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)

We examined whether macrophages from men and women with Type 2 diabetes mellitus (T2DM) exhibited differences in expression of key genes involved in fatty acid metabolism and in fatty acid composition compared with macrophages from non-diabetic controls. Peripheral blood monocytes from subjects with T2DM (n=9) and non-diabetic controls (n=10) were differentiated into macrophages in 10% autologous serum and normal (5mM) or high (22mM) glucose. Levels of PPARalpha, PPARgamma, LXRalpha, SCD and ABCA1 mRNAs were similar in macrophages from subjects with T2DM and controls. At 5mM glucose, macrophage stearic acid (C18:0) was 12.6+/-1.0% of total fatty acids for T2DM compared with 18.1+/-2.0% for controls (p=0.03). Macrophage linoleic acid (C18:2) was 15.5+/-0.8% for T2DM and 9.3+/-2.0% for controls (p=0.005). The ratio of macrophage stearic acid (C18:0)/oleic acid (C18:1) was 0.29 [0.25,0.48] for T2DM versus 0.54 [0.36,0.82] for controls (p=0.04). Compared with non-diabetic controls, macrophages from men and women with T2DM had significantly different fatty acid profiles consistent with increased stearoyl-CoA desaturase (SCD) activity and increased C18:2 accumulation. This pattern of altered macrophage fatty acid composition may be relevant to diabetic atherogenesis.
Diabetes Res Clin Pract 2007 Mar
PMID:Monocyte-derived macrophages from men and women with Type 2 diabetes mellitus differ in fatty acid composition compared with non-diabetic controls. 1690 84

High nonesterified fatty acid (NEFA) concentrations, as observed in the metabolic syndrome, trigger apoptosis of human umbilical vein endothelial cells. Since endothelial apoptosis may contribute to atherothrombosis, we studied the apoptotic susceptibility of human coronary artery endothelial cells (HCAECs) toward selected NEFAs and the underlying mechanisms. HCAECs were treated with single or combined NEFAs. Apoptosis was quantified by flow cytometry, nuclear factor kappaB (NFkappaB) activation by electrophoretic mobility shift assay, and secreted cytokines by enzyme-linked immunosorbent assay. Treatment of HCAECs with saturated NEFAs (palmitate and stearate) increased apoptosis up to fivefold (P < 0.05; n = 4). Unsaturated NEFAs (palmitoleate, oleate, and linoleate) did not promote apoptosis but prevented stearate-induced apoptosis (P < 0.05; n = 4). Saturated NEFA-induced apoptosis neither depended on ceramide formation nor on oxidative NEFA catabolism. However, NEFA activation via acyl-CoA formation was essential. Stearate activated NFkappaB and linoleate impaired stearate-induced NFkappaB activation. Pharmacological inhibition of NFkappaB and inhibitor of kappaB kinase (IKK) also blocked stearate-induced apoptosis. Finally, the saturated NEFA effect on NFkappaB was not attributable to NEFA-induced cytokine production. In conclusion, NEFAs display differential effects on HCAEC survival; saturated NEFAs (palmitate and stearate) are proapoptotic, and unsaturated NEFAs (palmitoleate, oleate, and linoleate) are antilipoapoptotic. Mechanistically, promotion of HCAEC apoptosis by saturated NEFA requires acyl-CoA formation, IKK, and NFkappaB activation.
Diabetes 2006 Nov
PMID:Saturated, but not unsaturated, fatty acids induce apoptosis of human coronary artery endothelial cells via nuclear factor-kappaB activation. 1706 51

Eleven monoglycerides (MG), 1-monopalmitin (1), glyceryl 1-monomargarate (2), 1-monostearin (3), glyceryl 1-monononadecylate ( 4), glyceryl 1-monoarachidate (5), glyceryl 1-monobehenate (6), glyceryl 1-monotricosanoate (7), glyceryl 1-monotetracosanoate (8), glyceryl 1-monopentacosanoate (9), glyceryl 1-monohexacosanoate (10) and glyceryl 1-monooctacosanoate (11), together with five fatty acids (FA), lauric acid (12), myristic acid (13), pentadecanoic acid (14), palmitic acid (15) and stearic acid (16) were isolated of the root of IBERVILLEA SONORAE Greene (Cucurbitaceae). Their structures were determined by spectroscopic and chemical methods as well as GC-MS analysis. The hypoglycemic activity of the dichloromethane (DCM) extract, of fractions (F1-F10 and SF1-SF5), of monoglycerides (MG) and of fatty acids (FA) mixtures obtained of the root from I. SONORAE was evaluated in normoglycemic and alloxan-induced diabetic mice. The results showed that by intraperitoneal administration the DCM extract (300 mg/kg), F9 (300 mg/kg) and SF1 (150 mg/kg) significantly reduced glucose levels in both models. For fraction SF1, the hypoglycemic activity was more pronounced than that of tolbutamide (150 mg/kg) used as control. However, neither MG (75 mg/kg) nor FA (75 mg/kg) mixtures isolated from SF1 exhibited a significant hypoglycemic effect. However, when MG and FA were combined in equal proportions (75 mg: 75 mg/kg), their effect was comparable to that of SF1. The observed activity for the DCM extract, F9, SF1 and the MG-FA mixture provides additional support for the popular use of this plant in the treatment of diabetes mellitus in Mexican traditional medicine.
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PMID:Monoglycerides and fatty acids from Ibervillea sonorae root: isolation and hypoglycemic activity. 1731 82

Defects in fatty acid translocase (FAT/CD36) have been identified as a major factor in insulin resistance and defective fatty acid and glucose metabolism. Therefore, understanding of the regulation of FAT/CD36 expression and function is important for a potential therapeutic target for type II diabetes. We differentiated 3T3-L1 preadipocytes into matured adipocytes and examined the roles of insulin and long chain fatty acids on FAT/CD36 expression and function. Our results indicate that FAT/CD36 mRNA expression was not detected at preadipocyte but was significantly increased at matured adipocyte. In fully differentiated 3T3-L1 adipocytes, insulin significantly increased FAT/CD36 mRNA and protein expression in a dose dependent manner. The free fatty acid stearic acid reduced FAT/CD36 mRNA expression while the non-metabolizable free fatty acid alpha-bromopalmitate (2-BP) significantly increased FAT/CD36 mRNA and protein expression. Isoproterenol, in contrast, dose-dependently reduced FAT/CD36 mRNA expression and increased free fatty acid release. Mechanism analysis indicated that the effect of insulin and 2-BP on the FAT/CD36 mRNA gene expression may be mediated through activation of PPAR-gamma, suggesting that FAT/CD36 may have important implications in the pathophysiology of defective fatty acid metabolism.
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PMID:Regulation of FAT/CD36 mRNA gene expression by long chain fatty acids in the differentiated 3T3-L1 cells. 1751 74

Resistin was initially identified as a protein, secreted by adipocytes, which inhibits insulin action and adipose differentiation. The three proteins homologous to resistin were identified and given the names resistin-like molecules (RELM) alpha, beta and gamma. Resistin and RELMalpha are abundantly expressed in adipose, but RELMbeta and RELMgamma are secreted mainly from the gut. Since nutrient composition greatly affects insulin sensitivity, we investigated the regulatory effects of various nutritional factors in food on the expressions of resistin family proteins. First, mice were given diets with different nutritional compositions (high-carbohydrate, high-protein and high-fat) for 2 weeks. RELMbeta mRNA expression in the intestines was markedly suppressed by the high-protein and high-carbohydrate diets, while slightly but not significantly upregulated by the high-fat diet. In the epididymal fat, resistin expression was unchanged, while RELMalpha expression was markedly decreased by the high-carbohydrate diet. Taking into consideration that humans have neither RELMalpha nor RELMgamma, our subsequent studies focused on RELMbeta expression. We used the human colon cancer cell line LS174T. Treatments with insulin and TNFalpha as well as stearic acid, a saturated free fatty acid, upregulated RELMbeta expression, while d-glucose downregulated RELMbeta. These results suggest RELMbeta expression to be regulated directly by nutrients such as glucose and saturated free fatty acids including stearic acid, as well as by hormones including insulin and TNFalpha. These regulations may play an important role in the nutrient-associated induction of insulin resistance.
Diabetes Res Clin Pract 2008 Jan
PMID:Regulation of gut-derived resistin-like molecule beta expression by nutrients. 1793 98

Previous studies from our laboratory indicated that pre-germinated brown rice (PR) contained certain unknown bioactive lipids that activated two enzymes related to diabetes: Na+/K+ATPase and homocysteine-thiolactonase. In this paper, we report on the isolation and structural characterization of the activator lipids from PR bran as acylated steryl glucosides (ASGs). The activator lipid was isolated by silica gel column chromatography, and its chemical structure was determined by NMR, GC-MS, and tandem mass spectrometry. We demonstrated that the bioactive component consists of a mixture of acylated steryl beta-glucosides. Delta8-cholesterol and 2-hydroxyl stearic acid were identified as constituents of ASGs. The steryl glucosides (SGs) subsequent to alkaline hydrolysis lost this enzyme activator activity. Soybean-derived ASGs were not active. This activity may be quite peculiar to PR-derived ASGs. Our findings suggest that the molecular species of ASG may play an important contributing role in the anti-diabetic properties of a PR diet.
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PMID:Structural analysis of novel bioactive acylated steryl glucosides in pre-germinated brown rice bran. 1858 70

Apoptosis and underlying mechanisms were evaluated in human umbilical vein endothelial cells (HUVECs), in target tissues of late diabetic vascular complications [human aortic endothelial cells (HAECs) and human retinal endothelial cells (HRECs)], and in endothelial progenitor cells (EPCs) exposed to FFAs, which are elevated in obesity and diabetes. Saturated stearic acid concentration dependently induced apoptosis that could be mediated via reduced membrane fluidity, because both apoptosis and membrane rigidity are counteracted by eicosapentaenoic acid. PUFAs triggered apoptosis at a concentration of 300 micromol/l in HUVECs, HAECs, and EPCs, but not HRECs, and, in contrast to stearic acid, involved caspase-8 activation. PUFA-induced apoptosis, but not stearic acid-induced apoptosis, strictly correlated (P < 0.01) with protein expression of E2F-1 (r = 0.878) and c-myc (r = 0.966). Lack of c-myc expression and activity owing to quiescence or transfection with dominant negative In373-Myc, respectively, renders HUVECs resistant to PUFA-induced apoptosis. Because c-myc is abundant in growing cells only, apoptosis triggered by PUFAs, but not by saturated stearic acid, obviously depends on the growth/proliferation status of the cells. Finally, this study shows that FFA-induced apoptosis depends on the vascular origin and growth/proliferation status of endothelial cells, and that saturated stearic acid-induced apoptosis and PUFA-induced apoptosis are mediated via different mechanisms.
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PMID:Different mechanisms of saturated versus polyunsaturated FFA-induced apoptosis in human endothelial cells. 1868 7

The aim of the present study was to evaluate the effect of aqueous bark extract of Helicteres isora (HI) (Sterculiaceae) on the blood glucose, plasma insulin and fatty acid composition of the total lipids in the liver, kidney and brain of control and streptozotocin (STZ) diabetic rats. The analysis of fatty acids showed that there was a significant increase in the concentrations of palmitic acid (16:1), stearic acid (18:0) and oleic acid (18:1) in the liver, kidney and brain, whereas the concentrations of linolenic acid (18:3) and arachidonic acid (20:4) were significantly decreased in STZ diabetic rats. Oral administration of the aqueous bark extract of HI (100, 200mg/kg body weight) for 30 days to diabetic rats decreased the concentrations of fatty acids, viz., palmitic, stearic, and oleic acid, whereas linolenic and arachidonic acid were elevated. These results suggest that HI exhibits antidiabetic and antihyperlipidemic effects in STZ induced diabetic rats. It also prevents the fatty acid changes produced during diabetes. The antidiabetic and antihyperlipidemic effects of HI are more potent than those of tolbutamide, as standard drug. The results of the present study indicate that HI showed an antihyperlipidemic effect in addition to its antidiabetic effect in type 2 diabetic rats.
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PMID:Influence of Helicteres isora administration for diabetes mellitus: the effect on changes in tissue fatty acid composition. 1941 Jun 28

Dietary and policy recommendations frequently focus on reducing saturated fatty acid consumption for improving cardiometabolic health, based largely on ecologic and animal studies. Recent advances in nutritional science now allow assessment of critical questions about health effects of saturated fatty acids (SFA). We reviewed the evidence from randomized controlled trials (RCTs) of lipid and non-lipid risk factors, prospective cohort studies of disease endpoints, and RCTs of disease endpoints for cardiometabolic effects of SFA consumption in humans, including whether effects vary depending on specific SFA chain-length; on the replacement nutrient; or on disease outcomes evaluated. Compared with carbohydrate, the TC:HDL-C ratio is nonsignificantly affected by consumption of myristic or palmitic acid, is nonsignificantly decreased by stearic acid, and is significantly decreased by lauric acid. However, insufficient evidence exists for different chain-length-specific effects on other risk pathways or, more importantly, disease endpoints. Based on consistent evidence from human studies, replacing SFA with polyunsaturated fat modestly lowers coronary heart disease risk, with ~10% risk reduction for a 5% energy substitution; whereas replacing SFA with carbohydrate has no benefit and replacing SFA with monounsaturated fat has uncertain effects. Evidence for the effects of SFA consumption on vascular function, insulin resistance, diabetes, and stroke is mixed, with many studies showing no clear effects, highlighting a need for further investigation of these endpoints. Public health emphasis on reducing SFA consumption without considering the replacement nutrient or, more importantly, the many other food-based risk factors for cardiometabolic disease is unlikely to produce substantial intended benefits.
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PMID:Saturated fat and cardiometabolic risk factors, coronary heart disease, stroke, and diabetes: a fresh look at the evidence. 2035 6

Obesity is currently epidemic in many countries worldwide and is strongly related to diabetes and cardiovascular disease. This study investigated the differences in metabolomic profiling between overweight/obese and normal-weight men. Overweight/obese (n=30) and age-matched, normal-weight men (n=30) were included. Anthropometric parameters, conventional metabolites, and biomarkers were measured. Metabolomic profiling was analyzed with UPLC-Q-TOF MS. Overweight/obese men showed higher levels of HOMA-IR, triglycerides, total cholesterol, and LDL-cholesterol, and lower levels of HDL-cholesterol and adiponectin than lean men. Overweight/obese men showed higher proportion of stearic acid and lower proportion of oleic acid in serum phospholipids. Additionally, overweight/obese individuals showed higher fat intake and lower ratio of polyunsaturated fatty acids to saturated fatty acids. We identified three lyso-phosphatidylcholine (lysoPC) as potential plasma markers and confirmed eight known metabolites for overweight/obesity men. Especially, overweight/obese subjects showed higher levels of lysoPC C14:0 and lysoPC C18:0 and lower levels of lysoPC C18:1 than lean subjects. Results confirmed abnormal metabolism of two branched-chain amino acids, two aromatic amino acids, and fatty acid synthesis and oxidation in overweight/obese men. Additionally, the amount of dietary saturated fat may influence the proportion of saturated fatty acids in serum phospholipids and the degree of saturation of the constituent acyl group of plasma lysoPC.
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PMID:Metabolic profiling of plasma in overweight/obese and lean men using ultra performance liquid chromatography and Q-TOF mass spectrometry (UPLC-Q-TOF MS). 2056 May 78


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