Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apolipoprotein A-IV is considered to play a role in triglyceride-rich lipoprotein metabolism, in reverse cholesterol transport, and in facilitation of CETP (Cholesterolyl Ester Transfer Protein) activity. Moreover, apoA-IV is genetically polymorphic in humans, in whom two major isoproteins (apoA-IV 1 and apoA-IV 2) are present and have differences that influence the apoA-IV phenotype in lipid metabolism. In non-insulin-dependent-diabetes, increased apoA-IV levels are found, mainly related to hypertriglyceridemia and to a lesser extent to HDL cholesterol level; apoA-IV phenotype distribution is not different from controls; in the control population, the potential protective lipid profile (characterized by increased HDL and HDL2 cholesterol levels) related to the apoA-IV 1-2 phenotype, is no longer found in NIDDM patients (the metabolic state of NIDDM appears to have effected the potential protective lipid profile related to the apoA-IV 1-2 phenotype); and plasma apoA-IV levels is associated with increased prevalence for macrovascular disease. In non-insulin-dependent diabetes treated with insulin, apoA-IV levels are increased. Unlike results for NIDDM patients undergoing oral treatment, the increase in apoA-IV level is not related to hypetriglyceridemia, so that the effect on lipid metabolism may be different.
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PMID:Apolipoprotein A-IV in diabetes mellitus. 762 79

Apolipoprotein A-IV (apoA-IV) might play an important role in lipoprotein metabolism, including modulation of triglyceride-rich lipoprotein catabolism, reverse cholesterol transport and cholesteryl ester transfer protein (CETP) activity. Increased apoA-IV levels have been reported in plasma from NIDDM patients. The aim of the present study was to look for a possible association between plasma apoA-IV level and prevalence of macrovascular disease in NIDDM. One hundred and thirty-six NIDDM patients were studied (71 men, 65 women). Macrovascular disease was assessed in each patient by a standardized questionnaire, physical examination, resting electrocardiogram (ECG), and laboratory evaluation (ankle/arm blood pressure ratio, continuous wave Doppler velocimetry). Moreover, patients without any history of coronary heart disease and showing a normal resting ECG underwent a bicycle exercise test or a dipyridamole thallium scintigraphy to detect possible silent myocardial ischemia. Among the 136 NIDDM patients, 56 had macrovascular disease. ApoA-IV levels were significantly higher in NIDDM patients with macrovascular disease than in NIDDM patients without macrovascular disease (20.9 +/- 8.6 vs. 13.3 +/- 5.3 mg/dl; P < 0.001). The influence of different factors, such as age, BMI, cigarette smoking, hypertension, total cholesterol, triglycerides, HDL cholesterol, apoA-IV level, apoA-IV phenotype, fasting glycemia, fasting C-peptide, and microalbuminuria, on the prevalence of macrovascular disease was analyzed using a logistic regression model. In the univariate analysis, apoA-IV level (P < 0.00001), age (P = 0.0087), hypertension (P = 0.012), microalbuminuria (P = 0.018), triglycerides (P = 0.02), and fasting C-peptide (P = 0.03) were positively associated with macrovascular disease. In the multivariate analysis, macrovascular disease was positively associated only with apoA-IV (P < 0.0001) and age (P = 0.003) and negatively associated with HDL cholesterol (P = 0.013). These results indicate that increased plasma apoA-IV level is associated with an increased prevalence of macrovascular disease in NIDDM. Moreover, apoA-IV, in NIDDM patients, appears to be a better marker for macrovascular disease than triglycerides.
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PMID:Macrovascular disease is associated with increased plasma apolipoprotein A-IV levels in NIDDM. 897 Oct 92

Obesity is commonly associated with high rates of cardiovascular disease (CVD). Weight loss in obese subjects reduces risk factors for CVD but this response is not uniform. Genetic factors could be involved in this variability. The 360His polymorphism of apolipoproteinA-IV (apoA-IV) influences the lipid response to fat intake, but it is unclear whether this polymorphism could contribute to lipid variability during weight loss. Therefore, we assessed the effects of an energy restricted diet (6.3 MJ) for 12 weeks on weight loss and plasma lipids according to apoA-IV genotype in 186 overweight/obese subjects (BMI mean 33+/-4.3, range 25.0-48.0 kg/m(2)). The frequency of the 360His allele was 0.083. Energy restriction for 12 weeks resulted in an average weight loss of 8. 25+/-0.28 kg. HDL-C increased 5.4% in subjects with the apoA-IV-1/1 genotype with weight loss compared to a 2.6% decrease in apoA-IV-1/2 subjects (P=0.035). This was more apparent when only the subjects with type 2 diabetes (n=57) were analyzed (P=0.003). ApoA-IV genotype was not related to change in total cholesterol, LDL-C or triglyceride concentrations. Therefore, weight loss as a treatment to reduce CVD risk factors may be more effective in subjects with the apoA-IV-1/1 variant as compared to those with the apoA-IV-1/2 variant, especially in subjects with type 2 diabetes.
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PMID:360His polymorphism of the apolipoproteinA-IV gene and plasma lipid response to energy restricted diets in overweight subjects. 1078 50

The present study investigated genetic variation in the 3' flanking region of ApoA-I (PstI), the 3' untranslated region of ApoC-III (SstI) and intron 2 of ApoA-IV (XbaI) in 435 type 2 diabetes mellitus patients, divided according to the presence or absence of coronary heart disease (CHD). Uncommon allele frequencies (P2, S2, X2) were 17.5%, 32.5%, 16.2% and 29.5%, 17.9%, 13.8% in patients with and without CHD, respectively. Linkage disequilibrium (D' = 0.31-0.73, p<0.01) was observed in all diallelic pairs except XbaI/PstI and XbaI/SstI in patients having CHD. Haplotype analysis revealed that P1-S2-X1 is a susceptibility haplotype that increases the risk of CHD in diabetes (OR 2.85, CI 1.51-5.61), exacerbating risk (OR 3.57, CI 1.81-7.45) even after adjustment for confounders. The findings in the present study suggest that each unit of P1-S2-X1 in diabetes increases the risk of CHD by a factor of 1.37+/-0.307 (beta + SE), which is manifest in its multiplicative mode.
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PMID:The ApoAI-CIII-AIV gene cluster and its relation to lipid levels in type 2 diabetes mellitus and coronary heart disease: determination of a novel susceptible haplotype. 1765 46

Insulin resistance is a risk factor for type 2 diabetes mellitus. We investigated the effect of ApoA-IV on glucose uptake in the adipose and muscle tissues of mice and cultured 3T3-L1 adipocytes. We found that treatment with ApoA-IV lowered fasting blood glucose in both WT and diabetic KKAy mice by increasing glucose uptake in cardiac muscle, white adipose tissue, and brown adipose tissue through a mechanism that was partially insulin independent. Cell culture experiments showed that ApoA-IV improved glucose uptake in adipocytes in the absence of insulin by upregulating GLUT4 translocation by PI3K mediated activation of Akt signaling pathways. Considering our previous finding that ApoA-IV treatment enhanced pancreatic insulin secretion, these results suggests that ApoA-IV acts directly upon adipose tissue to improve glucose uptake and indirectly via insulin signaling. Our findings warrant future studies to identify the receptor for ApoA-IV and the downstream targets of PI3K-Akt signaling that regulate glucose uptake in adipocytes as potential therapeutic targets for treating insulin resistance.
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PMID:ApoA-IV improves insulin sensitivity and glucose uptake in mouse adipocytes via PI3K-Akt Signaling. 2811 4

We examined the effect of mild hyperglycemia on high-density lipoprotein (HDL) metabolism and kinetics in diet-controlled subjects with type 2 diabetes (T2D). 2H2O-labeling coupled with mass spectrometry was applied to quantify HDL cholesterol turnover and HDL proteome dynamics in subjects with T2D (n = 9) and age- and BMI-matched healthy controls (n = 8). The activities of lecithin-cholesterol acyltransferase (LCAT), cholesterol ester transfer protein (CETP), and the proinflammatory index of HDL were quantified. Plasma adiponectin levels were reduced in subjects with T2D, which was directly associated with suppressed ABCA1-dependent cholesterol efflux capacity of HDL. The fractional catabolic rates of HDL cholesterol, apolipoprotein A-II (ApoA-II), ApoJ, ApoA-IV, transthyretin, complement C3, and vitamin D-binding protein (all p < 0.05) were increased in subjects with T2D. Despite increased HDL flux of acute-phase HDL proteins, there was no change in the proinflammatory index of HDL. Although LCAT and CETP activities were not affected in subjects with T2D, LCAT was inversely associated with blood glucose and CETP was inversely associated with plasma adiponectin. The degradation rates of ApoA-II and ApoA-IV were correlated with hemoglobin A1c. In conclusion, there were in vivo impairments in HDL proteome dynamics and HDL metabolism in diet-controlled patients with T2D.
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PMID:Temporal Dynamics of High-Density Lipoprotein Proteome in Diet-Controlled Subjects with Type 2 Diabetes. 3223 66