changes in mitochondrial morphology that suggest stress-induced mitochondrial hyperfusion. This is a defensive response, believed to increase mitochondrial efficiency, that could underlie the increase in ATP observed in placenta.ConclusionsThese findings reinforce the pathophysiological links between maternal diet and conceptus mitochondria, potentially contributing to metabolic programming. The quiet embryo hypothesis proposes that pre-implantation embryo survival is best served by a relatively low level of metabolism. This may extend to post-implantation trophoblast responses to nutrition.

Background Home monitoring of urine protein is a critical component of disease management in childhood nephrotic syndrome. We describe the development of a novel mobile application, UrApp – Nephrotic Syndrome Manager, to aid disease monitoring. Methods UrApp was iteratively developed by a panel of two pediatric nephrologists and three research engineers from May 2017 to October 2018 for Apple iPhones. App features were devised by this expert panel to support urine monitoring and other home care tasks. Each feature and user-app interface element was systematically reviewed by the panel and iteratively redesigned to remove anticipated use issues. The app prototype was then refined based on two rounds of usability testing and semi-structured user interviews with a total of 20 caregivers and adolescent patients. The analytic function of UrApp in providing a camera read of the urine test strip was compared to a standard urinalysis machine using 88 patient urine samples and three iPhones, model versions 6S and 7. Exact agreement and weighted kappa were calculated between the UrApp and urinalysis machine reads. Results The final UrApp features include: camera read of a urine test strip; analysis of urine protein trends and alerts for new disease relapse/remission; transmission of urine protein results to providers; education materials; and medication reminders. During the second round of UrApp usability testing, all users were able to perform each of the functions without error and all perceived UrApp to be helpful and indicated that they would use UrApp. UrApp camera results had 97% exact agreement and an overall weighted kappa value of 0.91 (95% CI, 0.85–0.97) compared with standard urinalysis machine interpretation. Conclusions UrApp was specifically designed to support patients and families living with nephrotic syndrome by supporting disease monitoring and home management tasks. The technically innovative feature that makes this possible is the use of a smartphone camera to read the urine test strip. This novel tool has the potential to improve disease monitoring and reduce management burden. Electronic supplementary material The online version of this article (10.1186/s12911-019-0822-z) contains supplementary material, which is available to authorized users.

The sensitivity of radiolabeled bile acid (BA) binding and transport by basal plasma membrane (BPM) vesicles of human trophoblast to cholephilic organic anions (COAs) was studied by a rapid filtration technique. Glycocholate (GC) efflux from preloaded (15 microM GC) vesicles was investigated in the presence of 300 microM COAs at the trans-side of the membrane. Bilirubin (BR) diglucuronide and rose bengal induced a very strong transstimulating effect, whereas phalloidin and phenol red showed a negligible effect. This effect was from strong to moderate for indocyanine green > bromosulfophthalein (BSP) > or = fusidic acid > or = phenolphthalein > or = BR ditaurate > or = rifamycin SV > or = rifampicin. BSP-induced transstimulation was not additive to the "velocity effect" previously reported for bicarbonate. At the cis-side, BSP reduced the saturable component of taurocholate (TC) binding to BPM vesicles. BSP also induced a partial and mixed type of inhibition both in TC uptake [inhibitor constant (Ki) 227 microM] and efflux (Ki 209 microM). Two binding sites with overlapping specificity for BAs and other COAs are proposed in this carrier, the site for non-BA COA presumably corresponding to that for bicarbonate. In summary, the results indicate that several COAs can act as potential substrates for the BA carrier located at the BPM of human trophoblast. This stresses the "biliary-like" role of the placenta and suggests the possibility of developing new functional tests for this organ on the basis of fetal-maternal transfer of nontoxic cholephilic dyes.