Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alterations of the intrauterine and early postnatal nutritional, metabolic, and hormonal environment may cause predispositions to the development of disorders and diseases in later life. Mechanisms responsible for this perinatally acquired 'malprogramming' still remain unclear. It has long been known, however, that hormones are environment-dependent organizers of the developing 'neuroendocrine-immune network', which regulates all fundamental processes of life. When present in nonphysiological concentrations during critical ontogenetic periods, hormones can therefore also act as 'endogenous functional teratogens'. Fetal and neonatal hyperinsulinism is a pathognomic feature in the offspring of diabetic mothers. Perinatal hyperinsulinism also occurs due to early postnatal overfeeding. Data obtained by our group indicate that elevated insulin concentrations during critical periods of perinatal life may induce a lasting 'malprogramming' of neuroendocrine systems regulating body weight, food intake, and metabolism. Similar characteristics may occur due to perinatal hyperleptinism, hypercortisolism etc. Since mechanisms of early 'programming' of obesity, diabetes, and the metabolic syndrome X are unclear, a complex 'neuroendocrine malprogramming' of the regulation of body weight and metabolism may provide a general etiopathogenetic concept in this context, exemplarily revealing critical new implications for chances and challenges of perinatal preventive medicine in the future.
 ...
PMID:'Fetal programming' and 'functional teratogenesis': on epigenetic mechanisms and prevention of perinatally acquired lasting health risks. 1534 12

Differences on measures of metabolic syndrome X and coronary heart disease (CHD) risk, as well as potential pathophysiological mediators, inflammation, and oxidative stress, were examined as a function of HIV serostatus and highly active antiretroviral therapy (HAART) regimen with and without protease inhibitors (PIs). Data from 164 men and women, aged 18 to 55 yr, were used to compare 82 HIV+ subjects who were free of hepatitis C virus and were on a stable HAART regimen for >/=6 mo, with 82 seronegative subjects matched on age, sex, body mass index, and ethnicity. For the HIV+ subjects, after controlling for diabetes status and HIV disease progression, PI exposure was associated with greater oxidative stress, triglyceridemia, and lipidemia than it was for non-PI-exposed HIV+ subjects, and the risk of a future myocardial infarction was up to 56% greater in PI-exposed than in non-PI-exposed subjects and 129% greater than in controls. Although it is likely that the greatest proportion of CHD risk in the HIV+ subjects may be accounted for by pathological conditions linked to HIV infection in interaction with mediating processes such as inflammation, central obesity, and dyslipidemia, which was greater than in controls, it appears that PI medications may exacerbate oxidative stress and hypertriglyceridemia to enhance this risk.
 ...
PMID:HIV, metabolic syndrome X, inflammation, oxidative stress, and coronary heart disease risk : role of protease inhibitor exposure. 1547 Feb 77

Comparative physiology traditionally relies on unusual animals to explore the mechanistic basis or evolution of physiological processes. Despite his credentials as a comparative physiologist, much of the recent work by Peter Hochachka relied upon humans as "comparative" models. Technological advances in clinical analyses and expanding databases of genomic diversity have made humans a very "convenient" model to study the evolution of metabolism. For example, a growing number of metabolic diseases have been shown to have a genetic basis. Obesity, type II diabetes, metabolic syndrome X may each have linkages to polymorphisms in genes encoding transcriptional regulators of bioenergetic genes. Genetic polymorphisms and gene families for these important transcription factors inspire questions about the evolution of energy metabolism in other animals. Thus, these biomedical studies provide important direction for researchers interested in exploring the regulatory basis of interspecies variations in bioenergetics.
 ...
PMID:Using humans to study the physiological evolution of energy metabolism: a tribute to Peter Hochachka. 1554 70

Metabolic syndrome X and type 2 diabetes share many metabolic and morphological similarities with Cushing's syndrome, a rare disorder caused by systemic glucocorticoid excess. Pathologies frequently associated with these diseases include insulin resistance, atherosclerosis, susceptibility to infection, poor wound healing, and hypertension. The similarity of the clinical profiles associated with these disorders suggests the influence of a common molecular mechanism for disease onset. Interestingly, numerous studies identify ceramides and other sphingolipids as potential contributors to these sequelae. Herein we review studies demonstrating that aberrant ceramide accumulation contributes to the development of the deleterious clinical manifestations associated with these diseases.
Diabetes 2005 Mar
PMID:A role for sphingolipids in producing the common features of type 2 diabetes, metabolic syndrome X, and Cushing's syndrome. 1573 32

Pyruvic acid, an intermediate metabolite of glucose, an effective scavenger of reactive oxygen species (ROS), inhibits tumor necrosis factor-alpha production and NF-kappaB signaling pathways, reduces circulating levels of HMGB1 (high mobility group B1), decreases COX-2 (cyclo-oxygenase-2), iNOS (inducible nitric oxide synthase), and IL-6 (interleukin-6) mRNA expression in liver, ileal mucosa, and colonic mucosa in animal models with endotoxemia. These studies suggest that pyruvate has potent anti-oxidant and anti-inflammatory actions. Insulin influences the production of pyruvate by its action on glucose metabolism and pyruvate is an insulin secretagogue. This suggests that in metabolic syndrome X, obesity, hypertension, diabetes mellitus, and cancer (where insulin resistance is common due to enhanced TNF-alpha production) pyruvate plays a role. This may have relevance to the use of glucose-insulin-potassium regimen in these clinical conditions, sepsis, and cancer.
 ...
PMID:Pyruvate is an endogenous anti-inflammatory and anti-oxidant molecule. 1664 87

The association of elevated serum uric acid (hyperuricemia, gout) with the presence of classical coronary risk factors and coronary artery disease (CAD) or myocardial infarction (MI) has been analysed in many epidemiological studies. Numerous studies have revealed that hypertension, high body mass index (BMI), lipid disorders (especially raised triglycerides--TG level and low high dense lipoprotein cholesterol HDL-C level), increased creatinine or insulin levels have caused hyperuricemia. No association has been observed between hyperuricemia and diabetes type 2 and uricemia and glicemia. But in some studies the relationship between cholesterol and uric acid levels has been not confirmed. Hyperuricemia has been observed in patients with non-treated hypertension. Gout has often occurred with typical disorders for the metabolic syndrome X. Significant correlation of the serum uric level and the CAD presence and severity of coronary atherosclerosis confirmed by coronary angiography has been observed in women. Hyperuricemia has also indirect influence on progress of CAD by physical activity restriction, what causes sedentary mode of life and lead to obesity. Obesity is a known risk factor diabetes, lipid disorders and hypertension. To recapitulate, it is a matter of controversy as to whether uric acid is an independent cardiovascular risk factor or rather it only represents reinforcement of typical risk factor.
 ...
PMID:[Is hyperuricemia a cardiovascular risk factor?]. 1701 83

Plasma levels of C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and lipid peroxides are high whereas those of endothelial nitric oxide are low in insulin resistance, obesity, type 2 diabetes mellitus, hypertension, hyperlipidemias, metabolic syndrome X, and Alzheimer's disease suggesting that these diseases are characterized by low-grade systemic inflammation. Recent studies showed that the plasma and tissue activities of enzymes butyrylcholinesterase and acetylcholinesterase are elevated in patients with Alzheimer's disease, and diabetes mellitus, hypertension, insulin resistance, and hyperlipidemia. As a result of this increase in the activities of enzymes acetylcholinesterase and butyrylcholinesterase, the plasma and tissue levels of acetylcholine (ACh) will be low. The "cholinergic anti-inflammatory pathway" mediated by acetylcholine acts by inhibiting the production of tumor necrosis factor, interleukin-1, macrophage migration inhibitory factor, and high mobility group box-1 and suppresses the activation of nuclear factor-kappa B expression. ACh is a neurotransmitter and regulates the levels and activities of serotonin, dopamine and other neuropeptides and thus, modulates both immune response and neurotransmission. Hence, both acetylcholinesterase and butyrylcholinesterase by inactivating acetylcholine may enhance inflammation. This suggests that increased plasma and tissue activities of acetylcholinesterase and butyrylcholinesterase seen in various clinical conditions could serve as a marker of low-grade systemic inflammation.
 ...
PMID:Acetylcholinesterase and butyrylcholinesterase as possible markers of low-grade systemic inflammation. 1804 45

Obesity is an important component of metabolic syndrome X and predisposes to the development of type 2 diabetes mellitus. The incidence of obesity, type 2 diabetes mellitus and metabolic syndrome X is increasing, and the cause(s) for this increasing incidence is not clear. Although genetics could play an important role in the higher prevalence of these diseases, it is not clear how genetic factors interact with environmental and dietary factors to increase their incidence. We performed gene expression profile in subjects with obesity and type 2 diabetes mellitus with and without family history of these diseases. It was noted that genes involved in carbohydrate, lipid and amino acid metabolism pathways, glycan of biosynthesis, metabolism of cofactors and vitamin pathways, ubiquitin mediated proteolysis, signal transduction pathways, neuroactive ligand-receptor interaction, nervous system pathways, neurodegenerative disorders pathways are upregulated in obesity compared to healthy subjects. In contrast genes involved in cell adhesion molecules, cytokine-cytokine receptor interaction, insulin signaling and immune system pathways are downregulated in obese. Genes involved in signal transduction, regulation of actin cytoskeleton, antigen processing and presentation, complement and coagulation cascades, axon guidance and neurodegenerative disorders pathways are upregulated in subjects with type 2 diabetes with family history of diabetes compared to those who are diabetic but with no family history. Genes involved in oxidative phosphorylation, immune, nervous system, and metabolic disorders pathways are upregulated in those with diabetes with family history of diabetes compared to those with diabetes but with no family history. In contrast, genes involved in lipid and amino acid pathways, ubiquitin mediated proteolysis, signal transduction, insulin signaling and PPAR signaling pathways are downregulated in subjects with diabetes with family history of diabetes. It was noted that genes involved in inflammatory pathway are differentially expressed both in obesity and type 2 diabetes. These results suggest that genes concerned with carbohydrate, lipid and amino acid metabolic pathways, neuronal function and inflammation play a significant role in the pathobiology of obesity and type 2 diabetes.
 ...
PMID:Gene expression profile in obesity and type 2 diabetes mellitus. 1807 24

Epidemiological studies have confirmed that benign prostatic hyperplasia (BPH) and erectile dysfunction (ED) are correlated, independent of age or comorbidities as diabetes. Although researchers have not yet established a direct causal relationship between the two problems, several pathophysiological factors may serve to explain it, which include the alteration in nitric oxide bioavailability, increased autonomic activity, a1-adrenergic receptor hyperactivity, imbalance of RhoA/Rho-kinase, and metabolic syndrome X. Men seeking care for BPH should always be screened for sexual function and complaints of ED. PDE5 inhibitors show promise as a future treatment for lower urinary tract symptoms secondary to BPH. Further investigation is required for future therapies and possible preventative strategies.
 ...
PMID:[Benign prostatic hyperplasia and erectile dysfunction: an update]. 2386 40


<< Previous 1 2 3 4