Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The association between insulin resistance (IR) and depression is a subject of growing research interest, especially as previous population-based studies have presented conflicting findings. The present study extends our understanding about the putative impact of the severity of depressive symptoms on this association and it provides further epidemiological evidence in support of earlier findings, suggesting that the association between IR and depression is present already in young adult males. To determine the impact of the severity of depressive symptoms on the putative association between IR and depression in young adult males, we were given access to the Northern Finland 1966 Birth Cohort database. During the 31-year follow-up survey of this genetically homogeneous birth cohort, IR was assessed by 'Qualitative Insulin Sensitivity Check Index' (QUICKI), and severity of depressive symptoms by 'Hopkins' Symptom Checklist-25' (HSCL-25). This study involved 2,609 male cohort members with complete variable information. In men, the means of the QUICKI-values decreased (i.e., IR increased) in line with the increased severity of depressive symptoms as assessed by HSCL-25 subgroups (analysis of covariance P-value for trend, P=0.003). In multivariate generalized logistic regression analyses, after adjusting for confounders, IR was positively associated with current severe depressive symptoms, the odds ratio (OR) being over threefold (adjusted OR 3.15, 95% confidence interval 1.48-6.68) and the value of OR increased in parallel with a tighter definition of IR (P-value for trend=0.007). The results indicate that in young males, a positive association exists specifically with severe depressive symptoms.
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PMID:Depressive symptoms and insulin resistance in young adult males: results from the Northern Finland 1966 birth cohort. 1670 75

Insulin is best known for its role in peripheral glucose homeostasis. Less studied, but not less important, is its role in the central nervous system. Insulin and its receptor are located in the central nervous system and are both implicated in neuronal survival and synaptic plasticity. Interestingly, over the past few years it has become evident that the effects of insulin, on neuronal survival and synaptic plasticity, are mediated by a common signal transduction cascade, which has been identified as "the PI3K route". This route has turned out to be a major integrator of insulin signaling in the brain. A pronounced feature of this insulin-activated route is that it promotes survival by directly inactivating the pro-apoptotic machinery. Interestingly, it is this same route that is required for the induction of long-term potentiation and depression, basic processes underlying learning and memory. This leads to the hypothesis that the PI3K route forms a direct link between learning and memory and neuronal survival. The implications of this hypothesis are far reaching, since it provides an explanation why insulin has beneficial effects on learning and memory and how synaptic activity can prevent cellular degeneration. Applying this knowledge may provide novel therapeutic approaches in the treatment of neurodegenerative diseases such as Alzheimer's disease.
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PMID:Insulin signaling in the central nervous system: learning to survive. 1691 71

Diet-induced milk fat depression in dairy cows has been known for many years and several theories have been proposed. One that continues to receive support is the glucogenic-insulin theory. Previous studies testing this theory using a hyperinsulinemic-euglycemic clamp have had variable results attributable to variability in the use of body fat reserves as a source of milk fatty acids. Our objective was to test the glucogenic-insulin theory using cows immediately postpartum, a period when the use of body fat for milk fat synthesis is greatest. During wk 2 postpartum, 5 cows were given a 2-d baseline period and then clamped for 4 d. Insulin was increased more than 2-fold during the clamp while the blood glucose concentration was maintained. Milk yield was not altered by administration of the clamp (38.7 vs. 39.0 +/- 1.4 kg/d); however, the milk fat percentage and yield were reduced by 27% and plasma nonesterified fatty acids were reduced by 68%. Analysis of the milk fatty acid composition revealed that the decrease in milk fat yield during use of the clamp was almost exclusively due to reductions in preformed fatty acids; this is the exact opposite of what is observed with diet-induced milk fat depression. Therefore, our results do not support the glucogenic-insulin theory of diet-induced milk fat depression. The results further indicated that reductions in milk fat observed previously with hyperinsulinemic-euglycemic clamps or with glucose or propionate infusions were most likely consequences of the ability of insulin to inhibit lipolysis, thereby limiting the mammary availability of preformed fatty acids mobilized from body reserves.
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PMID:Short communication: Regulation of milk fat yield and fatty acid composition by insulin. 1703 3

Insulin resistance is a metabolic abnormality that underlies Type 2 diabetes, the metabolic syndrome and cardiovascular disease, but it may also be associated with more global health deficits. This study assessed associations of insulin resistance with health-related quality of life (HRQoL) in different domains of physical and mental health in a large elderly population study. Cross-sectional data of 1212 participants from the Hertfordshire Cohort Study were analysed. Insulin resistance was assessed by the homeostatic model assessment (HOMA-IR), and HRQoL was measured using the SF-36 health survey. Poor HRQoL was defined by a score lower than the sex-specific 10th percentile of each scale, and logistic regressions yielded odds ratios in relation to the HOMA-IR scores. Subsequent analyses adjusted for the influence of age, smoking, alcohol consumption, social class, BMI, coronary heart disease and depression. Results showed an increase in poor HRQoL with an increase in HOMA-IR scores for physical functioning (OR = 2.29; CI: 1.67-3.13), vitality (OR = 1.45; CI: 1.05-2.00), and general health (OR = 1.62; CI: 1.19-2.21). In men, but not in women, associations with physical functioning were independent of confounding variables. The results indicate that insulin resistance is associated with poor HRQoL in domains of physical health, but not in domains of mental health.
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PMID:Specific associations of insulin resistance with impaired health-related quality of life in the Hertfordshire Cohort Study. 1709 61

Insulin and Insulin-Growth-Factor-like (IGF) signaling pathways are well known longevity pathways in nematodes, insects and mammals. To our knowledge, there are no systematic pharmacological studies evaluating the anti-aging properties of medications that target this pathway in Drosophila. Although there are no published data implicating an anti-aging role for these compounds in Drosophila, we hypothesized that their promising pharmacological profile might decrease mortality. However, the decrease in mortality could be due to a number of potential artifacts and confounds such as fecundity depression, decrease in metabolic rate, or CNS depression. Therefore, the mere finding that a compound decreases mortality does not qualify it as an anti-aging compound. In this study, we evaluated the anti-aging properties of four compounds that might target the insulin signaling pathway in Drosophila. Once it was established that the compound decreased mortality, we proceeded to evaluate possible confounding factors that could have contributed to the mortality reduction. We show that only piolglitazone displayed anti-aging properties. At present, we do not have a mechanistic explanation for this pharmacological disparity.
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PMID:Pioglitazone: an anti-diabetic compound with anti-aging properties. 1762 57

Adiponectin is an adipocyte-specific secretory protein that circulates in serum as three oligomeric complexes known as the high, medium and low molecular weight form (HMW, MMW and LMW). HMW adiponectin has been suggested to be a better predictor of metabolic variables, and it was recently reported that the ratio of HMW to total adiponectin or to LMW, not the absolute amount of plasma adiponectin, might be crucial in determining insulin sensitivity. Insulin resistance (IR) is considered to be a primary component of vascular risk factors. Although the association of depression with atherosclerotic vascular diseases has been well documented, the contribution of IR to the evolution and progression of depression-associated vascular morbidity and mortality remains unknown. The current preliminary study showed that the ratio of HMW to total adiponectin or to LMW, not the absolute amount of plasma adiponectin, was negatively associated with depression severity in healthy elderly subjects without metabolic syndrome. This pilot study supports a promising role of adiponectin multimer distribution for clarifying the pathophysiological mechanism by which depression is associated with increased risk for IR, leading to cardiovascular disease, metabolic syndrome or type 2 diabetes.
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PMID:Adiponectin multimer distribution, not absolute amount of plasma, correlates with depression severity in healthy elderly subjects. 1776 80

The effects of the primary biologically active conjugated linoleic acid (CLA) isomers (cis-9, trans-11 and trans-10, cis-12; 15-150microM) on growth and survival of the bovine mammary cell-line, Mac-T, were evaluated using cell enumeration and TUNEL assay. Previous studies have shown that high concentrations of CLA induced severe milk fat depression and have had negative effects on milk yield and composition whereas the impact of lower doses has been a modest depression in milk fat percent. In this study, we show that increasing concentrations of both CLA isomers had negative impacts on cell growth, including reduced cell number at concentrations of 35microM and above (P<0.05) and a two-fold increase in induction of apoptosis in the mammary cells. Changes in cell morphology occurred with large vacuole-like structures in the cytoplasm, nuclear shrinkage and changes of nuclear shape to kidney shape. Insulin did not significantly affect apoptosis in CLA-treated cells. In addition, the effect of increased doses of CLA and the interaction of CLA and insulin on the bovine stearoyl Co-A desaturase (Scd) gene promoter was also analyzed. While a significant difference in the Scd promoter transcriptional activity was not observed in cells treated with different concentrations of CLA, insulin significantly enhanced Scd promoter activity in CLA-treated cells. Our in vitro data support the hypothesis that high levels of CLA may induce in vivo apoptosis in the mammary gland.
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PMID:Effect of conjugated linoleic acid on bovine mammary cell growth, apoptosis and stearoyl Co-A desaturase gene expression. 1795 32

The authors investigated silent myocardial ischemia in unselected consecutive middle-aged asymptomatic patients with type 2 diabetes without any evidence of coronary heart disease documented by treadmill exercise test. Ninety asymptomatic patients with type 2 diabetes (48 men; mean age: 49 +/-6 years) were included in the study. Mean duration of diabetes in the study group was 4 +/-4.2 years (range 1 to 21 years); 38% of the study population, diabetes duration was only 1 year). All patients were subjected to treadmill exercise test with Bruce protocol. A positive test was noted in 4 of 90 (4%) study patients. Two male patients (4%) and 2 (4%) women patients developed exercise-induced ST-segment depression, but none had concomitant chest pain. Diabetics with silent myocardial ischemia were older (55 +/-3 years vs 49 +/-6 years, p = 0.04) than those without silent myocardial ischemia. Also, diabetics with silent myocardial ischemia had higher fibrinogen level (372 +/-51 vs 307 +/-71 mg/dL, p = 0.04) than diabetics without silent myocardial ischemia. In treadmill exercise test, diabetics with silent myocardial ischemia had lower total exercise time and peak workload (375 +/-30 vs 474 +/-115 seconds, p = 0.04; 7.3 +/-0.5 vs 8.9 +/-1.9, p = 0.04, respectively) than without silent myocardial ischemia. Insulin resistance is associated with a variety of atherosclerosis risk factors. Exercise test findings show increased cardiac sympathetic activity and parasympathetic withdrawal in increased insulin resistance.
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PMID:Silent myocardial ischemia in middle-aged asymptomatic patients with type 2 diabetes in Turkish population. 1802 35

Protein kinase C (PKC) is involved in synaptic remodeling, induction of protein synthesis, and many other processes important in learning and memory. Activation of neuronal protein kinase C correlates with, and may be essential for, all phases of learning, including acquisition, consolidation, and reconsolidation. Protein kinase C activation is closely tied to hydrolysis of membrane lipids. Phospholipases C and A2 produce 1,2-diacylglycerol and arachidonic acid, which are direct activators of protein kinase C. Phospholipase C also produces inositol triphosphate, which releases calcium from internal stores. Protein kinase C interacts with many of the same pathways as insulin; therefore, it should not be surprising that insulin signaling and protein kinase C activation can both have powerful effects on memory storage and synaptic remodeling. However, investigating the possible roles of insulin in memory storage can be challenging, due to the powerful peripheral effects of insulin on glucose and the low concentration of insulin in the brain. Although peripheral for insulin, synthesized in the beta-cells of the pancreas, is primarily involved in regulating glucose, small amounts of insulin are also present in the brain. The functions of this brain insulin are inadequately understood. Protein kinase C may also contribute to insulin resistance by phosphorylating the insulin receptor substrates required for insulin signaling. Insulin is also responsible insulin-long term depression, a type of synaptic plasticity that is also dependent on protein kinase C. However, insulin can also activate PKC signaling pathways via PLC gamma, Erk 1/2 MAP kinase, and src stimulation. Taken together, the available evidence suggests that the major impact of protein kinase C and its interaction with insulin in the mature, fully differentiated nervous system appears to be to induce synaptogenesis, enhance memory, reduce Alzheimer's pathophysiology, and stimulate neurorepair.
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PMID:Insulin, PKC signaling pathways and synaptic remodeling during memory storage and neuronal repair. 1840 35

The central angiotensin system plays a crucial role in cardiovascular regulation. More recently, angiotensin peptides have been implicated in stress, anxiety, depression, cognition, and epilepsy. Angiotensin II (Ang II) exerts its actions through AT(1) and AT(2) receptors, while most actions of its metabolite Ang IV were believed to be independent of AT(1) or AT(2) receptor activation. A specific binding site with high affinity for Ang IV was discovered and denominated "AT(4) receptor". The beneficiary effects of AT(4) ligands in animal models for cognitive impairment and epileptic seizures initiated the search for their mechanism of action. This proved to be a challenging task, and after 20 years of research, the nature of the "AT(4) receptor" remains controversial. Insulin-regulated aminopeptidase (IRAP) was first identified as the high-affinity binding site for AT(4) ligands. Recently, the hepatocyte growth factor receptor c-MET was also proposed as a receptor for AT(4) ligands. The present review focuses on the effects of Ang II and Ang IV on synaptic transmission and plasticity, learning, memory, and epileptic seizure activity. Possible interactions of Ang IV with the classical AT(1) and AT(2) receptor subtypes are evaluated, and other potential mechanisms by which AT(4) ligands may exert their effects are discussed. Identification of these mechanisms may provide a valuable target in the development in novel drugs for the treatment of cognitive disorders and epilepsy.
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PMID:Ang II and Ang IV: unraveling the mechanism of action on synaptic plasticity, memory, and epilepsy. 1904 May 56


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