The novel adiponectin-resistin (AR) and insulin resistance (IR~AR~) indexes

Serum hypoadiponectinemia and hyperrestinemia independently links insulin resistance to type 2 diabetes (T2DM) and metabolic syndrome (MS). Thus, the aim of this study was propose a novel adiponectin-resistin (AR) index by unifying the effect of adiponectin and resistin. Then, a novel insulin resistance (IR~AR~) index was proposed by taking into account the AR index. Serum adiponectin and resistin levels as well as other insulin resistance, T2DM and MS risk factors were tested. Experimental results showed the AR index was more stronger correlated with insulin resistance risk factors and had stronger association (df=5; F=51.154; P<0.001) with T2DM and MS susceptibility rather than the serum adiponectin (df=5; F=15.680; P<0.001) and resistin (df=5; F=40.648; P<0.001) levels alone. Therefore, the AR index looks very strongly links insulin resistance to T2DM and MS. Meanwhile, the IR~AR~ index (df=5; F=78.396; P<0.001) is a potent useful index of insulin sensitivity in subjects with T2DM and MS

Lack of evidence for intermolecular epistatic interactions between adiponectin and resistin gene polymorphisms in Malaysian male subjects

Epistasis (gene-gene interaction) is a ubiquitous component of the genetic architecture of complex traits such as susceptibility to common human diseases. Given the strong negative correlation between circulating adiponectin and resistin levels, the potential intermolecular epistatic interactions between ADIPOQ (SNP+45T > G, SNP+276G > T, SNP+639T > C and SNP+1212A > G) and RETN (SNP-420C > G and SNP+299G > A) gene polymorphisms in the genetic risk underlying type 2 diabetes (T2DM) and metabolic syndrome (MS) were assessed. The potential mutual influence of the ADIPOQ and RETN genes on their adipokine levels was also examined. The rare homozygous genotype (risk alleles) of SNP-420C > G at the RETN locus tended to be co-inherited together with the common homozygous genotypes (protective alleles) of SNP+639T > C and SNP+1212A > G at the ADIPOQ locus. Despite the close structural relationship between the ADIPOQ and RETN genes, there was no evidence of an intermolecular epistatic interaction between these genes. There was also no reciprocal effect of the ADIPOQ and RETN genes on their adipokine levels, i.e., ADIPOQ did not affect resistin levels nor did RETN affect adiponectin levels. The possible influence of the ADIPOQ gene on RETN expression warrants further investigation

Novel adiponectin-resistin (AR) and insulin resistance (IRAR) indexes are useful integrated diagnostic biomarkers for insulin resistance, type 2 diabetes and metabolic syndrome: a case control study

<p>Abstract</p> <p>Background</p> <p>Adiponectin and resistin are adipokines which modulate insulin action, energy, glucose and lipid homeostasis. Meta-analyses showed that hypoadiponectinemia and hyperresistinemia are strongly associated with increased risk of insulin resistance, type 2 diabetes (T2DM), metabolic syndrome (MS) and cardiovascular disease. The aim of this study was to propose a novel adiponectin-resistin (AR) index by taking into account both adiponectin and resistin levels to povide a better indicator of the metabolic homeostasis and metabolic disorders. In addition, a novel insulin resistance (IR_AR) index was proposed by integration of the AR index into an existing insulin resistance index to provide an improved diagnostic biomarker of insulin sensitivity.</p> <p>Methods</p> <p>In this case control study, anthropometric clinical and metabolic parameters including fasting serum total adiponectin and resistin levels were determined in 809 Malaysian men (208 controls, 174 MS without T2DM, 171 T2DM without MS, 256 T2DM with MS) whose ages ranged between 40-70 years old. Significant differences in continuous variables among subject groups were confirmed by ANCOVA or MANCOVA test using 1,000 stratified bootstrap samples with bias corrected and accelerated (BCa) 95% CI. Spearman's rho rank correlation test was used to test the correlation between two variables.</p> <p>Results</p> <p>The AR index was formulated as 1+log₁₀(R₀)-log₁₀(A₀). The AR index was more strongly associated with increased risk of T2DM and MS than hypoadiponectinemia and hyperresistinemia alone. The AR index was more strongly correlated with the insulin resistance indexes and key metabolic endpoints of T2DM and MS than adiponectin and resistin levels alone. The AR index was also correlated with a higher number of MS components than adiponectin and resistin levels alone. The IR_ARindex was formulated as log₁₀(I₀G₀)+log₁₀(I₀G₀)log₁₀(R₀/A₀). The normal reference range of the IR_ARindex for insulin sensitive individuals was between 3.265 and 3.538. The minimum cut-off values of the IR_ARindex for insulin resistance assessment were between 3.538 and 3.955.</p> <p>Conclusions</p> <p>The novel AR and IR_ARindexes are cost-effective, precise, reproducible and reliable integrated diagnostic biomarkers of insulin sensitivity for screening subjects with increased risk of future development of T2DM and MS.</p

Nε-(Carboxymethyl)lysine and Coronary Atherosclerosis-Associated Low Density Lipoprotein Abnormalities in Type 2 Diabetes: Current Status

In comparison to the general population, individuals with diabetes suffer a 3- to 4-fold increased risk for developing complications of atherosclerosis and vascular insufficiency. This fact should be taken into account to develop a suitable determinant for the early detection of these complications and subsequently reduce the adverse effect of type 2 diabetes. In vitro experiments have shown that the products of glucose auto-oxidation and Amadori adducts are both potential sources of Nε-(carboxymethyl)lysine (CML). Excessive formation of CML on low density lipoprotein (LDL) has been proposed to be an important mechanism for the dyslipidemia and accelerated atherogenesis observed in patients with type 2 diabetes. It has been postulated that the uptake of CML-LDL by LDL receptors is impaired, thereby decreasing its clearance from the blood circulation. Alternatively, the uptake of these modified LDL particles by scavenger receptors on macrophages and vascular smooth muscle cells (SMCs) and by AGE receptors on endothelial cells, SMCs, and monocytes is highly enhanced and this, in turn, is centrally positioned to contribute to the pathogenesis of diabetic vascular complications especially coronary artery disease. The present review summarizes the up-to-date information on effects and mechanism of type 2 diabetes-associated coronary atherosclerosis induced by CML-LDL modification

Role of Nε-(Carboxymethyl)Lysine in the Development of Ischemic Heart Disease in Type 2 Diabetes Mellitus

This study aims to determine the levels of Nε-(carboxymethyl)lysine (CML) in patients with Type 2 diabetic patients with and without ischemic heart disease (IHD) and to find for a possible association between circulating CML and a number of clinical parameters including lipids, hemoglobin A1c (HbA1c) and malondialdehyde (MDA) in Type 2 diabetic IHD patients. Serum CML levels were measured by enzyme-linked immunosorbent assay using polyclonal anti-CML antibodies. Serum levels of CML and MDA were assessed in 60 IHD patients with Type 2 diabetes, 43 IHD patients without Type 2 diabetes, 64 Type 2 diabetics without IHD, and 80 sex- and age-matched healthy subjects. Correlations studies between CML levels and lipids, HbA1c, and lipid peroxidation were performed in Type 2 diabetes patients with and without IHD. A statistical significance was observed in the levels of serum glucose, lipids (triglyceride, total cholesterol, HDL-cholesterol), MDA, HbA1c, CML and LDL-cholesterol (p<0.05) between the groups of the study. CML levels were significantly increased in diabetic IHD patients compared with Type 2 diabetes patients but without IHD (537.1 ± 86.1 vs 449.7 ± 54.9, p<0.001). A positive correlation was observed between serum levels of CML and MDA, r = 0.338 (p = 0.008) in Type 2 diabetes patients with IHD. However, age, HbA1c and lipids had no significant influence on CML levels among diabetics (p>0.05). In conclusion, this study demonstrates the effect of both diabetes and oxidative stress on the higher levels of circulating CML. These results showed that increased serum levels of CML are associated with the development of IHD in Type 2 diabetes mellitus

F2-Isoprostanes as Novel Biomarkers for Type 2 Diabetes: a Review

Oxidative stress (OS) has been implicated as one of the major underlying mechanisms behind many acute and chronic diseases. However, the measurement of free radicals or their end products is complicated. Isoprostanes, derived from the non-enzymatic peroxidation of arachidonic acid are now considered to be reliable biomarkers of oxidant stress in the human body. Isoprostanes are involved in many of the human diseases such as type 2 diabetes. In type 2 diabetes elevated levels of F2-Isoprostanes (F2-IsoPs) have been observed. The measurement of bioactive F2-IsoPs levels offers a unique noninvasive analytical tool to study the role of free radicals in physiology, oxidative stress-related diseases, and acute or chronic inflammatory conditions. Measurement of oxidative stress by various other methods lacks specificity and sensitivity. This review aims to shed light on the implemention of F2-IsoPs measurement as a gold-standard biomarker of oxidative stress in type 2 diabetics

Genistein-induced fluid accumulation in ovariectomised rats' uteri is associated with increased cystic fibrosis transmembrane regulator expression

OBJECTIVE: High genistein doses have been reported to induce fluid accumulation in the uteri of ovariectomised rats, although the mechanism underlying this effect remains unknown. Because genistein binds to the oestrogen receptor and the cystic fibrosis transmembrane regulator mediates uterine fluid secretion, we hypothesised that this genistein effect involves both the oestrogen receptor and cystic fibrosis transmembrane regulator. METHODS: Ovariectomised adult female Sprague-Dawley rats were treated with 25, 50, or 100 mg/kg/day genistein for three consecutive days with and without the ER antagonist ICI 182780. One day after the final drug injection, the animals were humanely sacrificed, and the uteri were removed for histology and cystic fibrosis transmembrane regulator mRNA and protein expression analysis using real-time polymerase chain reaction and Western blotting, respectively. The cystic fibrosis transmembrane regulator protein distribution was analysed visually by immunohistochemistry. RESULTS: The histological analysis revealed an increase in the circumference of the uterine lumen with increasing doses of genistein, which was suggestive of fluid accumulation. Moreover, genistein stimulated a dose-dependent increase in the expression of cystic fibrosis transmembrane regulator protein and mRNA, and high-intensity cystic fibrosis transmembrane regulator immunostaining was observed at the apical membrane of the luminal epithelium following 50 and 100 mg/kg/day genistein treatment. The genistein-induced increase in uterine luminal circumference and cystic fibrosis transmembrane regulator expression was antagonised by treatment with ICI 182780. CONCLUSION: Genistein-induced luminal fluid accumulation in ovariectomised rats' uteri involves the oestrogen receptor and up-regulation of cystic fibrosis transmembrane regulator expression, and these findings reveal the mechanism underlying the effect of this compound on changes in fluid volume in the uterus after menopause

Pregnancy-Induced Hypertension and Preeclampsia: Levels of Angiogenic Factors in Malaysian Women

Preeclampsia (PE) is a major contributor to maternal and fetal mortality. The cause of preeclampsia remains unclear, but oxidative stress on the endothelium leading to endothelial dysfunction is said to be the root cause of the disease. The aim of this study was to measure and determine the plasma levels of key angiogenic factors in pregnancy as an indicator for the early onset of preeclampsia in pregnancy. Plasma levels of circulating a soluble fms like tyrosine kinase-1 (sFlt-1), an anti-angiogenic factor, vascular endothelial growth factor (VEGF) and placental growth factor (PIGF), both pro-angiogenic factors were analyzed in normal pregnant Malaysian women (control group, n = 34), women with pregnant induced hypertension (PIH, n = 34) and women with preeclampsia (PE, n = 34) all at three gestational ages, 24–28 weeks (early pregnancy: EP), 32–36 weeks (late pregnancy: LP) and 6 weeks after delivery (postpartum: PN). The plasma levels of angiogenic factors were determined by ELISA. sFlt-1 levels were elevated in PIH and PE patients as compared to controls. PIGF and VEGF were significantly decreased in PIH and PE as compared to the controls. These results suggest that elevated concentration of sFlt-1 and suppressed levels of PIGF and VEGF may contribute to the development of hypertension in pregnancy which precedes preeclampsia

The Occurrence of Pangasius polyuranodon Bleeker, 1852 (Teleostei: Pangasiidae) in Peninsular Malaysia with Remarks on the Comparative Morphology with Pseudolais micronemus (Bleeker, 1847)

This paper presents the first reliable record on the occurrence of the pangasiid catfish, Pangasius polyuranodon, in Peninsular Malaysia. It was previously unnoticed because of misidentification due to its close morphological appearance to Pseudolais micronemus. Pangasius polyuranodon can be positively distinguished from P. micronemus with a combination of characters: Distinctive palatal dentition with a large nearly squared vomerine tooth patch with small lateral palatine toothplates; longer maxillary and mandibular barbels; higher count of anal fin rays; higher counts of gill rakers on the first gill arch. Other characters are: longer caudal peduncle 19.84 ± 24.27% vs 18.35 ± 1.57% standard length (SL); wider anterior snout 35.49-40.60% head length (HL) and wider mouth 45.15-59.65% HL. This finding has important implications for taxonomy and conservation of indigenous Pangasiid catfishes, due to its close morphological appearance to the more abundant P. micronemus but with different biology and ecological behavior, thus necessitating different management and conservation strategies

Association of plasminogen activator inhibitor-1 and tissue plasminogen activator with type 2 diabetes and metabolic syndrome in Malaysian subjects

<p>Abstract</p> <p>Background</p> <p>Increased plasma plasminogen activator inhibitor-1 (PAI-1) activity and decreased tissue plasminogen activator (tPA) activity could be considered a true component of the metabolic syndrome (MetS) associated with an increased risk of developing cardiovascular diseases (CVD) and fibrinolytic abnormalities. The aim of this study was to investigate the association of tPA and its inhibitor PAI-1 with type 2 diabetes (T2D) and MetS and interrelationship between PAI-1and tPA activities and antigens in Malaysian T2D and normal subjects.</p> <p>Methods</p> <p>The plasma activities and antigens of PAI-1 and tPA and the levels of the tPA/PAI-1 complex as well as serum insulin, parameter of the coronary risk panel and plasma glucose at fasting state were studied in 303 T2D subjects (227 with MetS and 76 without MetS), 131 normal non-diabetic non-metabolic subjects and 101 non-diabetic MetS subjects.</p> <p>Results</p> <p>The PAI-1 activity was higher in subjects with T2D with MetS (P = 9.8 × 10^-19) and non-diabetic subjects with MetS (P = 3.0 × 10^-15), whereas the tPA activity was lower in T2D with MetS (P = 0.003) as compare to normal subjects. Plasma tPA antigen levels were higher in subjects with T2D with MetS (P = 8.9 × 10^-24), T2D without MetS (P = 1.3 × 10^-13) and non-diabetic MetS subjects (P = 0.002). The activity and antigen of PAI-1 in normal subjects were related to insulin resistance (P = 2.2 × 10^-4; 0.007). Additionally, the PAI-1 activity was associated with an increased waist circumference (P = 2.2 × 10^-4) and decreased HDL-c (P = 0.005), whereas the tPA activity was associated with decreased FBG (P = 0.028). The highest correlation was between PAI-1 activity and its antigen (R²= 0.695, P = 1.1 × 10^-36) in diabetic subjects. The tPA activity negatively correlated with its antigen (R²= -0.444, P = 7.7 × 10^-13) in normal subjects and with the PAI-1 activity and antigen (R²= -0.319, P = 9.9 × 10^-12; R2 = -0.228, P = 3.4 × 10^-6) in diabetic subjects.</p> <p>Conclusions</p> <p>PAI-1 and tPA activities and antigens were associated with diabetes and MetS parameters in Malaysian subjects.</p