Glucose transporters in the mammalian blood cells

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

Glucose transporters in the mammalian blood cells

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

Morfološka raznolikost i odnosi populacija Scardinius dergle i Scardinius plotizza (Actinopteri; Cypriniformes) iz Hrvatske i Bosne i Hercegovine

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.Rod Scardinius (Cypriniformes, Actinopteri) pripada porodici Leuciscidae, potporodici Leuciscinae, a obuhvaća 10 vrsta. Do sada provedena filogenetička i morfometrijska istraživanja pokazala su veliku taksonomsku složenost unutar ovog roda. Stoga, cilj ovog istraživanja bio je utvrditi morfološku raznolikost i pridonijeti razjašnjenju taksonomskih odnosa i statusa S. dergle i S. plotizza. U svrhu ovog istraživanja uzorci S. dergle i S. plotizza prikupljeni su sa cijelog njihovog područja rasprostranjenosti u Hrvatskoj i Bosni i Hercegovini. Na svakoj jedinici izmjereno je 25 morfometrijskih značajki, koje su standardizirane alometrijskom pretvorbom i analizirane pomoću deskriptivne i inferencijalne statistike. Rezultati su pokazali značajne intra- i interspecifične razlike u ispitivanim morfometrijskim značajkama. Uz to, zabilježeno je zasebno grupiranje populacija svake vrste i djelomično preklapanje nekih populacija obje vrste, odražavajući njihov moguće odnose. Također, zabilježene merističke značajke su u skladu s determinističkim vrijednostima za većinu istraživanih populacija. Iako je ovo istraživanje dalo indikacije odnosa i statusa populacija S. dergle i S. plotizza, kako bi se potvrdili rezultati i utvrdio točan taksonomski status, filogenetički odnosi i genetska raznolikost ovih vrsta, potrebna su daljnja filogenetička istraživanja

FILAGGRIN GENE NULL-MUTATIONS AND ATOPIC DISEASES

Dosadašnja istraživanja pokazuju da su null-mutacije gena, odnosno gubitak funkcije gena koji kodira protein filagrin (FLG), čija je funkcija održavanje strukture i hidracije epidermisa, povezane s nastankom atopijskih poremećaja, ponajprije sa sindromom atopijskog ekcema/dermatitisa (AEDS). Sveukupno je dosad izolirano 40-tak različitih null-mutacija FLG čiji udio varira među svjetskim populacijama. U zapadnoj Europi i Sjevernoj Americi null-mutacije FLG su prisutne u 10% populacije bijele rase od čega su najčešće mutacije R501X i 2282del4. Rezultati objavljenih europskih studija ukazuju da rasprostranjenost mutacija R501X i 2282del4 FLG ovisi o geografskoj širini, tj. da postoji gradijent učestalosti navedenih mutacija od sjevera prema jugu. Koža nosioca null-mutacije FLG podložnija je utjecaju različitih štetnosti te poremećena kožna barijera uzrokovana mutacijama FLG može biti dostatna za razvoj nespecifi čnih kožnih simptoma povezanih s atopijskim i neatopijskim kožnim poremećajima. Epidemiološke studije ukazuju na povezanost null-mutacija FLG s AEDS, dok rezultati o povezanosti null-mutacija FLG s razvojem senzibilizacije na uobičajene inhalacijske alergene, razvojem rinitisa i astme neovisno o prisutnosti AEDS nisu jednoznačni. U hrvatskoj populaciji utvrđena je mala učestalost nullmutacija FLG (2,6 %), te one nisu potvrđene kao značajni etiološki čimbenici u pojavi atopije i atopijskih bolesti u ispitivanoj populaciji.Null-mutations which cause loss of function of the gene encoding filaggrin (FLG) have been strongly linked to the development of atopic disorders, predominantly atopic eczema/dermatitis syndrome (AEDS). Filaggrin plays a key role in epidermal barrier function by upholding epidermal structure and moisturization. Up to now, around 40 variants of FLG nullmutations have been genotyped among different world populations. FLG null-mutations are present in up to 10% of the Caucasian population in Western Europe and North America, with R05X and 2282del4 as the most common null-mutations. Epidemiological studies conducted in Europe indicate a latitude dependent distribution of common FLG null-mutations with a decreasing north-south gradient of R501X and 2282del4 mutation frequencies. FLG null-mutation carriers are prone to develop unspecific skin symptoms related to atopic and non-atopic skin disorders due to their defect of epidermal barrier function, which allows greater skin penetration of various hazards. Epidemiological studies indicate an association of FLG null-mutations with AEDS, whereas results regarding an association of FLG null-mutations with sensitization to common inhalant allergens and development of rhinitis and asthma are incoherent. A study conducted in Croatia found a low frequency of FLG null-mutations in general population (2.6%) and did not confi rm FLG null-mutations as an etiological factor for atopy and atopic disease in the studied population

Odnos ultrazvučnih parametara gustoće kostiju, plućne funkcije i indeksa tjelesne mase u zdrave studentske populacije

Low bone mineral density has been reported in paediatric and adult patients with different lung diseases, but limited data are available on the association between lung function and bone density in a healthy young population. We explored the predictors of association between bone mass and pulmonary function in healthy first-year university students, focusing on body mass index (BMI). In this cross-sectional study we measured bone density with ultrasound and lung function with spirometry in 370 university students (271 girls and 99 boys). Information on lifestyle habits, such as physical activity, smoking, and alcohol consumption were obtained with a questionnaire. All lung function and bone parameters were significantly higher in boys than in girls (P<0.001). Underweight students had a significantly lower forced vital capacity (FVC%) (P=0.001 girls; P=0.012 boys), while overweight students had a significantly higher FVC% than normal weight students (P=0.024 girls; P=0.001 boys). BMI significantly correlated with FVC% (P=0.001) and forced expiratory volume in 1 second (FEV1 %) in both genders (P=0.001 girls; P=0.018 boys) and with broadband ultrasound attenuation (BUA) in boys. There were no significant associations between any of the bone and lung function parameters either in boys or girls. The most important determinant of lung function and ultrasound bone parameters in our study population was body mass index, with no direct association between bone density and lung function.Rezultati istraživanja pokazali su da pedijatrijski i odrasli bolesnici s različitim plućnim bolestima mogu imati nisku mineralnu gustoću kostiju, međutim ograničeni podaci postoje o povezanosti plućne funkcije i gustoće kostiju u zdravoj mladoj populaciji. U ovom presječnom istraživanju analizirali smo čimbenike koji mogu utjecati na povezanost plućne funkcije i koštane gustoće u 370 zdravih studenata prve godine studija. Uz mjerenje visine i težine, ispitanicima je spirometrijski određena plućna funkcija, izmjerena mineralna gustoća kostiju ultrazvučnom metodom te su prikupljeni podaci o tjelesnoj aktivnosti, pušenju i unosu alkohola. Svi dobiveni pokazatelji plućne funkcije i mineralne gustoće kostiju bili su značajno veći u muških ispitanika u odnosu na djevojke (P<0,001). U odnosu na ispitanike s normalnom tjelesnom težinom, pothranjeni ispitanici imali su značajno manji forsirani vitalni kapacitet (FVC %) (P=0,001 djevojke; P=0,012 mladići), a ispitanici s prekomjernom težinom značajno veći FVC % (P=0,024 djevojke; P=0,001 mladići). Indeks tjelesne mase (ITM) u oba je spola značajno korelirao s FVC % (P=0,001) i s forsiranim ekspiratornim volumenom u prvoj sekundi (FEV1 %) (P=0,001 djevojke; P=0,018 mladići), kao i sa slabljenjem ultrazvučnog vala pri prolasku kroz kost (BUA) u mladića. Nije nađena značajna izravna povezanost između pokazatelja plućne funkcije i koštane gustoće. Regresijskom je analizom indeks tjelesne mase utvrđen kao najvažniji prediktor plućne funkcije i koštane gustoće u ispitanika obaju spolova

Prijenosnici natrija i glukoze: nove mete ciljanih terapija u liječenju raka?

Glucose, the key source of metabolic energy, is imported into cells by two categories of transporters: 1) facilitative glucose transporters (GLUTs) and 2) secondary active sodium-glucose cotransporters (SGLTs). Cancer cells have an increased demand for glucose uptake and utilisation compared to normal cells. Previous studies have demonstrated the overexpression of GLUTs, mainly GLUT1, in many cancer types. As the current standard positron emission tomography (PET) tracer 2-deoxy-2-(18F)fluoro-D-glucose (2-FDG) for imaging tumour cells via GLUT1 lacks in sensitivity and specificity, it may soon be replaced by the newly designed, highly sensitive and specific SGLT tracer α-methyl-4-(F-18)fluoro-4-deoxy-Dglucopyranoside (Me-4FDG) in clinical detection and tumour staging. This tracer has recently demonstrated the functional activity of SGLT in pancreatic, prostate, and brain cancers. The mRNA and protein expression of SGLTs have also been reported in colon/colorectal, lung, ovarian, head, neck, and oral squamous carcinomas. So far, SGLTs have been poorly investigated in cancer, and their protein expression and localisation are often controversial due to a lack of specific SGLT antibodies. In this review, we describe current knowledge concerning SGLT1 and SGLT2 (over)expression in various cancer types. The findings of SGLTs in malignant cells may help in developing novel cancer therapies with SGLT2 or SGLT1/SGLT2 inhibitors already used in diabetes mellitus treatment.Glukoza, glavni izvor metaboličke energije, ulazi u stanicu na dva načina: 1) olakšanom difuzijom pomoću prijenosnika glukoze GLUT i 2) sekundarno aktivnim prijenosom pomoću prijenosnika natrija i glukoze SGLT. Stanice raka imaju povećani unos glukoze u usporedbi s normalnim stanicama. Prethodna istraživanja pokazala su povećanu ekspresiju prijenosnika GLUT, uglavnom GLUT1, u mnogim tipovima raka. Radiofarmaceutik (engl. tracer) 2-deoksi-2-(18F) fluoro-D-glukoza (2-FDG), koji se koristi za detekciju tumorskih stanica putem GLUT1, nije dovoljno osjetljiv i specifičan. Uskoro bi mogao biti zamijenjen α-metil-4-(F-18) fluoro-4-deoksi-D-glukopiranozidom (Me-4FDG), novim i visoko osjetljivim, i specifičnim SGLT-radiofarmaceutikom u kliničkoj detekciji i određivanju stadija tumora. Tim je radiofarmaceutikom nedavno dokazana funkcionalna aktivnost prijenosnika SGLT u raku gušterače, prostate i mozga. Ekspresija mRNA i proteina SGLT također je pronađena u raku debelog crijeva, pluća, jajnika, glave, vrata i pločastih stanica usne šupljine. Prijenosnici SGLT nedovoljno su istraženi u raku, a njihova ekspresija i lokalizacija često su oprečne zbog nedostatka specifičnih SGLT-protutijela. U ovom preglednom radu opisujemo trenutačna znanja o povećanoj ekspresiji prijenosnika SGLT1 i SGLT2 u različitim tipovima raka. Spoznaje o ekspresiji i/ili lokalizaciji prijenosnika SGLT u malignim stanicama pomoći će u razvoju novih terapija u liječenju raka korištenjem već poznatih antidijabetika, SGLT2 ili SGLT1/SGLT2 inhibitora

Establishing paediatric reference intervals for thyroid function tests in Croatian population on the Abbott Architect i2000

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 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