Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Interactions between genetic background, insulin resistance and ?-cell function.

ABSTRACT: An interaction between genes and the environment is a critical component underlying the pathogenesis of the hyperglycaemia of type 2 diabetes. The development of more sophisticated techniques for studying gene variants and for analysing genetic data has led to the discovery of some 40 genes associated with type 2 diabetes. Most of these genes are related to changes in ?-cell function, with a few associated with decreased insulin sensitivity and obesity. Interestingly, using quantitative traits based on continuous measures rather than dichotomous ones, it has become evident that not all genes associated with changes in fasting or post-prandial glucose are also associated with a diagnosis of type 2 diabetes. Identification of these gene variants has provided novel insights into the physiology and pathophysiology of the ?-cell, including the identification of molecules involved in ?-cell function that were not previously recognized as playing a role in this critical cell.

SUBMITTER: Kahn SE

PROVIDER: S-EPMC3634618 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Interactions between genetic background, insulin resistance and β-cell function.

Kahn S E SE Suvag S S Wright L A LA Utzschneider K M KM

Diabetes, obesity & metabolism 20121001

An interaction between genes and the environment is a critical component underlying the pathogenesis of the hyperglycaemia of type 2 diabetes. The development of more sophisticated techniques for studying gene variants and for analysing genetic data has led to the discovery of some 40 genes associated with type 2 diabetes. Most of these genes are related to changes in β-cell function, with a few associated with decreased insulin sensitivity and obesity. Interestingly, using quantitative traits b ...[more]

PMID: 22928564

Similar Datasets

Virulence phenotypes result from interactions between pathogen ploidy and genetic background.

Project description:Studying fungal virulence is often challenging and frequently depends on many contexts, including host immune status and pathogen genetic background. However, the role of ploidy has often been overlooked when studying virulence in eukaryotic pathogens. Since fungal pathogens, including the human opportunistic pathogen Candida albicans, can display extensive ploidy variation, assessing how ploidy impacts virulence has important clinical relevance. As an opportunistic pathogen, C. albicans causes nonlethal, superficial infections in healthy individuals, but life-threatening bloodstream infections in individuals with compromised immune function. Here, we determined how both ploidy and genetic background of C. albicans impacts virulence phenotypes in healthy and immunocompromised nematode hosts by characterizing virulence phenotypes in four near-isogenic diploid and tetraploid pairs of strains, which included both laboratory and clinical genetic backgrounds. We found that C. albicans infections decreased host survival and negatively impacted host reproduction, and we leveraged these two measures to survey both lethal and nonlethal virulence phenotypes across the multiple C. albicans strains. In this study, we found that regardless of pathogen ploidy or genetic background, immunocompromised hosts were susceptible to fungal infection compared to healthy hosts. Furthermore, for each host context, we found a significant interaction between C. albicans genetic background and ploidy on virulence phenotypes, but no global differences between diploid and tetraploid pathogens were observed.

| S-EPMC7487253 | biostudies-literature

Interplay between genetic background and genome evolution

Project description:We used genome-wide microarray comparative genomic hybridization to investigate the response of cells of related genetic backgrounds to challenge with methotrexate to gain a better understanding of the underlying defects which foster specific aberrations. Keywords: array CGH

2007-12-01 | GSE8695 | GEO

Interactions between innate immunity and insulin signaling affect resistance to infection in insects.

Project description:An active immune response is energetically demanding and requires reallocation of nutrients to support resistance to and tolerance of infection. Insulin signaling is a critical global regulator of metabolism and whole-body homeostasis in response to nutrient availability and energetic needs, including those required for mobilization of energy in support of the immune system. In this review, we share findings that demonstrate interactions between innate immune activity and insulin signaling primarily in the insect model Drosophila melanogaster as well as other insects like Bombyx mori and Anopheles mosquitos. These studies indicate that insulin signaling and innate immune activation have reciprocal effects on each other, but that those effects vary depending on the type of pathogen, route of infection, and nutritional status of the host. Future research will be required to further understand the detailed mechanisms by which innate immunity and insulin signaling activity impact each other.

| S-EPMC10616485 | biostudies-literature

Role of the Genetic Background in Resistance to Plant Viruses.

Project description:In view of major economic problems caused by viruses, the development of genetically resistant crops is critical for breeders but remains limited by the evolution of resistance-breaking virus mutants. During the plant breeding process, the introgression of traits from Crop Wild Relatives results in a dramatic change of the genetic background that can alter the resistance efficiency or durability. Here, we conducted a meta-analysis on 19 Quantitative Trait Locus (QTL) studies of resistance to viruses in plants. Frequent epistatic effects between resistance genes indicate that a large part of the resistance phenotype, conferred by a given QTL, depends on the genetic background. We next reviewed the different resistance mechanisms in plants to survey at which stage the genetic background could impact resistance or durability. We propose that the genetic background may impair effector-triggered dominant resistances at several stages by tinkering the NB-LRR (Nucleotide Binding-Leucine-Rich Repeats) response pathway. In contrast, effects on recessive resistances by loss-of-susceptibility-such as eIF4E-based resistances-are more likely to rely on gene redundancy among the multigene family of host susceptibility factors. Finally, we show how the genetic background is likely to shape the evolution of resistance-breaking isolates and propose how to take this into account in order to breed plants with increased resistance durability to viruses.

| S-EPMC6213453 | biostudies-other

Interactions between the Bumblebee Bombus pascuorum and Red Clover (Trifolium pratense) Are Mediated by Plant Genetic Background.

Project description:Wildflower mixes are often planted around field margins to provide forage for pollinators. Although seed for these mixtures is often wild-sourced, for species where agricultural cultivars are available, for example red clover (Trifolium pratense), cultivars can also be included. Previous evidence suggests that plant genetic background can have a strong influence on plant-arthropod interactions and therefore the provenance and genetic background of the plants included in wildflower mixes could impact plant-pollinator interactions. We tested the performance of five individual T. pratense cultivars against two commercially available wild-sourced T. pratense populations in terms of their ability to attract potential pollinator species (focusing on bumblebees) and their floral traits using greenhouse and garden experiments. The main bumblebee observed interacting with T. pratense was Bombus pascuorum and we found no difference in the absolute number of B. pascuorum visiting the cultivars or wild populations. However, we found variation among cultivars and between wild populations in their ability to attract bumblebees, which seems to be related to their relative investment in different floral traits. There was a positive relationship between biomass and number of inflorescences produced by the wild populations of T. pratense, which was not apparent for the cultivars. This suggests that artificial selection on the cultivars has changed the G-matrix of correlated traits. We show that agricultural cultivars of T. pratense can be as effective as wild populations at attracting pollinators such as bumblebees, but that the genetic background of both cultivars and wild populations can have a significant impact on the attractiveness of the plant to pollinators. We also show divergence in the correlated traits of T. pratense cultivars and wild populations that could lead to outbreeding depression if the plants interbreed.

| S-EPMC4995044 | biostudies-literature

Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations.

Project description:ObjectiveParoxysmal epileptiform abnormalities on electroencephalography (EEG) are the hallmark of epilepsies, but it is uncertain to what extent epilepsy and background EEG oscillations share neurobiological underpinnings. Here, we aimed to assess the genetic correlation between epilepsy and background EEG oscillations.MethodsConfounding factors, including the heterogeneous etiology of epilepsies and medication effects, hamper studies on background brain activity in people with epilepsy. To overcome this limitation, we compared genetic data from a genome-wide association study (GWAS) on epilepsy (n = 12 803 people with epilepsy and 24 218 controls) with that from a GWAS on background EEG (n = 8425 subjects without epilepsy), in which background EEG oscillation power was quantified in four different frequency bands: alpha, beta, delta, and theta. We replicated our findings in an independent epilepsy replication dataset (n = 4851 people with epilepsy and 20 428 controls). To assess the genetic overlap between these phenotypes, we performed genetic correlation analyses using linkage disequilibrium score regression, polygenic risk scores, and Mendelian randomization analyses.ResultsOur analyses show strong genetic correlations of genetic generalized epilepsy (GGE) with background EEG oscillations, primarily in the beta frequency band. Furthermore, we show that subjects with higher beta and theta polygenic risk scores have a significantly higher risk of having generalized epilepsy. Mendelian randomization analyses suggest a causal effect of GGE genetic liability on beta oscillations.SignificanceOur results point to shared biological mechanisms underlying background EEG oscillations and the susceptibility for GGE, opening avenues to investigate the clinical utility of background EEG oscillations in the diagnostic workup of epilepsy.

| S-EPMC8672363 | biostudies-literature

Interactions between insulin resistance, epigenetics, and donor sex in control of gene expression in human iPS cell-derived myoblasts

Project description:About 25% of people within the general population are insulin resistant, increasing the risk for type 2 diabetes (T2D) and metabolic disease. Transcriptomic analysis of iPS cells differentiated into myoblasts (iMyos) from insulin resistant (I-Res) versus insulin sensitive (I-Sen) non-diabetic individuals reveals 306 genes increased and 271 genes decreased in expression in iMyos from insulin resistant donors with differences of 2-folds or more. Over 30 of the genes changed in I-Res iMyos are associated with T2D by SNP polymorphisms and functionally linked to insulin action and control of metabolism. Interestingly, we also identified >1500 differences in gene expression that were dependent on sex of the cell donor, some of which modified the insulin resistance effects. Many of these sex-differences were associated with increased DNA methylation in cells from females and reversed by 5-azacytidine. By contrast, the insulin sensitivity differences were not reversed and thus appear to reflect genetic or methylation-independent epigenetic effects.

2024-01-17 | GSE244307 | GEO

Strong interactions between solitons and background light in Brillouin-Kerr microcombs

Project description: Not available

| S-EPMC10891115 | biostudies-literature

Polyunsaturated Fatty Acids Modulate the Association between PIK3CA-KCNMB3 Genetic Variants and Insulin Resistance.

Project description:BackgroundNeighboring genes PIK3CA and KCNMB3 are both important for insulin signaling and ?-cell function, but their associations with glucose-related traits are unclear.ObjectiveThe objective was to examine associations of PIK3CA-KCNMB3 variants with glucose-related traits and potential interaction with dietary fat.DesignWe first investigated genetic associations and their modulation by dietary fat in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study (n?=?820). Nine single-nucleotide polymorphisms (SNPs) were selected for analysis, covering more than 80% of the SNPs in the region. We then sought to replicate the findings in the Boston Puerto Rican Health Study (BPRHS) (n?=?844).ResultsFor KCNMB3 missense mutation rs7645550, meta-analysis indicated that homeostasis model assessment of insulin resistance (HOMA-IR) was significantly lower in minor allele T homozygotes compared with major allele C carriers (pooled P-value?=?0.004); for another SNP rs1183319, which is in moderate LD with rs7645550, minor allele G carriers had higher HOMA-IR compared with non-carriers in both populations (pooled P-value?=?0.028). In GOLDN, rs7645550 T allele homozygotes had lower HOMA-IR only when dietary n-3: n-6 PUFA ratio was low (?0.11, P?=?0.001), but not when it was high (>0.11, P-interaction?=?0.033). Similar interaction was observed between rs1183319 and n-3: n-6 PUFA ratio on HOMA-IR (P-interaction?=?0.001) in GOLDN. Variance contribution analyses in GOLDN confirmed the genetic association and gene-diet interaction. In BPRHS, dietary n-3: n-6 PUFA ratio significantly modulated the association between rs1183319 and HbA1c (P-interaction?=?0.034).ConclusionPIK3CA-KCNMB3 variants are associated with insulin resistance in populations of different ancestries, and are modified by dietary PUFA.

| S-EPMC3694924 | biostudies-literature

Genetic regulator of mitochondrial metabolism and insulin resistance

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-09-24 | GSE162021 | GEO