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

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

Numerical study of anisotropic irreversible deposition of extended objects on a triangular lattice

The properties of the anisotropic random sequential adsorption (RSA) of objects of various shapes on a two-dimensional triangular lattice are studied numerically by means of Monte Carlo simulations. The depositing objects are formed by self-avoiding lattice steps. Anisotropy is introduced by positing unequal probabilities for orientation of depositing objects along different directions of the lattice. This probability is equa

Adsorption-desorption processes on discrete substrates-optimization of monolayer growth

Kinetics of the deposition process of dimers on a 1D lattice in the presence of desorption is studied by Monte Carlo method. The growth of the coverage θ(t) above the jamming limit to its steady-state value θ∞ is analyzed when desorption probability Pdes decreases both stepwise and linearly (continuously) over a certain time domain. We report a numerical evidence that the process of vibratory compaction of granular materials can be optimized by using a time dependent intensity of external excitations

Microelement content in infant formula, follow-on milk and cereal-based infant food

Usprkos preporuci o dojenju kao optimalnom obliku prehrane za dojenčad do 6. mjeseca života, više od 75% djece u Hrvatskoj biva hranjeno i zamjenskim industrijskim proizvodima. Cilj rada je ispitati udio mikroelemenata u početnoj i prijelaznoj hrani za dojenčad i hrani na bazi žitarica, dostupnima na tržištu Hrvatske, usporediti prikladnost proizvoda s obzirom na preporučeni dnevni unos, te s unosom pri prehrani isključivo majčinim mlijekom. Drugi cilj rada je ispitati utjecaj različitih temperatura vode za rehidraciju pripravaka na mikroelementarni sastav. Za kvantifikaciju je korištena multielementarna tehnika masene spektrometrije s induktivno spregnutom plazmom. Količine željeza, mangana i selena znatno variraju, dok je udio bakra i cinka prilično ujednačen. Prijelazno adaptirano mlijeko sadrži statistički značajno veće količine željeza od početnog adaptiranog mlijeka, dok prosječni dnevni unos adaptiranoga mlijeka i jednoga obroka hrane na bazi žitarica, osigurava 75% potreba dojenčadi za željezom tijekom drugih šest mjeseci života. Dnevni unos cinka premašuje prihvatljivi gornji dnevni unos, dok je dnevni unos mangana kod dojenčadi starosti 3 mjeseca za 40 puta veći od adekvatnoga. Trećina proizvoda ne osigurava niti polovinu preporučenog dnevnog unosa selena za dojenčad do 6 mjeseci. Statistički nije potvrđen utjecaj temperature na smanjenje količine mikroelementa.Contrary to the recommendation of breastfeeding as the best type of infant feeding up to 6 months of age, more than 75% of children are also being given industrial substitute products. The purpose of this paper is to examine the microelement contents in infant formula, adapted infant milk and cereal-based infant food available on the Croatian market; to compare the suitability of products concerning the recommended daily intake with the daily intake solely through breastfeeding. The other purpose is to examine the influence of different temperature values used for product rehydration The multielemental analytical technique of inductively coupled plasma mass spectrometry was used for quantification. The levels of iron, manganese and selenium vary considerably while the levels of copper and zinc are fairly uniform. Follow-on milk statistically contains considerably higher levels of iron than infant formula, while the average daily intake of follow-on milk and one meal of cereal-based infant food satisfies 75% of infant need for iron in the following six months. Daily intake of zinc exceeds the highest tolerable daily intake level while the daily intake of manganese in 3 months old infants is 40 times higher than what is considered tolerable. A third of the products do not ensure half of the recommended daily intake of selenium for infants up to 6 months old. The influence of temperature on the decrease of microelement levels has not been statistically confirmed

Uticaj Alternaria alternata na klijavost semena pšenice

Investigation of the effect Alternaria alternata on seed germination of wheat were tested on three varieties of Victory, Renaissance and NS 40 S. Seed germination is the ISTA rules, in order to elucidate the effect of primary and secondary infection pathogen A.alternata on seed natural and conditioned seeds were placed tests with seeds untreated, treated with NaOCl and fungicide Tycoon included. The high rate of seed germination was found in all three experiments. The correlation coefficient between secondary infection of seedlings with A.alternata and germination of wheat was -0.69 to -0.76, depending on the variety, indicating that the rate of infection has no significant effect on seed germination.Ispitivanje uticaja gljive Alternaria alternata na klijavost semena pšenice testirano je na tri sorte Pobeda, Renesansa i NS 40 S. Prema ISTA pravilima, a u cilju utvrđivanja uticaja primarne i sekundarne infekcije patogena A.alternata na klijavost naturalnog i dorađenog semenskog materijala, postavljeni su testovi sa semenom bez tretiranja, tretirano sa NaOCl i fungicidom Tycoon-om. Visoka stopa klijavosti semena je utvrđena u sva tri eksperimenta. Koeficijent korelacije između sekundarne zaraze klijanaca sa A.alternata i klijavosti semena pšenice iznosio je -0.69 do -0.76 u zavisnosti od sorte, ukazujući da infekcija nema značajan uticaj na klijavost semena

In female rats, ethylene glycol treatment elevates protein expression of hepatic and renal oxalate transporter sat-1 (Slc26a1) without inducing hyperoxaluria

Aim To investigate whether the sex-dependent expression of hepatic and renal oxalate transporter sat-1 (Slc26a1) changes in a rat model of ethylene glycol (EG)-induced hyperoxaluria. Methods Rats were given tap water (12 males and 12 females; controls) or EG (12 males and 12 females; 0.75% v/v in tap water) for one month. Oxaluric state was confirmed by biochemical parameters in blood plasma, urine, and tissues. Expression of sat-1 and rate-limiting enzymes of oxalate synthesis, alcohol dehydrogenase 1 (Adh1) and hydroxy-acid oxidase 1 (Hao1), was determined by immunocytochemistry (protein) and/or real time reverse transcription polymerase chain reaction (mRNA). Results EG-treated males had significantly higher (in μmol/L; mean ± standard deviation) plasma (59.7 ± 27.2 vs 12.9 ± 4.1, P < 0.001) and urine (3716 ± 1726 vs 241 ± 204, P < 0.001) oxalate levels, and more abundant oxalate crystaluria than controls, while the liver and kidney sat-1 protein and mRNA expression did not differ significantly between these groups. EG-treated females, in comparison with controls had significantly higher (in μmol/L) serum oxalate levels (18.8 ± 2.9 vs 11.6 ± 4.9, P < 0.001), unchanged urine oxalate levels, low oxalate crystaluria, and significantly higher expression (in relative fluorescence units) of the liver (1.59 ± 0.61 vs 0.56 ± 0.39, P = 0.006) and kidney (1.77 ± 0.42 vs 0.69 ± 0.27, P < 0.001) sat-1 protein, but not mRNA. The mRNA expression of Adh1 was femaledominant and that of Hao1 male-dominant, but both were unaffected by EG treatment. Conclusions An increased expression of hepatic and renal oxalate transporting protein sat-1 in EG-treated female rats could protect from hyperoxaluria and oxalate urolithiasis

Influence of blood count, cardiovascular risks, inherited thrombophilia, and JAK2 V617F burden allele on type of thrombosis in patients with Philadelphia chromosome negative myeloproliferative neoplasms

Introduction: Thrombosis is the most common complication in Philadelphia chromosome negative (Ph-) myeloproliferative neoplasms patients. ----- Patients and methods: In a cohort of 258 Ph- myeloproliferative neoplasm patients, the difference between patients with and without thrombosis was analyzed according to genetic thrombophilia factors, JAK2 V617F status and burden allele, blood count, cardiovascular risk factors and age. Patients were also divided in polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) subgroups as well as by the type of thrombosis. ----- Results: Analysis of cardiovascular risk factors regarding arterial thrombosis showed that PV patients with thrombosis had higher incidence of diabetes (P = .030), ET patients more often had hypertension (P = .003) and hyperlipidemia (P = .005), while PMF patients had hyperlipidemia (P = .046) and at least one cardiovascular risk factor (P = .044). Moreover, leukocytes > 18 × 109/L and V617F burden allele > 25.7% were statistically significantly different in PV patients (P = .019 and borderline significant at P = .055, respectively), while in ET patients leukocytes > 9.2 × 109/L (P 55 years were statistically significantly different (P = .002). PMF patients with V617F burden allele ≤ 34.8% were more prone to thrombosis (P = .032). When comparing patients with and without venous thrombosis, cutoff value of V617F burden allele > 90.4% was significant for PV patients with thrombosis (P = .036), as was > 56.7% for PMF patients with thrombosis (P = .046). Platelets ≤ 536 × 109/L and age at diagnosis > 54 years showed statistically significant difference for ET patients with thrombosis (P = .015 and P = .041, respectively). ----- Conclusion: On the basis of our results, a new scoring system for thrombosis risk in PV could be made, while PMF prognostic model may be expanded for better recognition of potential thrombotic risk factors

Cytogenetic Effects of Met-enkephalin (Peptid-M) on Human Lymphocytes

The structure, complementary structure and cytogenetic/proliferative effects of the Met-enkephalin on human peripheral blood lymphocytes were analyzed. Met-enkephalin, i.e. Peptid-M (LUPEX®), is a low molecular weight synthetic pentapeptide that corresponds to thymus Met-enkephalin. Its structure was examined by means of NMR spectroscopy. The influence of Met-enkephalin on in vitro normalization of chromosomally aberrant lymphocytes of patients suffering from different immune-mediated diseases, was analyzed by the sensitive cytogenetic tests for screening and detection of genome damages in human lymphocytes. The tests showed that in vitro stimulation of human lymphocytes with the Met-enkephalin led to dissapearance of different types of chromosome aberrations, reduction in the number of micronuclei, decrease in the frequency of sister chromatid exchange (SCE) and apoptosis as well as a cytostatic effect on mitosis cycles. They have also confirmed normalization of chromosomally aberrant cell findings in patients suffering from different immune-mediated diseases. These results suggest a possible role of Met-enkephalin (Peptid-M) in immunotherapy of different diseases which involve chromosomal aberrations as well as abnormal cell proliferation and offer new approaches to immunotherapy by the use of Peptid-M. Based on the molecular recognition theory and the SCA method, peptide complementary to Peptid-M was designed, synthesized and denoted Peptide-D. Peptide-D is a calpastatin fragment. Predicted ligand-receptor interaction between both peptides is confirmed by the results showing that Peptide-D blocked the Peptid-M induced lymphocyte proliferation in a dosedependent manner