Resistin-Like Molecule-β Inhibits SGLT-1 Activity and Enhances GLUT2-Dependent Jejunal Glucose Transport

International audienceOBJECTIVE: An increased expression of RELM-beta (resistin-like molecule-beta), a gut-derived hormone, is observed in animal models of insulin resistance/obesity and intestinal inflammation. Intestinal sugar absorption is modulated by dietary environment and hormones/cytokines. The aim of this study was to investigate the effect of RELM-beta on intestinal glucose absorption. RESEARCH DESIGN AND METHODS: Oral glucose tolerance test was performed in mice and rats in the presence and the absence of RELM-beta. The RELM-beta action on glucose transport in rat jejunal sacs, everted rings, and mucosal strips was explored as well as downstream kinases modulating SGLT-1 and GLUT2 glucose transporters. RESULTS: Oral glucose tolerance test carried out in rodents showed that oral administration of RELM-beta increased glycemia. Studies in rat jejunal tissue indicated that mucosal RELM-beta promoted absorption of glucose from the gut lumen. RELM-beta had no effect on paracellular mannitol transport, suggesting a transporter-mediated transcellular mechanism. In studies with jejunal mucosa mounted in Ussing chamber, luminal RELM-beta inhibited SGLT-1 activity in line with a diminished SGLT-1 abundance in brush border membranes (BBMs). Further, the potentiating effect of RELM-beta on jejunal glucose uptake was associated with an increased abundance of GLUT2 at BBMs. The effects of RELM-beta were associated with an increased amount of protein kinase C betaII in BBMs and an increased phosphorylation of AMP-activated protein kinase (AMPK). CONCLUSIONS: The regulation of SGLT-1 and GLUT2 by RELM-beta expands the role of gut hormones in short-term AMPK/protein kinase C mediated control of energy balance

Family composition and age at menarche: findings from the international Health Behaviour in School-Aged Children Study

This research was funded by The University of St Andrews and NHS Health Scotland.Background Early menarche has been associated with father absence, stepfather presence and adverse health consequences in later life. This article assesses the association of different family compositions with the age at menarche. Pathways are explored which may explain any association between family characteristics and pubertal timing. Methods Cross-sectional, international data on the age at menarche, family structure and covariates (age, psychosomatic complaints, media consumption, physical activity) were collected from the 2009–2010 Health Behaviour in School-aged Children (HBSC) survey. The sample focuses on 15-year old girls comprising 36,175 individuals across 40 countries in Europe and North America (N = 21,075 for age at menarche). The study examined the association of different family characteristics with age at menarche. Regression and path analyses were applied incorporating multilevel techniques to adjust for the nested nature of data within countries. Results Living with mother (Cohen’s d = .12), father (d = .08), brothers (d = .04) and sisters (d = .06) are independently associated with later age at menarche. Living in a foster home (d = −.16), with ‘someone else’ (d = −.11), stepmother (d = −.10) or stepfather (d = −.06) was associated with earlier menarche. Path models show that up to 89% of these effects can be explained through lifestyle and psychological variables. Conclusions Earlier menarche is reported amongst those with living conditions other than a family consisting of two biological parents. This can partly be explained by girls’ higher Body Mass Index in these families which is a biological determinant of early menarche. Lower physical activity and elevated psychosomatic complaints were also more often found in girls in these family environments.Publisher PDFPeer reviewe

Phylogeny, Diet, and Cranial Integration in Australodelphian Marsupials

Studies of morphological integration provide valuable information on the correlated evolution of traits and its relationship to long-term patterns of morphological evolution. Thus far, studies of morphological integration in mammals have focused on placentals and have demonstrated that similarity in integration is broadly correlated with phylogenetic distance and dietary similarity. Detailed studies have also demonstrated a significant correlation between developmental relationships among structures and adult morphological integration. However, these studies have not yet been applied to marsupial taxa, which differ greatly from placentals in reproductive strategy and cranial development and could provide the diversity necessary to assess the relationships among phylogeny, ecology, development, and cranial integration. This study presents analyses of morphological integration in 20 species of australodelphian marsupials, and shows that phylogeny is significantly correlated with similarity of morphological integration in most clades. Size-related correlations have a significant affect on results, particularly in Peramelia, which shows a striking decrease in similarity of integration among species when size is removed. Diet is not significantly correlated with similarity of integration in any marsupial clade. These results show that marsupials differ markedly from placental mammals in the relationships of cranial integration, phylogeny, and diet, which may be related to the accelerated development of the masticatory apparatus in marsupials

Association of Variants in RETN With Plasma Resistin Levels and Diabetes-Related Traits in the Framingham Offspring Study

OBJECTIVE— The RETN gene encodes the adipokine resistin. Associations of RETN with plasma resistin levels, type 2 diabetes, and related metabolic traits have been inconsistent. Using comprehensive linkage disequilibrium mapping, we genotyped tag single nucleotide polymorphisms (SNPs) in RETN and tested associations with plasma resistin levels, risk of diabetes, and glycemic traits

Novel Arenavirus Sequences in Hylomyscus sp. and Mus (Nannomys) setulosus from Côte d'Ivoire: Implications for Evolution of Arenaviruses in Africa

This study aimed to identify new arenaviruses and gather insights in the evolution of arenaviruses in Africa. During 2003 through 2005, 1,228 small mammals representing 14 different genera were trapped in 9 villages in south, east, and middle west of Côte d'Ivoire. Specimens were screened by pan-Old World arenavirus RT-PCRs targeting S and L RNA segments as well as immunofluorescence assay. Sequences of two novel tentative species of the family Arenaviridae, Menekre and Gbagroube virus, were detected in Hylomyscus sp. and Mus (Nannomys) setulosus, respectively. Arenavirus infection of Mus (Nannomys) setulosus was also demonstrated by serological testing. Lassa virus was not found, although 60% of the captured animals were Mastomys natalensis. Complete S RNA and partial L RNA sequences of the novel viruses were recovered from the rodent specimens and subjected to phylogenetic analysis. Gbagroube virus is a closely related sister taxon of Lassa virus, while Menekre virus clusters with the Ippy/Mobala/Mopeia virus complex. Reconstruction of possible virus–host co-phylogeny scenarios suggests that, within the African continent, signatures of co-evolution might have been obliterated by multiple host-switching events

Cryptic speciation and chromosomal repatterning in the South African climbing mice Dendromus (Rodentia, Nesomyidae)

We evaluate the intra- and interspecific diversity in the four South African rodent species of the genus Dendromus. The molecular phylogenetic analysis on twenty-three individuals have been conducted on a combined dataset of nuclear and mitochondrial markers. Moreover, the extent and processes underlying chromosomal variation, have been investigated on three species by mean of G-, C-bands, NORs and Zoo-FISH analysis. The molecular analysis shows the presence of six monophyletic lineages corresponding to D. mesomelas, D. mystacalis and four lineages within D. cfr. melanotis with high divergence values (ranges: 10.6% – 18.3%) that raises the question of the possible presence of cryptic species. The first description of the karyotype for D. mesomelas and D. mystacalis and C- and G- banding for one lineage of D. cfr. melanotis are reported highlighting an extended karyotype reorganization in the genus. Furthermore, the G-banding and Zoo-FISH evidenced an autosome-sex chromosome translocation characterizing all the species and our timing estimates this mutation date back 7.4 mya (Late Miocene). Finally, the molecular clock suggests that cladogenesis took place since the end of Miocene to Plio-Pleistocene, probably due to ecological factors, isolation in refugia followed by differential adaptation to the mesic or dry habitat

An Inflammatory Cascade Leading to Hyperresistinemia in Humans

BACKGROUND: Obesity, the most common cause of insulin resistance, is increasingly recognized as a low-grade inflammatory state. Adipocyte-derived resistin is a circulating protein implicated in insulin resistance in rodents, but the role of human resistin is uncertain because it is produced largely by macrophages. METHODS AND FINDINGS: The effect of endotoxin and cytokines on resistin gene and protein expression was studied in human primary blood monocytes differentiated into macrophages and in healthy human participants. Inflammatory endotoxin induced resistin in primary human macrophages via a cascade involving the secretion of inflammatory cytokines that circulate at increased levels in individuals with obesity. Induction of resistin was attenuated by drugs with dual insulin-sensitizing and anti-inflammatory properties that converge on NF-κB. In human study participants, experimental endotoxemia, which produces an insulin-resistant state, causes a dramatic rise in circulating resistin levels. Moreover, in patients with type 2 diabetes, serum resistin levels are correlated with levels of soluble tumor necrosis factor α receptor, an inflammatory marker linked to obesity, insulin resistance, and atherosclerosis. CONCLUSIONS: Inflammation is a hyperresistinemic state in humans, and cytokine induction of resistin may contribute to insulin resistance in endotoxemia, obesity, and other inflammatory states