13 research outputs found
ENPP1 Affects Insulin Action and Secretion: Evidences from In Vitro Studies
The aim of this study was to deeper investigate the mechanisms through which
ENPP1, a negative modulator of insulin receptor (IR) activation, plays a role on
insulin signaling, insulin secretion and eventually glucose metabolism. ENPP1
cDNA (carrying either K121 or Q121 variant) was transfected in HepG2 liver-, L6
skeletal muscle- and INS1E beta-cells. Insulin-induced IR-autophosphorylation
(HepG2, L6, INS1E), Akt-Ser473,
ERK1/2-Thr202/Tyr204 and GSK3-beta Ser9
phosphorylation (HepG2, L6), PEPCK mRNA levels (HepG2) and
2-deoxy-D-glucose uptake (L6) was studied. GLUT 4 mRNA
(L6), insulin secretion and caspase-3 activation (INS1E) were also investigated.
Insulin-induced IR-autophosphorylation was decreased in HepG2-K, L6-K, INS1E-K
(20%, 52% and 11% reduction vs. untransfected cells) and
twice as much in HepG2-Q, L6-Q, INS1E-Q (44%, 92% and 30%).
Similar data were obtained with Akt-Ser473,
ERK1/2-Thr202/Tyr204 and GSK3-beta Ser9 in
HepG2 and L6. Insulin-induced reduction of PEPCK mRNA was progressively lower in
untransfected, HepG2-K and HepG2-Q cells (65%, 54%, 23%).
Insulin-induced glucose uptake in untransfected L6 (60% increase over
basal), was totally abolished in L6-K and L6-Q cells. GLUT 4 mRNA was slightly
reduced in L6-K and twice as much in L6-Q (13% and 25% reduction
vs. untransfected cells). Glucose-induced insulin secretion was 60%
reduced in INS1E-K and almost abolished in INS1E-Q. Serum deficiency activated
caspase-3 by two, three and four folds in untransfected INS1E, INS1E-K and
INS1E-Q. Glyburide-induced insulin secretion was reduced by 50% in
isolated human islets from homozygous QQ donors as compared to those from KK and
KQ individuals. Our data clearly indicate that ENPP1, especially when the Q121
variant is operating, affects insulin signaling and glucose metabolism in
skeletal muscle- and liver-cells and both function and survival of insulin
secreting beta-cells, thus representing a strong pathogenic factor predisposing
to insulin resistance, defective insulin secretion and glucose metabolism
abnormalities
The Gene Ontology resource: enriching a GOld mine
The Gene Ontology Consortium (GOC) provides the most comprehensive resource currently available for computable knowledge regarding the functions of genes and gene products. Here, we report the advances of the consortium over the past two years. The new GO-CAM annotation framework was notably improved, and we formalized the model with a computational schema to check and validate the rapidly increasing repository of 2838 GO-CAMs. In addition, we describe the impacts of several collaborations to refine GO and report a 10% increase in the number of GO annotations, a 25% increase in annotated gene products, and over 9,400 new scientific articles annotated. As the project matures, we continue our efforts to review older annotations in light of newer findings, and, to maintain consistency with other ontologies. As a result, 20 000 annotations derived from experimental data were reviewed, corresponding to 2.5% of experimental GO annotations. The website (http://geneontology.org) was redesigned for quick access to documentation, downloads and tools. To maintain an accurate resource and support traceability and reproducibility, we have made available a historical archive covering the past 15 years of GO data with a consistent format and file structure for both the ontology and annotations
Global urban environmental change drives adaptation in white clover.
Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale