In enterocytes, protein RS1 (RSC1A1) mediates an increase of glucose absorption after ingestion of glucose-rich food via upregulation of Na+-d-glucose cotransporter SGLT1 in the brush-border membrane ...(BBM). Whereas RS1 decelerates the exocytotic pathway of vesicles containing SGLT1 at low glucose levels between meals, RS1-mediated deceleration is relieved after ingestion of glucose-rich food. Regulation of SGLT1 is mediated by RS1 domain RS1-Reg, in which Gln-Ser-Pro (QSP) is effective. In contrast to QSP and RS1-Reg, Gln-Glu-Pro (QEP) and RS1-Reg with a serine to glutamate exchange in the QSP motif downregulate the abundance of SGLT1 in the BBM at high intracellular glucose concentrations by about 50%. We investigated whether oral application of QEP improves diabetes in db/db mice and affects the induction of diabetes in New Zealand obese (NZO) mice under glucolipotoxic conditions. After 6-day administration of drinking water containing 5 mM QEP to db/db mice, fasting glucose was decreased, increase of blood glucose in the oral glucose tolerance test was blunted, and insulin sensitivity was increased. When QEP was added for several days to a high fat/high carbohydrate diet that induced diabetes in NZO mice, the increase of random plasma glucose was prevented, accompanied by lower plasma insulin levels. QEP is considered a lead compound for development of new antidiabetic drugs with more rapid cellular uptake. In contrast to SGLT1 inhibitors, QEP-based drugs may be applied in combination with insulin for the treatment of type 1 and type 2 diabetes, decreasing the required insulin amount, and thereby may reduce the risk of hypoglycemia.
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•Antioxidants melatonin and resveratrol may act as anti-aging compounds.•Male and female rats drank melatonin or resveratrol solutions for 9 or 21 months.•Body mass, and various ...parameters in blood cells and plasma were determined.•With aging, body mass increased in both sexes, and plasma testosterone decreased in males.•The pattern of all parameters remanied unchaged in rats treated with antioxidants.
Aging-related impaired body structure and functions may be, at least partially, caused by elevated oxidative stress. Melatonin (MEL) and resveratrol (RSV) may act as antioxidant and anti-aging compounds, but these actions in experimental animals and humans are controversial. Herein, a rat model of aging was used to study the long-term sex-related effects of MEL and RSV treatment on body mass and blood/plasma parameters of DNA damage, oxidative status (glutathione and malondialdehyde levels), and concentrations of sex hormones. Starting from the age of 3mo, for the next 9mo or 21mo male and female Wistar rats (n = 4–7 per group) were given water to drink (controls) or 0.1 % ethanol in water (vehicle), or MEL or RSV (each 10 mg/L vehicle). DNA damage in whole blood cells was tested by comet assay, whereas in plasma, glutathione, malondialdehyde, and sex hormones were determined by established methods. Using statistical analysis of data by ANOVA/Scheffe post hoc, we observed a similar sex- and aging-dependent rise of body mass in both sexes and drop of plasma testosterone in control and vehicle-treated male rats, whose pattern remained unaffected by MEL and RSV treatment. Compared with controls, all other parameters remained largely unchanged in aging and differently treated male and female rats. We concluded that the sex- and aging-related pattern of growth and various blood parameters in rats were not affected by the long-term treatment with MEL and RSV at the estimated daily doses (300−400 μg/kg b.m.) that exceed usual moderate consumption in humans.
Evaluation of thyroid function is often requested and therefore defining paediatric reference intervals (RIs) is of vital importance. Currently, there is a distinct lack of paediatric RIs for thyroid ...function tests in Croatia. Thus, we established RIs for thyroid stimulating hormone (TSH), total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3) and free thyroxine (FT4) in the Croatian paediatric population.
Reference intervals were calculated from 397 apparently healthy children, aged from 2 days to < 19 years. Serum samples were analysed for thyroid function tests on the Abbott Architect i2000. Age- and sex-specific 95% RIs with 90% confidence intervals were established according to Clinical and Laboratory Standards Institute guidelines. To express the magnitude of sex and age variation, standard deviation ratio (SDR) was calculated using two-level nested ANOVA. The criterion for considering partitioning reference values was set to SDR > 0.3.
All thyroid function tests required age partitioning, confirmed by SDR above 0.3. There was no need for sex partitioning, confirmed by SDR below 0.3. Still, FT3 was partitioned due to visually noticeable sex related difference for the oldest group (12 years to < 19 years).
This is the first study to establish RIs for thyroid function tests in the Croatian paediatric population. We propose RIs for widely used Abbott platform, thus giving laboratories method- and population-specific paediatric RIs for thyroid function tests that should improve clinical test interpretation.
Cellular glucose uptake may involve either non-concentrative glucose carriers of the GLUT family or Na+-coupled glucose-carrier SGLT1, which accumulates glucose against glucose gradients and may thus ...accomplish cellular glucose uptake even at dramatically decreased extracellular glucose concentrations. SGLT1 is not only expressed in epithelia but as well in tumour cells and immune cells. Immune cell functions strongly depend on their metabolism, therefore we hypothesized that deficiency of SGLT1 modulates the defence against bacterial infection. To test this hypothesis, we infected wild type mice and gene targeted mice lacking functional SGLT1 with Listeria monocytogenes.
SGLT1 deficient mice and wild type littermates were infected with 1x104 CFU Listeria monocytogenes intravenously. Bacterial titers were determined by colony forming assay, SGLT1, TNF-α, IL-6 and IL-12a transcript levels were determined by qRT-PCR, as well as SGLT1 protein abundance and localization by immunohistochemistry.
Genetic knockout of SGLT1 (Slc5a1-/- mice) significantly compromised bacterial clearance following Listeria monocytogenes infection with significantly enhanced bacterial load in liver, spleen, kidney and lung, and significantly augmented hepatic expression of TNF-α and IL-12a. While all wild type mice survived, all SGLT1 deficient mice died from the infection.
SGLT1 is required for bacterial clearance and host survival following murine Listeria infection.
Genus Scardinius (Cypriniformes, Actinopteri) belongs to the family Leuciscidae, subfamily Leuciscinae, and it includes 10 species. Phylogenetic and morphometric research conducted so far have shown ...a great taxonomic complexity within this genus. Therefore, the aim of this research was to determine the morphological diversity and contribute to the clarification of taxonomic relationships and status of S. dergle and S. plotizza. For the purpose of this research specimens of S. dergle and S. plotizza were collected from their whole distribution area in Croatia and Bosnia and Herzegovina. On each individual 25 morphometric characters were measured, standardized with allometric conversion and analysed using descriptive and inferential statistics. Results showed significant intra- and interspecific differences in investigated morphometric characters. In addition, distinct grouping of populations of each species and partial overlapping of some populations of both species was recorded, reflecting their possible relationships. Also, investigated meristic characters showed accordance with deterministic values for most investigated populations. Although this research has given indications of relationships and the status of populations of S. dergle and S. plotizza, in order to confirm the results and determine the exact taxonomic status, phylogenetic relationships and genetic diversity of these species, further phylogenetic research is needed.
Embryo implantation requires a hospitable uterine environment. A key metabolic change that occurs during the peri-implantation period, and throughout early pregnancy, is the rise in endometrial ...glycogen content. Glycogen accumulation requires prior cellular uptake of glucose. Here we show that both human and murine endometrial epithelial cells express the high affinity Na
-coupled glucose carrier SGLT1. Ussing chamber experiments revealed electrogenic glucose transport across the endometrium in wild type (Slc5a1
) but not in SGLT1 deficient (Slc5a1
) mice. Endometrial glycogen content, litter size and weight of offspring at birth were significantly lower in Slc5a1
mice. In humans, SLC5A1 expression was upregulated upon decidualization of primary endometrial stromal cells. Endometrial SLC5A1 expression during the implantation window was attenuated in patients with recurrent pregnancy loss when compared with control subjects. Our findings reveal a novel mechanism establishing adequate endometrial glycogen stores for pregnancy. Disruption of this histiotrophic pathway leads to adverse pregnancy outcome.
The Danube barbel,
Barbus balcanicus
is small rheophilic freshwater fish, belonging to the genus
Barbus
which includes 23 species native to Europe. In Croatian watercourses, three members of the ...genus
Barbus
are found,
B. balcanicus
,
B. barbus
and
B. plebejus
, each occupying a specific ecological niche. This study examined cytochrome
b
(cyt
b
), a common genetic marker used to describe the structure and origin of fish populations to perform a phylogenetic reconstruction of the Danube barbel. Two methods of phylogenetic inference were used: maximum parsimony (MP) and maximum likelihood (ML), which yielded well supported trees of similar topology. The Median joining network (MJ) was generated and corroborated to show the divergence of three lineages of
Barbus balcanicus
on the Balkan Peninsula: Croatian, Serbian and Macedonian lineages that separated at the beginning of the Pleistocene. Croatian lineage of
B. balcanicus
shows a uniform structure with many recently diverged haplotypes, which was further supported by the star-like shape of the MJ network. Effective size estimates were obtained for populations inhabiting separate river catchments and the results imply the good reproductive potential of
Barbus balcanicus
in Croatia, which is in positive correlation with the overall high genetic diversity calculated for its populations. Nevertheless, population sizes of several population seem to be reduced as a consequence of habitat degradation and fragmentation.
Le barbeau du Danube,
Barbus balcanicus
, est un petit poisson d'eau douce rhéophile, appartenant au genre
Barbus
qui comprend 23 espèces indigènes d'Europe. Dans les cours d'eau croates, on trouve trois membres du genre
Barbus
,
B. balcanicus
,
B. barbus
et
B. plebejus
, chacun occupant une niche écologique spécifique. Cette étude a examiné le cytochrome
b
(cyt
b
), un marqueur génétique commun utilisé pour décrire la structure et l'origine des populations de poissons afin d'effectuer une reconstruction phylogénétique du barbeau du Danube. Deux méthodes d'inférence phylogénétique ont été utilisées: la parcimonie maximale (MP) et la probabilité maximale (ML), qui ont permis d'obtenir des arbres bien étayés et de topologie similaire. Le réseau d'assemblage médian (MJ) a été généré et validé pour montrer la divergence de trois lignées de
Barbus balcanicus
dans la péninsule balkanique: les lignées croate, serbe et macédonienne qui se sont séparées au début du Pléistocène. La lignée croate de
B. balcanicus
présente une structure uniforme avec de nombreux haplotypes récemment divergents, qui a été renforcée par la forme étoilée du réseau MJ. Des estimations de taille effective ont été obtenues pour des populations vivant dans des bassins hydrographiques séparés et les résultats impliquent le bon potentiel reproductif de
Barbus balcanicus
en Croatie, qui est en corrélation positive avec la diversité génétique globale élevée calculée pour ses populations. Néanmoins, la taille de plusieurs populations semble être réduite en raison de la dégradation et de la fragmentation de l'habitat.
Glucose is the main source of metabolic energy for various cellular functions,
and thus plays a central role in supporting intermediary metabolism
and cellular homeostasis. Since plasma membrane is ...impermeable to glucose,
its cellular uptake is mediated by two distinct processes via specific glucose
transporter proteins that belong to the family of solute carriers (SLC); the
SLC2 family members, GLUTs (glucose transporters), are sodium-independent
facilitators of the glucose transport, whereas the SLC5 family members,
SGLTs (sodium and glucose transporters) mediate the secondary-active sodium-
glucose cotransport. Until now, 14 GLUTs and 12 SGLTs isoforms have
been identified in humans of which 5 GLUTs and none SGLTs were detected
in the mammalian blood cells. Detailed physiological function, precise
mechanism of transport, substrates affinity, exact three-dimensional structures,
and a precise tissue distribution of most GLUTs in various mammalian
organs, including blood, have been poorly explored. In this review we
will focus on GLUTs in the mammalian blood cells, where the data on their
expression and functional roles are contradictory or largely missing. Since
many GLUTs are associated with diabetes, and are up-regulated in cancers,
it is undoubtedly important to further investigate GLUTs expression in different
organs/tissues, including the blood cells. Understanding the complexity
of glucose homeostasis that includes knowledge about tissue distribution and
function of GLUTs, as well as the signaling pathways that regulate glucose
metabolism, may help to develop new therapeutic strategies to target specific
diseases, such as diabetes mellitus, some autoimmunity diseases, and cancer.
In the mammalian kidney, nonglycosylated and glycosylated forms of aquaporin protein 1 (AQP1) coexist in the luminal and basolateral plasma membranes of proximal tubule and descending thin limb. ...Factors that influence AQP1 expression in (patho)physiological conditions are poorly known. Thus far, only angiotensin II and hypertonicity were found to upregulate AQP1 expression in rat proximal tubule in vivo and in vitro (Bouley R, Palomino Z, Tang SS, Nunes P, Kobori H, Lu HA, Shum WW, Sabolic I, Brown D, Ingelfinger JR, Jung FF. Am J Physiol Renal Physiol 297: F1575-F1586, 2009), a phenomenon that may be relevant for higher blood pressure observed in men and male experimental animals. Here we investigated the sex-dependent AQP1 protein and mRNA expression in the rat kidney by immunochemical methods and qRT-PCR in tissue samples from prepubertal and intact gonadectomized animals and sex hormone-treated gonadectomized adult male and female animals. In adult rats, the overall renal AQP1 protein and mRNA expression was ∼80% and ∼40% higher, respectively, in males than in females, downregulated by gonadectomy in both sexes and upregulated strongly by testosterone and moderately by progesterone treatment; estradiol treatment had no effect. In prepubertal rats, the AQP1 protein expression was low compared with adults and slightly higher in females, whereas the AQP1 mRNA expression was low and similar in both sexes. The observed differences in AQP1 protein expression in various experiments mainly reflect changes in the glycosylated form. The male-dominant expression of renal AQP1 in rats, which develops after puberty largely in the glycosylated form of the protein, may contribute to enhanced fluid reabsorption following the androgen- or progesterone-stimulated activities of sodium-reabsorptive mechanisms in proximal tubules.
Chloride/formate exchanger (CFEX; SLC26A6) mediates oxalate transport in various mammalian organs. Studies in Cfex knockout mice indicated its possible role in development of male-dominant ...hyperoxaluria and oxalate urolithiasis. Rats provide an important model for studying this pathophysiological condition, but data on Cfex (rCfex) localisation and regulation in their organs are limited. Here we applied the RT-PCR and immunochemical methods to investigate rCfex mRNA and protein expression and regulation by sex hormones in the pancreas, small intestine, liver, and kidneys from intact prepubertal and adult as well as gonadectomised adult rats treated with sex hormones. rCfex cDNA-transfected HEK293 cells were used to confirm the specificity of the commercial anti-CFEX antibody. Various biochemical parameters were measured in 24-h urine collected in metabolic cages. rCfex mRNA and related protein expression varied in all tested organs. Sex-independent expression of the rCfex protein was detected in pancreatic intercalated ducts (apical domain), small intestinal enterocytes (brush-border membrane; duodenum > jejunum > ileum), and hepatocytes (canalicular membrane). In kidneys, the rCfex protein was immunolocalised to the proximal tubule brush-border with segment-specific pattern (S1=S2<S3), and both rCfex mRNA and protein expression exhibited male-dominant sex differences driven by stimulatory effects of androgens after puberty. However, urinary oxalate excretion was unrelated to renal rCfex protein expression. While the effect of male-dominant expression of rCfex in renal proximal tubules on urine oxalate excretion remains unknown, its expression in the hepatocyte canalicular membrane may be a pathway of oxalate elimination via bile.
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