Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this issue of Cell Metabolism, Semenkovich and his colleagues show that ATM, a protein well known for its roles in the cellular response to DNA breaks, may also be linked to metabolic and cardiovascular diseases (Schneider et al., 2006). ATM seemingly does this by inhibiting JNK, a stress kinase involved in inflammation with related effects in insulin resistance and atherosclerosis. In an interesting twist, the authors show that chloroquine, an antimalarial drug, also activates ATM, which inhibits JNK, and improves insulin sensitivity and cardiovascular effects. These findings provide potential new insights into the pathogenesis and treatment of metabolic syndrome.
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PMID:Banking on ATM as a new target in metabolic syndrome. 1708 11

Metabolic syndrome is associated with insulin resistance and atherosclerosis. Here, we show that deficiency of one or two alleles of ATM, the protein mutated in the cancer-prone disease ataxia telangiectasia, worsens features of the metabolic syndrome, increases insulin resistance, and accelerates atherosclerosis in apoE-/- mice. Transplantation with ATM-/- as compared to ATM+/+ bone marrow increased vascular disease. Jun N-terminal kinase (JNK) activity was increased in ATM-deficient cells. Treatment of ATM+/+apoE-/- mice with low-dose chloroquine, an ATM activator, decreased atherosclerosis. In an ATM-dependent manner, chloroquine decreased macrophage JNK activity, decreased macrophage lipoprotein lipase activity (a proatherogenic consequence of JNK activation), decreased blood pressure, and improved glucose tolerance. Chloroquine also improved metabolic abnormalities in ob/ob and db/db mice. These results suggest that ATM-dependent stress pathways mediate susceptibility to the metabolic syndrome and that chloroquine or related agents promoting ATM activity could modulate insulin resistance and decrease vascular disease.
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PMID:ATM-dependent suppression of stress signaling reduces vascular disease in metabolic syndrome. 1708 7

Significant progress has been made in recent years elucidating the molecular controls of cellular responses to DNA damage in mammalian cells. Many of the insights that we have gained into the mechanisms involved in cellular DNA damage response pathways have come from studies of human cancer susceptibility syndromes that are altered in DNA damage responses. ATM, the gene mutated in the cancer-prone disorder, ataxia telangiectasia, is a protein kinase that is a central mediator of responses to DNA double strand breaks in cells. Such insights provide us with opportunities to develop new approaches to benefit patients. For example, inhibitors of the ATM pathway have the potential to act as sensitizers to chemotherapy or radiation therapy and could even have anti-neoplastic effects on their own. Conversely, activators of ATM could improve responses to cellular stresses such as oxidative damage. The potential benefits of ATM modulation in disease settings ranging from metabolic syndrome to cancer will be discussed.
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PMID:Our cells get stressed too! Implications for human disease. 1753 52

ATM is the most significant molecule involved in monitoring the genomic integrity of the cell. Any damage done to DNA relentlessly challenges the cellular machinery involved in recognition, processing and repair of these insults. ATM kinase is activated early to detect and signal lesions in DNA, arrest the cell cycle, establish DNA repair signaling and faithfully restore the damaged chromatin. ATM activation plays an important role as a barrier to tumorigenesis, metabolic syndrome and neurodegeneration. Therefore, studies of ATM-dependent DNA damage signaling pathways hold promise for treatment of a variety of debilitating diseases through the development of new therapeutics capable of modulating cellular responses to stress. In this review, we have tried to untangle the complex web of ATM signaling pathways with the purpose of pinpointing multiple roles of ATM underlying the complex phenotypes observed in AT patients.
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PMID:ATM protein kinase: the linchpin of cellular defenses to stress. 2153 82

ATM, mutation of which causes Ataxia telangiectasia, has emerged as a cardinal multifunctional protein kinase during past two decades as evidenced by various studies from around the globe. Further to its well established and predominant role in DNA damage response, ATM has also been understood to help in maintaining overall functional integrity of cells; since its mutation, inactivation or deficiency results in a variety of pathological manifestations besides DNA damage. These include oxidative stress, metabolic syndrome, mitochondrial dysfunction as well as neurodegeneration. Recently, high throughput screening using proteomics, metabolomics and transcriptomic studies revealed several proteins which might be acting as substrates of ATM. Studies that can help in identifying effective regulatory controls within the ATM-mediated pathways/mechanisms can help in developing better therapeutics. In fact, more in-depth understanding of ATM-dependent cellular signals could also help in the treatment of variety of other disease conditions since these pathways seem to control many critical cellular functions. In this review, we have attempted to put together a detailed yet lucid picture of the present-day understanding of ATM's role in various pathophysiological conditions involving DNA damage and beyond.
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PMID:ATM kinase: Much more than a DNA damage responsive protein. 2677 38

Metabolic syndrome and its pathological sequel, type 2 diabetes are considered as important global health problems. Metformin is the most common drug prescribed for patients with this disorder. Consequently, understanding the genetic pathways involved in pharmacokinetics and pharmacodynamics of this drug can have a considerable effect on the personalized treatment of type 2 diabetes. In this study, we evaluated the association between rs11212617 polymorphism of ATM gene and rs628031 of SLC22A1 gene with response to treatment in newly diagnosed type 2 diabetes patients. We genotyped rs11212617 and rs628031 polymorphism by PCR based restriction fragment length polymorphism (RFLP) and assessed the role of this polymorphisms on response to treatment in 140 patients who have been recently diagnosed with type 2 diabetes and were under monotherapy with metformin for 6 months. Response to metformin was defined by HbA1c and fasting blood sugar (FBS) values. Based on such evaluations, patients were divided into two groups: responders (n= 63) and non-responders (n= 77). No significant association was found between these polymorphisms and response to treatment (OR= 0.86, [95% CI 0.52-1.41], P= 0.32) for rs11212617 and (OR= 0.45, [95% CI 0.64-1.76], P= 0.45) for rs 628031. The reported gene variants in ATM and SLC22A1 are not significantly associated with metformin treatment response in type 2 diabetic patients in an Iranian population.
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PMID:Impact of ATM and SLC22A1 Polymorphisms on Therapeutic Response to Metformin in Iranian Diabetic Patients. 2738 33