Studies on the glycemic and lipidemic effect of Murraya koenigii in experimental animals

Diabetes is often accompanied by lipid abnormalities, which contribute significantly to cardiovascular morbidity and mortality in diabetic patients. Previously, we have demonstrated potent hypoglycemic activity of lyophilized aqueous extract of Murraya koenigii leaves in normal and alloxan induced diabetic rabbits for short duration of 6 h. In this study, we examined the effect of 1 month oral administration of Murraya koenigii aqueous leaves extract in normal and STZ induced severe diabetic rats, at the dose of 300 mg/kg bw, on various biochemical parameters, viz., fasting blood glucose (FBG), total cholesterol (TC), HDL-cholesterol (HDL), triglyceride (TG), alkaline phosphatase (ALKP), serum glutamate oxaloacetate and pyruvate transaminases (SGOT and SGPT) and serum creatinine. In case of diabetic animals fasting blood glucose (FBG) levels of treated animals reduced by 48.2% after 30 days treatment with the aqueous leaves extract. A fall of 19.2 and 30.8% in TC and 22.97 and 37.1% in TG levels were also observed in the case of treated normal as well as diabetic rats, respectively. Feeding the extract increased the HDL-cholesterol level by 16 and 29.4% in normal and diabetic rats, respectively, as compared with their initial values. In the normal rats after 1 month of oral administration of the extract SGOT and SGPT levels were decreased by 21.7 and 25.0%. Serum alkaline phosphatase values of the treated normal animals were also reduced by 33% while negligible change was observed in the normal control animals. In the case of diabetic rats, SGOT and SGPT levels were reduced by 36.7 and 32.2%, respectively, whereas ALKP levels decreased by 39.7% after 1 month oral administration of the extract. The serum creatinine levels decrease in normal as well as in the diabetic animals by 17.75 and 18.2%, respectively, as compared to initial values. In the diabetic control animals the urinary sugar remains at +4 level but there was a decrease of 75% in urine sugar in the case of treated diabetic rats. This indicates that the aqueous extract of Murraya koenigii has favorable effect in bringing down the severity of diabetes.     

The apolipoprotein C-II variant apoC-IILys19→Thr is not associated with dyslipidemia in an affected kindred

The rare apolipoprotein C-II (apoC-II) mutation, apoC-II_Lys19→Thr, also known as apoC-II-v, has been found previously in association with hyperlipoproteinemia. From a lipid clinic screening we identified three unrelated individuals who had the apoC-II_Lys19→Thr mutation. Among eight family members of one proband, we have found another four who were affected. None of the inviduals in this kindred is dyslipidemic and there is no difference in lipid levels between affected and unaffected family members. Therefore, we conclude that the presence of this apolipoprotein variant by itself has no effect on lipoprotein levels. In addition, the apolipoprotein E (apoE) isoform, apoE4 does not have a synergistic effect on lipoprotein levels in this kindred, in contrast to observations on the interaction of apoE4 with another apoC-II mutant (apoC-II_Toronto). The single nucleotide substitution that causes the apoC-II_Lys19→Thr variant introduces a previously unrecognized restriction site (for Mae III), that provides for easy screening.     

Acute effects of fructose consumption on uric acid and plasma lipids in patients with impaired renal function

Objective

Metabolic disturbances are common in patients with renal function impairment and are related to high rates of cardiovascular incidents and mortality. Kidney transplantation leads to improved survival but may lead to additional metabolic alterations caused by immunosuppressive drugs and improved nutrition.

Materials and methods

The short-term effect of oral fructose load on serum uric acid (UA), plasma lipids, and blood pressure (BP) was studied in 85 patients with chronic kidney disease (CKD) and impairment of renal function (glomerular filtration rate 50–65 ml/min per 1.73 m²), comprising 55 renal transplant recipients (RTR) treated with standard triple immunosuppressive therapy including a calcineurin inhibitor (CNI) cyclosporine A (CsA) or tacrolimus (Tac) and 30 non-transplanted patients with CKD. Both non-transplanted CKD patients and RTR had stable renal function and a comparable degree of kidney dysfunction. All subjects received orally 70 g of fructose dissolved in 200 ml of water. Serum UA, lipids, and blood pressure were measured at baseline and 60, 120, 180, and 240 minutes after fructose administration.

Results

There was a significant increase of serum UA concentration (p < 0.001) in both CKD patients and RTR – CsA- or Tac-treated patients comparable in the latter. Total cholesterol (TC), LDL, and HDL cholesterol significantly decreased and serum triglycerides (TG) markedly increased in RTR, whereas in CKD patients all serum lipid fractions increased. Blood pressure was unaffected by fructose intake.

Conclusion

Both non-transplanted and transplanted patients with mild renal function impairment show similar acute purine metabolic disturbances following oral administration of fructose but in the latter dietary fructose may induce a smaller hyperlipidemic response.     

Formaldehyde alters triglyceride synthesis and very low-density lipoprotein secretion in a time-dependent manner

Formaldehyde is a common indoor air pollutant that is toxic to the liver. This study aimed to investigate the effects of formaldehyde on triglyceride metabolism in human hepatocellular carcinoma cells (HepG2). Cell viability was detected using a MTT (3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide) assay. Following treatment with different concentrations of formaldehyde for 24 and 48 h, the intra and extra-hepatocellular triglyceride (TG) content was determined using a chemical-enzymatic method; Western blotting was used to detect the levels of fatty acid synthesis and VLDL-related proteins. Our results showed that cell viability significantly decreased after formaldehyde treatment (0.5–12.5 mM, 24/48 h). Extracellular TG levels in the hepatocytes increased after formaldehyde treatment at 0.004 mM–0.1 mM for 24 h. SREBP-1c, ACC, FASN, and MTP, CES3 and DGAT1 proteins increased significantly after 24 h of formaldehyde treatment. Intracellular TG levels decreased for 48 h treatment of formaldehyde. AMPKα increased significantly in all tested groups and p-AMPK increased significantly after 0.1 mM formaldehyde treatment for 48 h. Our results indicated that short–term formaldehyde exposure balances triglyceride metabolism by promoting hepatocellular TG synthesis and VLDL secretion; Long-term formaldehyde disturbs the TG metabolism balance in the hepatocytes.     

Oxidatively Modified Very Low Density Lipoprotein Enhances Monocyte Adhesion to Endothelial Cells

ＯｘｉｄａｔｉｖｌｙＭｏｄｉｆｉｅｄＶｅｒｙＬｏｗＤｅｎｓｉｔｙＬｉｐｏｐｒｏｔｅｉｎＥｎｈａｎｃｅｓＭｏｎｏｃｙｔｅＡｄｈｅｓｉｏｎｔｏＥｎｄｏｔｈｅｌｉａｌＣｅｌｌｓＦＥＮＧＹｏｕ－ｍｅｉ（冯友梅）；ＺＨＡＮＧＺｈｉ－ｂｉｎｇ（张志兵）；ＷＡＮＧ...     

Alterations of lipids and apolipoprotein CIII in very low density lipoprotein subspecies in type 2 diabetes

Aims/hypothesis Very low density lipoprotein (VLDL) particles are heterogeneous, comprising two main subspecies, VLDL 1 (Sf 60-400) and VLDL 2 (Sf 20-60). The aim of the study was to examine the distribution and composition of VLDL subspecies in type 2 diabetes.Subjects, materials and methods We studied the composition and concentration of triglyceride-rich lipoproteins (TRLs) in 217 type 2 diabetic patients and 93 control subjects between 50 and 75 years of age. Lipoprotein subspecies were separated by density-gradient ultracentrifugation. Apolipoprotein (apo) CIII and apo E in plasma and apo CIII in TRL subspecies were measured by nephelometry and apo CII in serum by a commercial kit using a single radial immunodiffusion method.Results The concentrations of VLDL 1, VLDL 2 and intermediate density lipoprotein were significantly increased in type 2 diabetes subjects, the change being most marked for VLDL 1. There was a strong linear correlation between VLDL 1 triglycerides and plasma triglycerides in both groups (r=0.879, p<0.001 and r=0.899, p<0.001). Diabetic subjects had markedly higher plasma ratios of apo CII:apo CIII and apo CIII:apo E. Despite elevated plasma apo CIII, type 2 diabetic subjects had a relative deficiency of apo CIII in all TRL subspecies, suggesting profound disturbances of apo CIII metabolism.Conclusions/interpretation The elevation of VLDL 1 triglycerides is the major determinant of plasma triglyceride concentration in normal subjects and in type 2 diabetic individuals. Both apo CIII and apo E metabolism are disturbed in type 2 diabetes.     

Glycation of very low density lipoprotein from rat plasma impairs its catabolism

Summary Rat VLDL were glycated in vitro in the presence or absence of a reducing agent. Prior to glycation, the VLDL triglyceride was endogenously radiolabelled with [³H]-oleic acid. Post glycation the VLDL B-apoprotein was exogenously radiolabelled with [¹³¹]I. The double labelled VLDL was then injected into normal rats and the decline in plasma radioactivity of the two isotopes was used as a measure of triglyceride and particle clearance. VLDL glycated in either the presence or absence of reducing agent exhibited a significantly slower removal of triglyceride and apoprotein B compared to normal VLDL. The ability of glycated VLDL triglyceride to act as substrate for lipoprotein lipase and hepatic lipase was examined. Increasing concentrations of normal and glycated VLDL triglyceride were incubated with post-heparin plasma. The kinetics of triglyceride hydrolysis were determined in a manner analagous to Michaelis-Menten analysis. Glycated VLDL was found to be poorer than normal VLDL as a substrate for lipoprotein lipase. Glycation of VLDL appears to interfere with the lipolysis of its triglyceride. This may explain the delayed clearance of glycated VLDL triglyceride in vivo. Glycation also extended the mean plasma residence time of the VLDL particle. These factors may, in part, contribute to the hypertriglyceridaemia observed in subjects with diabetes mellitus.     

Plasma lipoproteins and apolipoproteins in insulin-dependent and young non-insulin-dependent Arab women

Summary Plasma lipids, lipoproteins and apolipoproteins (apo) were analysed in 30 young Arab IDDM and 50 young insulin-requiring NIDDM women. The mean age of IDDM and NIDDM groups was 20.2 and 34.5 years, and mean duration of diabetes was 5.7 and 4.6 years, respectively. Two groups of 40 and 60 healthy women (matched for age and BMI) provided corresponding control groups. In comparison with control subjects, diabetics showed marked increases in the following parameters: total cholesterol (TC), low density lipoprotein (LDL) cholesterol, total triglycerides (TG), very low density lipoprotein (VLDL) triglycerides, phospholipids, apoB, LDL apoB, glucose and glycosylated hemoglobin (HbA_1c) as well as the ratios of total cholesterol/high density lipoprotein (HDL) cholesterol, LDL-cholesterol/HDL-cholesterol, LDL cholesterol/high density lipoprotein 2 (HDL₂) cholesterol and apoB/apoAI. Plasma LCAT activity, concentrations of HDL₃ apoAI and apoAII in plasma and lipoprotein fractions were normal in both the diabetic groups. Levels of C-peptide, HDL, HDL₂ and HDL₃ cholesterol, plasma apoAI, HDL apoAI and HDL₂ apoAI were markedly decreased in the diabetic groups as compared to their corresponding controls. There was no significant correlation between fasting glucose or HbA_1c and any of the above parameters. Despite insulin therapy in both the diabetic groups studied, abnormalities in lipids, apoB and apoAI still persisted. Our data suggest a possible higher risk of atherosclerosis in these patients.