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

Epidemiological studies have shown a strong correlation between stressful events (nutritional, hormonal or environmental) in early life and development of adult diseases such as obesity, diabetes and cardiovascular failure. It is known that gestation and lactation are crucial periods for healthy growth in mammals and that the sympathoadrenal system is markedly influenced by environmental conditions during these periods. We previously demonstrated that neonatal hyperleptinaemia in rats programmes higher body weight, higher food intake and hypothalamic leptin resistance in adulthood. Using this model of programming, we investigated adrenal medullary function and effects on cardiovascular parameters in male rats in adulthood. Leptin treatment during the first 10 days of lactation (8 microg 100 g(-1) day(-1), s.c.) resulted in lower body weight (6.5%, P < 0.05), hyperleptinaemia (10-fold, P < 0.05) and higher catecholamine content in adrenal glands (18.5%, P < 0.05) on the last day of treatment. In adulthood (150 days), the rats presented higher body weight (5%, P < 0.05), adrenal catecholamine content (3-fold, P < 0.05), tyrosine hydroxylase expression (35%, P < 0.05) and basal and caffeine-stimulated catecholamine release (53% and 100%, respectively, P < 0.05). Systolic blood pressure and heart rate were also higher in adult rats (7% and 6%, respectively, P < 0.05). Our results show that hyperleptinaemia in early life increases adrenal medullary function in adulthood and that this may alter cardiovascular parameters. Thus, we suggest that imprinting factors which increase leptin and catecholamine levels during the neonatal period could be involved in development of adult chronic diseases.
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PMID:Neonatal hyperleptinaemia programmes adrenal medullary function in adult rats: effects on cardiovascular parameters. 1721 54

Retinal vasoconstriction and reduced retinal blood flow precede the onset of diabetic retinopathy. The pathophysiological mechanisms that underlie increased retinal arteriolar tone during diabetes remain unclear. Normally, local Ca(2+) release events (Ca(2+)-sparks), trigger the activation of large-conductance Ca(2+)-activated K(+)(BK)-channels which hyperpolarize and relax vascular smooth muscle cells, thereby causing vasodilatation. In the present study, we examined BK channel function in retinal vascular smooth muscle cells from streptozotocin-induced diabetic rats. The BK channel inhibitor, Penitrem A, constricted nondiabetic retinal arterioles (pressurized to 70mmHg) by 28%. The BK current evoked by caffeine was dramatically reduced in retinal arterioles from diabetic animals even though caffeine-evoked [Ca(2+)](i) release was unaffected. Spontaneous BK currents were smaller in diabetic cells, but the amplitude of Ca(2+)-sparks was larger. The amplitudes of BK currents elicited by depolarizing voltage steps were similar in control and diabetic arterioles and mRNA expression of the pore-forming BKalpha subunit was unchanged. The Ca(2+)-sensitivity of single BK channels from diabetic retinal vascular smooth muscle cells was markedly reduced. The BKbeta1 subunit confers Ca(2+)-sensitivity to BK channel complexes and both transcript and protein levels for BKbeta1 were appreciably lower in diabetic retinal arterioles. The mean open times and the sensitivity of BK channels to tamoxifen were decreased in diabetic cells, consistent with a downregulation of BKbeta1 subunits. The potency of blockade by Pen A was lower for BK channels from diabetic animals. Thus, changes in the molecular composition of BK channels could account for retinal hypoperfusion in early diabetes, an idea having wider implications for the pathogenesis of diabetic hypertension.
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PMID:Diabetes downregulates large-conductance Ca2+-activated potassium beta 1 channel subunit in retinal arteriolar smooth muscle. 1729 77

Caffeine, widely consumed in beverages, and many xanthine analogs have had a major impact on biomedical research. Caffeine and various analogs, the latter designed to enhance potency and selectivity toward specific biological targets, have played key roles in defining the nature and role of adenosine receptors, phosphodiesterases, and calcium release channels in physiological processes. Such xanthines and other caffeine-inspired heterocycles now provide important research tools and potential therapeutic agents for intervention in Alzheimer's disease, asthma, cancer, diabetes, and Parkinson's disease. Such compounds also have activity as analgesics, antiinflammatories, antitussives, behavioral stimulants, diuretics/natriuretics, and lipolytics. Adverse effects can include anxiety, hypertension, certain drug interactions, and withdrawal symptoms.
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PMID:Caffeine analogs: biomedical impact. 1751 58

Nutrients interact with the human genome to modulate molecular pathways that may become disrupted, resulting in an increased risk of developing various chronic diseases. Genetic polymorphisms affect the metabolism of dietary factors, which in turn affects the expression of genes involved in a number of important metabolic processes. Genetic polymorphisms affecting nutrient metabolism may explain some of the inconsistencies among epidemiological studies relating diet to chronic diseases such as cancer, diabetes, rheumatoid arthritis, osteoporosis and cardiovascular disease. Understanding how genetic variations influence nutrient digestion, absorption, transport, biotransformation, uptake and elimination will provide a more accurate measure of exposure to the bioactive food ingredients ingested. Furthermore, genetic polymorphisms in the targets of nutrient action such as receptors, enzymes or transporters could alter molecular pathways that influence the physiological response to dietary interventions. Among the candidate genes with functional variants that affect nutrient metabolism are those that code for xenobiotic-metabolizing enzymes (also called drug-metabolizing enzymes). These enzymes are involved in the phase I and II biotransformation reactions that produce metabolites with either increased or decreased biological activity compared to the parent compound. A number of dietary factors are known to alter the expression of these genes that, in turn, metabolize a vast array of foreign chemicals including dietary factors such as antioxidants, vitamins, phytochemicals, caffeine, sterols, fatty acids and alcohol. Knowledge of the genetic basis for the variability in response to these dietary factors should result in a more accurate measure of exposure of target tissues of interest to these compounds and their metabolites. Examples of how 'slow' and 'fast' metabolizers respond differently to the same dietary exposures will be discussed. Identifying relevant diet-gene interactions will benefit individuals seeking personalized dietary advice as well as improve public health recommendations by providing sound scientific evidence linking diet and health.
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PMID:Nutrigenetics. 1768 98

The purpose of this study was to explore the association of serum caffeine concentrations with serum glucose levels in caffeine-drug users and non-users, aiming at the chronic effects of caffeine on glucose metabolism in comparison with known acute effects of caffeine. Eight hundred and fourteen caffeine-drug users and 623 non-users were identified from German National Health Surveys. Their serum caffeine concentrations and glucose levels were measured. The associations of caffeine concentrations with glucose levels were established by correlation analysis and multivariable regression analysis in caffeine-drug users and non-users separately. Antidiabetic therapy was considered. Caffeine concentrations were closely positively correlated to serum glucose levels in caffeine-drug users (Spearman r = 0.117, p = 0.001; partial r = 0.102, p = 0.020) particularly in women (Spearman r = 0.155, p < 0.001; partial r = 0.150, p = 0.005) although the correlation was weak as shown by multivariable regression analysis. The serum glucose levels were significantly higher (5.403 +/- 0.033 vs. 5.306 +/- 0.037 mmol/l) whereas the magnesium level was significantly lower (0.8941 +/- 0.0026 vs. 0.9024 +/- 0.0030 mmol/l) in caffeine-drug users than in non-users. No associations of caffeine concentrations with serum glucose levels were found in any groups of caffeine-drug non-users in our study. Whereas acute intake of caffeine-drugs may impair glucose metabolism, chronic intake of caffeine exclusively from diet has little effects on glucose metabolism and therefore may not contribute to the risk reduction of type 2 diabetes that was found in recent coffee consumption studies.
Diabetes Obes Metab 2007 Sep
PMID:Association of serum caffeine concentrations with serum glucose levels in caffeine-drug users and non-users - results of German National Health Surveys. 1769 66

Isolated diastolic dysfunction is found in almost half of asymptomatic patients with well-controlled diabetes and may precede diastolic heart failure. However, mechanisms that underlie diastolic dysfunction during diabetes are not well understood. We tested the hypothesis that isolated diastolic dysfunction is associated with impaired myocardial Ca(2+) handling during type 1 diabetes. Streptozotocin-induced diabetic rats were compared with age-matched placebo-treated rats. Global left ventricular myocardial performance and systolic function were preserved in diabetic animals. Diabetes-induced diastolic dysfunction was evident on Doppler flow imaging, based on the altered patterns of mitral inflow and pulmonary venous flows. In isolated ventricular myocytes, diabetes resulted in significant prolongation of action potential duration compared with controls, with afterdepolarizations occurring in diabetic myocytes (P < 0.05). Sustained outward K(+) current and peak outward component of the inward rectifier were reduced in diabetic myocytes, while transient outward current was increased. There was no significant change in L-type Ca(2+) current; however, Ca(2+) transient amplitude was reduced and transient decay was prolonged by 38% in diabetic compared with control myocytes (P < 0.05). Sarcoplasmic reticulum Ca(2+) load (estimated by measuring the integral of caffeine-evoked Na(+)-Ca(2+) exchanger current and Ca(2+) transient amplitudes) was reduced by approximately 50% in diabetic myocytes (P < 0.05). In permeabilized myocytes, Ca(2+) spark amplitude and frequency were reduced by 34 and 20%, respectively, in diabetic compared with control myocytes (P < 0.05). Sarco(endo)plasmic reticulum Ca(2+)-ATPase-2a protein levels were decreased during diabetes. These data suggest that in vitro impairment of Ca(2+) reuptake during myocyte relaxation contributes to in vivo diastolic dysfunction, with preserved global systolic function, during diabetes.
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PMID:Mechanisms of impaired calcium handling underlying subclinical diastolic dysfunction in diabetes. 1776 17

Erectile dysfunction is common among individuals with Parkinson's disease, but it is unknown whether it precedes the onset of the classic features of Parkinson's disease. To address this question, the authors examined whether erectile dysfunction was associated with Parkinson's disease risk in the Health Professionals Follow-up Study. Analyses included 32,616 men free of Parkinson's disease at baseline in 1986 who in 2000 completed a retrospective questionnaire with questions on erectile dysfunction in different time periods. Relative risks were computed using Cox proportional hazards models adjusting for age, smoking, caffeine intake, history of diabetes, and other covariates. Among men who reported their erectile function before 1986, 200 were diagnosed with Parkinson's disease during 1986-2002. Men with erectile dysfunction before 1986 were 3.8 times more likely to develop Parkinson's disease during the follow-up than were those with very good erectile function (relative risk = 3.8, 95% confidence interval: 2.4, 6.0; p < 0.0001). Multivariate-adjusted relative risks of Parkinson's disease were 2.7, 3.7, and 4.0 (95% confidence interval: 1.4, 11.1; p = 0.008) for participants with first onset of erectile dysfunction (before 1986) at 60 or more, 50-59, and less than 50 years of age, respectively, relative to those without erectile dysfunction. In conclusion, in this retrospective analysis in a large cohort of men, the authors observed that erectile dysfunction was associated with a higher risk of developing Parkinson's disease.
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PMID:Erectile function and risk of Parkinson's disease. 1787 83

With an increasing number of studies describing the negative correlation of coffee consumption and the risk for type 2 diabetes mellitus, we were compelled to elucidate the nutrients which bring pharmacological effects on risk reduction for diabetes. In this review, the author's interest is focused on chlorogenic and caffeic acids derived from lightly roasted coffee beans, as well as nicotinic acid, volatile Maillard reaction products (vMRPs), and another structurally unknown compound contained in heavily roasted beans. Caffeine is a common compound in both lightly and heavily roasted beans and its anti-inflammatory effects on degenerative diseases such as diabetes mellitus has been reevaluated recently. The prophylactic effects of coffee on diabetes involve pleiotropy of plural components in accordance to the degree of the roasting. A new concept of nutritional blended coffee may be important to optimize the prophylactic effects of coffee on lowering the risk factors of diabetes and delaying the progress of diabetes complications as well.
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PMID:[Pharmacological bases of coffee nutrients for diabetes prevention]. 1797 58

The present study assessed the relationship between coffee consumption and mortality in a home-dwelling elderly population. A population-based cohort of 817 men and women born in 1920 or earlier and living in northern Finland provided complete data on daily coffee consumption and other variables at the baseline examination in 1991-1992. Deaths were monitored through to the end of 2005 by national death certificates, resulting in 6960 person-years of follow-up. Hazard rate ratios for mortality by daily coffee intake were estimated by Poisson regression models adjusted for some known predictors of mortality. During 14.5 years of follow-up, 623 deaths occurred. The total mortality rate was inversely related to the number of cups (average volume, 125 ml) of coffee consumed daily. After adjustment for age, sub-period of follow-up, sex, marital status, basic educational level, previous occupational group, current smoking, BMI, history of myocardial infarction, self-rated health and presence of diabetes, cognitive impairment or physical disability, the estimated relative risk reduction of total mortality per an increment of one more cup of coffee per d reported at baseline was 4 (95% CI 0, 8) %. The observed associations between coffee consumption and mortality from CVD, cancer, and other or unknown causes, respectively, were qualitatively similar to that of total mortality but the estimates were less precise. The effect of coffee consumption at baseline appeared to attenuate after 10 years since the start of follow-up. The present study provides evidence for daily (caffeine-containing) coffee intake being inversely associated with mortality in the elderly.
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PMID:Coffee consumption and mortality in a 14-year follow-up of an elderly northern Finnish population. 1806 26

To test whether the beneficial effects of coffee consumption in metabolism might be explained by changes in circulating levels of adiponectin, we evaluated self-reported habitual coffee and tea consumption and caffeine intake as predictors of plasma adiponectin concentrations among 982 diabetic and 1,058 nondiabetic women without cardiovascular disease from the Nurses' Health Study. Women with and without diabetes who drank >or=4 cups of coffee per day had significantly higher adiponectin concentrations than those who didn't drink coffee regularly (7.7 vs. 6.1 microg/ml, respectively, in diabetic women, P = 0.004; 15.0 vs. 13.2 microg/ml in nondiabetic women, P = 0.04). Similar associations were observed for caffeine intake. We confirm previously reported inverse associations of coffee consumption with inflammatory markers, C-reactive protein, and tumor necrosis factor-alpha receptor II. Adjustment for adiponectin did not weaken these associations, and adjustment for inflammatory markers did not attenuate the association between coffee consumption and adiponectin concentrations. High consumption of caffeine-containing coffee is associated with higher adiponectin and lower inflammatory marker concentrations.
Diabetes Care 2008 Mar
PMID:Coffee consumption is associated with higher plasma adiponectin concentrations in women with or without type 2 diabetes: a prospective cohort study. 1844 26


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