Putative tissue location and function of the SLC5 family member SGLT3

NEW FINDINGS: What is the topic of this review? This review summarizes the evidence on the localization, electrophysiological properties, agonist specificity and putative physiological role of sodium-glucose transporter 3 (SGLT3). What advances does it highlight? Published information is reviewed in some detail by comparing human and rodent isoforms, as well as advances in testing hypotheses for the physiological role of SGLT3 as a glucose sensor or incretin release mediator. We provide a critical overview of available published data and discuss a putative functional role for SGLT3 in human and mouse physiology. Sodium-glucose transporter 3 (SGLT3) has attracted interest because of its putative role as a glucose sensor, rather than a sugar transporter, in contrast to its co-family members SGLT1 and SGLT2. Significant progress has been made in characterizing the electrophysiological properties in vitro of the single human SGLT3 isoform and the two mouse isoforms, SGLT3a and SGLT3b. Although early reports indicated SGLT3 expression in the small intestinal myenteric and submucosal neurones, hypothalamic neurones, portal vein and kidney, a lack of reliable antibodies has left unanswered its exact tissue and cellular localization. Several hypotheses for a role of SGLT3 in glucose sensing, gastric emptying, glucagon-like peptide-1 release and post-Roux-en-Y gastric bypass remodelling have been explored, but so far there is only limited and indirect supportive evidence using non-specific agonists/antagonists, with no firm conclusions. There are no published or available data in knockout animals, and translation is difficult because of its different isoforms in human versus rodent, as well as a lack of selective agonists or antagonists, all of which make SGLT3 challenging to study. However, its unique electrophysiological properties, ubiquitous expression at the mRNA level, enrichment in the small intestine and potential, but uncertain, physiological role demand more attention. The purpose of this overview and review of SGLT3 biology is to provide an update, highlight the gaps in our knowledge and try to signpost potential ways forward to define its likely function in vivo

Stratigraphic position of alkaline volcanic rocks in the autochthonous cover of the High-Tatric Unit (Western Tatra Mts., Central Western Carpathians, Slovakia)

Biostratigraphic investigations of carbonate strata that sandwich volcanic rocks and studies of the volcanic rocks were made along five composite lithological sections across the Upper Jurassic-Lower Cretaceous carbonate rocks of autochthonous cover of the High-Tatric Unit in the Osobitá peak area of the Western Tatra Mts. A carbonate microbreccia that consists almost exclusively of limestone clasts containing calpionellids occurs immediately below the volcanics. The youngest identified microfossil Calpionella elliptica Cadisch in the individual limestone clasts showed the age of breccia formation to be younger than late Early-early Middle Berriasian. The volcanic rocks are overlain by the Osobitá Limestone Formation, which in the lowermost horizons consists of a few metres thick crinoidal limestone containing the foraminifers Meandrospira favrei (Charollais, Brönnimann & Zaninetti), Sabaudia minuta Hofker and Montsalevia salevensis (Charollais, Brönnimann & Zaninetti) indicating a Late Valanginian-Early Hauterivian age. The biostratigraphical and sedimentological data obtained show that volcanism took place in several phases. Less intense phases of volcanism are recorded as thin tuffitic laminae within the upper parts of the Tithonian-early Mid Berriasian Sobótka Limestone Member and as fragments of volcanic rock in the carbonate breccia. The main phase(s) of volcanism took place during the Late Berriasian-?Early Valanginian

Peripheral circadian clocks are diversely affected by adrenalectomy

<p>Glucocorticoids are considered to synchronize the rhythmicity of clock genes in peripheral tissues; however, the role of circadian variations of endogenous glucocorticoids is not well defined. In the present study, we examined whether peripheral circadian clocks were impaired by adrenalectomy. To achieve this, we tested the circadian rhythmicity of core clock genes (<i>Bmal1, Per1-3, Cry1, RevErbα, Rora</i>), clock-output genes (<i>Dbp, E4bp4</i>) and a glucocorticoid- and clock-controlled gene (<i>Gilz</i>) in liver, jejunum, kidney cortex, splenocytes and visceral adipose tissue (VAT). Adrenalectomy did not affect the phase of clock gene rhythms but distinctly modulated clock gene mRNA levels, and this effect was partially tissue-dependent. Adrenalectomy had a significant inhibitory effect on the level of <i>Per1</i> mRNA in VAT, liver and jejunum, but not in kidney and splenocytes. Similarly, adrenalectomy down-regulated mRNA levels of <i>Per2</i> in splenocytes and VAT, <i>Per3</i> in jejunum, <i>RevErbα</i> in VAT and <i>Dbp</i> in VAT, kidney and splenocytes, whereas the mRNA amounts of <i>Per1</i> and <i>Per2</i> in kidney and <i>Per3</i> in VAT and splenocytes were up-regulated. On the other hand, adrenalectomy had minimal effects on <i>Rora</i> and <i>E4bp4</i> mRNAs. Adrenalectomy also resulted in decreased level of <i>Gilz</i> mRNA but did not alter the phase of its diurnal rhythm. Collectively, these findings suggest that adrenalectomy alters the mRNA levels of core clock genes and clock-output genes in peripheral organs and may cause tissue-specific modulations of their circadian profiles, which are reflected in changes of the amplitudes but not phases. Thus, the circulating corticosteroids are necessary for maintaining the high-amplitude rhythmicity of the peripheral clocks in a tissue-specific manner.</p

Historical Sketch of Slovak Haban (Hutterite) Population Based on Autosomal STR Analysis

According to the Hutterite chronicles, the Habans arrived from Austrian Tyrol, Switzerland, and northernmost Italy and stayed in four regions of Slovakia (Sobotište, Vel\u27ké Leváre, Moravský Svätý Ján, Trenčín). There are some communities in western Slovakia that retained their Haban cultural identity and still identify themselves as descendents of the Hutterite population with their own specific customs. Slovak Habans are typical founder population with significant social isolation for which high degree of inbreeding is typical. Present study investigated STR polymorphisms as a powerful genetic tool for population genetic studies. The aim was to perform a comparative, population genetic study based on 15 STR loci widely used in forensic genetics, of the Haban population, the Slovak majority population and the population of Tyrol. We analyzed allele frequencies and other statistical parameters in three selected populations in order to identify groups of specific ethnic origin and establish their genetic relationship. The data set included 110 unrelated Habans and 201 unrelated individuals from the Slovak majority population, as well as allelic frequencies for the population of Austrian Tyrol available in the literature. Population pairwise FST values used as a short term genetic distance between populations showed significant differentiation between the Habans and both reference populations (FST = 0.0025 and 0.0042 for comparison with the Slovaks and Austrians, respectively; p \u3c 10−3). The Slovak Hutterites were demonstrated to be genetically distinct and more closely related to their geographic neighbors than to their historical ancestral population, which may be at least partially explained by gene flow between neighboring Haban and Slovak populations