Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity and type 2 diabetes constitute leading public health problems worldwide. Studies have shown that insulin resistance affiliated with these conditions is associated with skeletal muscle lipid accumulation, while the latter is associated with mitochondrial dysfunctions. However, the initiation and regulation of mitochondrial biogenesis rely heavily on approximately 1000 nuclear-encoded mitochondrial regulatory proteins. In this study, we targeted the ubiquinol-cytochrome c reductase core protein I gene, a nuclear-encoded component of mitochondrial complex III, for its association with subcutaneous fat depth (SFD) and skeletal muscle lipid accumulation (SMLA) using cattle as a model. Four promoter polymorphisms were identified and genotyped on approximately 250 Wagyu x Limousin F2 progeny. Statistical analysis revealed that two completely linked polymorphic sites, g.13487C>T and g.13709G>C (r2 = 1), were significantly associated with both SFD (p < 0.01) and SMLA (p < 0.0001). The difference between TTCC and CCGG haplotypes was 0.178 cm for SFD and 0.624 scores for SMLA. Interestingly, the former haplotype produced higher promoter activities than the latter by 43% to 49% in three cell lines (p < 0.05). In addition to Rett syndrome and breast/ovarian cancer observed in other studies, we report evidence for the first time, to our knowledge, that overexpression of ubiquinol-cytochrome c reductase core protein I might affect mitochondrial morphology and/or physiology and lead to development of obesity and related conditions.
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PMID:Functional UQCRC1 polymorphisms affect promoter activity and body lipid accumulation. 1819 95

Neurotrophins, particularly, NGF and BDNF are now well recognized to mediate a dizzying number of trophobiological effects, ranging from the Rita Levi-Montalcini's neurotrophic through immunotrophic to metabotrophic effects.These are implicated in the pathogenesis of various diseases including neuropsychiatric and cardiometabolic diseases, such as dementia, depression, type 2 diabetes and obesity that may express a common phenotype and coexistence. Recently, adipobiology (adiposcience) as become a focus of numerous studies showing that the adipose tissue is the body's largest endocrine organ producing multiple signaling proteins, including NGF and BDNF, all these dubbed adipokines. On the basis of our and other authors' evidence that low NGF and/or BDNF levels are found in cardiometabolic diseases (atherosclerosis, obesity, type 2 diabetes, metabolic syndrome), a hypothesis of a critical role of neuro-metabotrophic deficit in the pathogenesis of these diseases has been raised. Since NGF and BDNF also exerts various synaptotrophic effects involved in cognitive enhancement, this hypothesis might also be related to neuropsychiatric diseases such as dementia, depression, schizophrenia, autism, Rett syndrome, anorexia nervosa, and bulimia nervosa. Finally, NGF- and BDNF-based therapeutic approach, including ampakines, antidepressants, selective deacetylase inhibitors, statins, peroxisome proliferator-activated receptor gamma agonists, and "brain food" and calorie restriction, is outlined.
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PMID:NGF and BDNF: from nerves to adipose tissue, from neurokines to metabokines. 2006 8

The orchestrated organization of epigenetic factors that control chromatin dynamism, including DNA methylation, histone marks, non-coding RNAs (ncRNAs) and chromatin-remodeling proteins, is essential for the proper function of tissue homeostasis, cell identity and development. Indeed, deregulation of epigenetic profiles has been described in several human pathologies, including complex diseases (such as cancer, cardiovascular and neurological diseases), metabolic pathologies (type 2 diabetes and obesity) and imprinting disorders. Over the last decade it has become increasingly clear that mutations of genes involved in epigenetic mechanism, such as DNA methyltransferases, methyl-binding domain proteins, histone deacetylases, histone methylases and members of the SWI/SNF family of chromatin remodelers are linked to human disorders, including Immunodeficiency Centromeric instability Facial syndrome 1, Rett syndrome, Rubinstein-Taybi syndrome, Sotos syndrome or alpha-thalassemia/mental retardation X-linked syndrome, among others. As new members of the epigenetic machinery are described, the number of human syndromes associated with epigenetic alterations increases. As recent examples, mutations of histone demethylases and members of the non-coding RNA machinery have recently been associated with Kabuki syndrome, Claes-Jensen X-linked mental retardation syndrome and Goiter syndrome. In this review, we describe the variety of germline mutations of epigenetic modifiers that are known to be associated with human disorders, and discuss the therapeutic potential of epigenetic drugs as palliative care strategies in the treatment of such disorders.
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PMID:Genetic syndromes caused by mutations in epigenetic genes. 2337 May 4

Epigenetics refers to a variety of processes that have heritable effects on gene expression programs without changes in DNA sequence. Key players in epigenetic control are chemical modifications to DNA, histone, and non-histone chromosomal proteins, which establish a complex regulatory network that controls genome function. Methylation of DNA at the fifth position of cytosine in CpG dinucleotides (5-methylcytosine, 5mC), which is carried out by DNA methyltransferases, is commonly associated with gene silencing. However, high resolution mapping of DNA methylation has revealed that 5mC is enriched in exonic nucleosomes and at intron-exon junctions, suggesting a role of DNA methylation in the relationship between elongation and RNA splicing. Recent studies have increased our knowledge of another modification of DNA, 5-hydroxymethylcytosine (5hmC), which is a product of the ten-eleven translocation (TET) proteins converting 5mC to 5hmC. In this review, we will highlight current studies on the role of 5mC and 5hmC in regulating gene expression (using some aspects of brain development as examples). Further the roles of these modifications in detection of pathological states (type 2 diabetes, Rett syndrome, fetal alcohol spectrum disorders and teratogen exposure) will be discussed.
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PMID:DNA modifications: function and applications in normal and disease States. 2534 Jun 99