Silybin, is one imminent therapeutic for drug induced hepatotoxicity, human prostate adenocarcinoma and other degenerative organ diseases. Recent evidences suggest that silybin influences gluconeogenesis pathways favorably and is beneficial in the treatment of type 1 and type 2 diabetes. The compound however is constrained due to solubility (0.4 mg/mL) and bioavailabilty limitations. Appropriate nanoparticle design for silybin in biocompatible polymers was thus proposed as a probable solution for therapeutic inadequacy. New surface engineered biopolymeric nanoparticles with high silybin encapsulation efficiency of 92.11% and zeta potential of +21 mV were designed. Both the pure compound and the nanoparticles were evaluated in vivo for the first time in experimental diabetic conditions. Animal health recovered substantially and the blood glucose levels came down to near normal values after 28 days treatment schedule with the engineered nanoparticles. Restoration from hyperglycemic damage condition was traced to serum insulin regeneration. Serum insulin recovered from the streptozotocin induced pancreatic damage levels of 0.17 ± 0.01 µg/lit to 0.57 ± 0.11 µg/lit after nanoparticle treatment. Significant reduction in glycated hemoglobin level, and restoration of liver glycogen content were some of the other interesting observations. Engineered silybin nanoparticle assisted recovery in diabetic conditions was reasoned due to improved silybin dissolution, passive transport in nanoscale, and restoration of antioxidant status.
The vascular endothelial growth factor (VEGF) family of cytokines are important regulators of angiogenesis that have emerged as important targets for the treatment of obesity. While serum VEGF levels rise during obesity, recent studies using genetic models provide conflicting evidence as to whether VEGF prevents or accelerates metabolic dysfunction during obesity. In the current study, we sought to identify the effects of VEGF-A neutralization on parameters of glucose metabolism and insulin action in a dietary mouse model of obesity. Within only 72 h of administration of the VEGF-A-neutralizing monoclonal antibody B.20-4.1, we observed almost complete reversal of high-fat diet-induced insulin resistance principally due to improved insulin sensitivity in the liver and in adipose tissue. These effects were independent of changes in whole-body adiposity or insulin signaling. These findings show an important and unexpected role for VEGF in liver insulin resistance, opening up a potentially novel therapeutic avenue for obesity-related metabolic disease.
New-onset diabetes mellitus after transplantation (NODAT) is one of the complications that is increasingly occurring among kidney transplanted patients. It is associated with the risk of cardiovascular disease, graft failure and mortality. The risk of NODAT development increases with time from transplantation. Therefore, early detection and prompt action are essential in reducing the risk of NODAT and its complications. This paper aims to review the screening parameters, prevention and management strategies for NODAT in both pre- and post-transplantation conditions. The pre-transplant patient should be screened for diabetes and cardiometabolic risk factors. Blood glucose evaluation for the pre-transplantation period is important for early detection of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), which are highly associated with the incidence of NODAT. Post-kidney transplant patients should have periodical blood glucose monitoring with more frequent assessment in the initial phase. As early hyperglycaemia development is a strong predictor for NODAT, prompt intervention is needed. When NODAT develops, monitoring and control of blood glucose profile, lipid profile, microalbuminuria, diabetic complications and comorbid conditions is recommended. Immunosuppressive regimen modification may be considered as suggested by the Kidney Disease: Improving Global Outcomes (KDIGO) guideline to reverse or to improve the diabetes after weighing the risk of rejection and other potential adverse effects. Strategies for modifying immunosuppressive agents include dose reduction, discontinuation, and selection of calcineurin inhibitor (CNI), anti-metabolite agents, mammalian target of rapamycin inhibitors (mTORi), belatacept and corticosteroids. Lifestyle modification and a conventional anti-diabetic approach, as in the type 2 diabetes mellitus guidelines, are also recommended in NODAT management.
Obesity and related metabolic diseases (e.g., type 2 diabetes, cardiovascular diseases, and hypertension) are the most prevailing nutrition-related issues in the world. An emerging feature of obesity is their relationship with chronic inflammation that begins in white adipose tissue and eventually becomes systemic. One potential dietary strategy to reduce glucose intolerance and inflammation is consumption of polyphenol-rich cocoa-like cocoa or their by-products. In vitro as well as in vivo data indicate that cocoa polyphenols (CPs) may exhibit antioxidant and anti-inflammatory properties. Polyphenols commonly found in cocoa have been reported to regulate lipid metabolism via inducing metabolic gene expression or activating transcription factors that regulate the expression of numerous genes, many of which play an important role in energy metabolism. Currently, several molecular targets (e.g., nuclear factor Kappa B, activated protein-1, peroxisome proliferator-activated receptors, liver X receptors, and adiponectin gene) have been identified, which may explain potential beneficial obesity-associated diseases effects of CPs. Further studies have been performed regarding the protective effects of CPs against metabolic diseases by suppressing transcription factors that antagonize lipid accumulation. Thus, polyphenols-rich cocoa products may diminish obesity-mediated metabolic diseases by multiple mechanisms, thereby attenuating chronic inflammation.
Recent reports have demonstrated that elevated plasma long pentraxin 3 (PTX3) levels are associated with cardiovascular and chronic kidney diseases. In the current study, we investigated the plasma PTX3 levels in 296 Malay subjects including the subjects with normal glucose tolerance (NGT) and type 2 diabetes (T2DM) patients with or without DN by using an enzyme-linked immune-sorbent assay. Results showed that in males, plasma PTX3 levels in T2DM patients without DN were lower than that in the subjects with NGT (2.78 versus 3.98 ng/mL; P = 0.021). Plasma PTX3 levels in T2DM patients with DN were decreased compared to the patients without DN (1.63 versus 2.78 ng/mL; P = 0.013). In females, however, no significant alteration of plasma PTX3 levels among NGT subjects and T2DM patients with and without DN was detected. Furthermore, an inverse correlation between PTX3 and body mass index was found in male subjects with NGT (P = 0.012; r = -0.390), but not in male T2DM patients, neither in all females. The current study provided the first evidence that decreased plasma PTX3 levels are associated with T2DM and DN in Malay men and also suggested that PTX3 may have different effects in DN and chronic kidney diseases.
Obese subjects had increased serum high sensitivity C-reactive protein (hs-CRP), decreased adiponectin levels, and impaired microvascular endothelial function compared to lean subjects. We investigated the relationships of serum hs-CRP, adiponectin and microvascular endothelial function with obesity indices and metabolic markers in overweight and obese female subjects. Anthropometric profile, body fat composition, biochemical analysis, serum hs-CRP and adiponectin levels, and microvascular endothelial function were measured in 91 female subjects. Microvascular endothelial function was determined using laser Doppler fluximetry and the process of iontophoresis. Mean age and body mass index (BMI) of subjects were 34.88 (7.87) years and 32.93 (4.82) kg/m(2). hs-CRP levels were positively correlated with weight, BMI, waist circumference, hip circumference, body fat and visceral fat. Adiponectin levels were positively correlated with insulin sensitivity index (HOMA-%S), and inversely correlated with waist hip ratio, triglyceride, fasting insulin and insulin resistance index (HOMA-IR). No relationship was seen between microvascular endothelial function and obesity indices, and metabolic markers. In overweight and obese female subjects, hs-CRP levels were correlated with obesity indices while adiponectin levels were inversely correlated with obesity indices and metabolic markers. No significant relationship was seen between microvascular endothelial function with obesity indices and metabolic markers including hs-CRP and adiponectin in female overweight and obese subjects.
Adipocytes are major tissues involved in glucose uptake second to skeletal muscle and act as the main adipocytokines mediator that regulates glucose uptake mechanism and cellular differentiation. The objective of this study were to examine the effect of the SDF7, which is a fraction consists of four flavonoid compounds (quercetin: p-coumaric acid: luteolin: apigenin=8: 26: 1: 3) from Scoparia dulcis Linn., on stimulating the downstream components of insulin signalling and the adipocytokines expression on different cellular fractions of 3T3-F442a adipocytes.
The antioxidant and anti-diabetic properties of the sequential extracts of Vernonia amygdalina based on the chemical composition of the most effective anti-diabetic extract were studied. Using DPPH and ABTS radical scavenging as well as FRAP assays, the extracts showed a consistent dose-dependent trend of potent antioxidant activity in the following solvents: water extract>methanol extract>chloroform extract>and petroleum ether extracts. In the oral glucose tolerance test, the chloroform extract exerted the highest response (33.3%), similar to metformin (27.2%), after 2h compared to the control (50.8%, P<0.05). After a 14-day administration in diabetic rats, the chloroform extract recorded the highest blood (23.5%) and serum (21.4%) glucose-lowering effects (P<0.05). GC-MS analysis of the chloroform extract revealed high levels of linoleic acid (4.72%), α-linolenic acid (10.8%) and phytols (12.0%), as well as other compounds.
Metabolic syndrome is a highly prevalent health problem within the adult population in developing countries. We aimed to study the association of physical activity levels and metabolic risk factors among Malay adults in Malaysia.
The prevalence of lifestyle-related chronic diseases is increasing and gene-diet interaction studies are limited among the Malaysian population. This study was conducted to evaluate the association and interaction effects of vascular endothelial growth factor receptor-2(VEGFR2) gene polymorphisms and dietary patterns on anthropometric and biochemical risk factors of chronic diseases in 179 Chinese Malaysian adults.
The prevalence of metabolic syndrome is increasing disproportionately among the different ethnicities in Asia compared to the rest of the world. This study aims to determine the differences in the prevalence of metabolic syndrome across ethnicities in Malaysia, a multi-ethnic country.
The primary aim of the current management of diabetes mellitus is to achieve and/or maintain a glycated hemoglobin level of ≤6.5%. However, recent evidence indicates that intensive treatment of hyperglycemia is characterized by increased weight gain, severe hypoglycemia and higher mortality. Besides, evidence suggests that it is difficult to achieve and/or maintain optimal glycemic control in many diabetic patients; and that the benefits of intensively-treated hyperglycemia are restricted to microvascular complications only. In view of these adverse effects and limitations of intensive treatment of hyperglycemia in preventing diabetic complications, which is linked to oxidative stress, this commentary proposes a hypothesis that "simultaneous targeting of hyperglycemia and oxidative stress" could be more effective than "intensive treatment of hyperglycemia" in the management of diabetes mellitus.
Polyhydroxyalkanoate (PHA) is a family of biopolymers produced by some bacteria and is accumulated intracellularly as carbon and energy storage material. Fifteen PHA-producing bacterial strains were identified from bacteria isolated from Antarctic soils collected around Casey Station (66°17'S, 110°32'E) and Signy Island (60°45'S, 45°36'W). Screening for PHA production was carried out by incubating the isolates in PHA production medium supplemented with 0.5% (w/v) sodium octanoate or glucose. 16S rRNA gene sequence analysis revealed that the isolated PHA-producing strains were mainly Pseudomonas spp. and a few were Janthinobacterium spp. All the isolated Pseudomonas strains were able to produce medium-chain-length (mcl) PHA using fatty acids as carbon source, while some could also produce mcl-PHA by using glucose. The Janthinobacterium strains could only utilize glucose to produce polyhydroxybutyrate (PHB). A Pseudomonas isolate, UMAB-40, accumulated PHA up to 48% cell dry mass when utilizing fatty acids as carbon source. This high accumulation occurred at between 5°C and 20°C, then decreased with increasing temperatures. Highly unsaturated mcl-PHA was produced by UMAB-40 from glucose. Such characteristics may be associated with the ability of UMAB-40 to survive in the cold.
In this study, PHA biosynthesis operon of Comamonas sp. EB172, an acid-tolerant strain, consisting of three genes encoding acetyl-CoA acetyltransferase (phaA(Co) gene, 1182 bp), acetoacetyl-CoA reductase (phaB(Co) gene, 738 bp) and PHA synthase, class I (phaC(Co) gene, 1694 bp) were identified. Sequence analysis of the phaA(Co), phaB(Co) and phaC(Co) genes revealed that they shared more than 85%, 89% and 69% identity, respectively, with orthologues from Delftia acidovorans SPH-1 and Acidovorax ebreus TPSY. The PHA biosynthesis genes (phaC(Co) and phaAB(Co)) were successfully cloned in a heterologous host, Escherichia coli JM109. E. coli JM109 transformants harbouring pGEM'-phaC(Co)AB(Re) and pGEM'-phaC(Re)AB(Co) were shown to be functionally active synthesising 33 wt.% and 17 wt.% of poly(3-hydroxybutyrate) [P(3HB)]. E. coli JM109 transformant harbouring the three genes from the acid-tolerant Comamonas sp. EB172 (phaCAB(Co)) under the control of native promoter from Cupriavidus necator, in vivo polymerised P(3HB) when fed with glucose and volatile mixed organic acids (acetic acid:propionic acid:n-butyric acid) in ration of 3:1:1, respectively. The E. coli JM109 transformant harbouring phaCAB(Co) could accumulate P(3HB) at 2g/L of propionic acid. P(3HB) contents of 40.9% and 43.6% were achieved by using 1% of glucose and mixed organic acids, respectively.
In this randomized controlled trial we evaluated the effectiveness of medical nutritional therapy on Arab patients with Type 2 diabetes in Oman delivered by a dietitian.
The etiology of erectile dysfunction (ED) is multi-factorial. This paper examines the association between ED, testosterone deficiency syndrome (TDS) and metabolic syndrome (MS) in Malaysian men in an urban setting. One thousand and forty-six men aged ≥ 40 years from Subang Jaya, Malaysia were randomly selected from an electoral-roll list. The men completed questionnaires that included: socio-demographic data, self-reported medical problems and the International Index of erectile function (IIEF-5). Physical examination and the following biochemical tests were performed: lipid profile, fasting blood glucose (FBG) and total testosterone. The response rate was 62.8% and the mean age of men was 55.8 ± 8.4 (41-93) years. Ethnic distribution was Chinese, 48.9%; Malay, 34.5%; Indian, 14.8%. The prevalence of moderate-severe ED was 20.0%, while 16.1% of men had TDS (< 10.4 nmol/L) and 31.3% of men had MS. Indian and Malay men were significantly more likely to have ED (p = 0.001), TDS (p < 0.001) and MS (p < 0.001) than the Chinese. Multivariate regression analysis showed that elevated blood pressure, elevated FBG, low high-density lipoprotein and heart disease were predictors of ED while all MS components were independently associated with TDS. Malay and Indian men have a higher disease burden compared to Chinese men and were more likely to suffer with ED, TDS and MS. MS components were closely related to TDS and ED.
The activities of phosphoenolpyruvate carboxykinase (PEPCK) are influenced by active glucocorticoids which are activated by 11-β-hydroxysteroid dehydrogenase 1 (11β-HSD1) while hexose-6-phosphate dehydrogenase (H6PDH) influences the activities of 11-βHSD1 in a cofactor manner. Dysregulation of PEPCK and H6PDH has been associated with the pathogenesis of metabolic syndrome. Sixteen male Sprague Dawley rats, fed ad libitum, were assigned to two groups, control and treated, with the treated group being given GA at 100mg/kg for one week. Blood and subcutaneous and visceral adipose tissue, abdominal and quadriceps femoris muscle, liver and kidney were examined. GA treatment led to an overall significant decrease in blood glucose while HOMA-IR. PEPCK activities decreased in the liver but increased in the visceral adipose tissue. H6PDH activities also decreased significantly in the liver while 11β-HSD1 activities decreased significantly in all studied tissues except for subcutaneous adipose tissue. Adipocytes in the subcutaneous and visceral depots showed a reduction in size. Though increased glycogen storage was seen in the liver, no changes were observed in the kidneys and muscles. Results from this study may imply that GA could counteract the development of type 2 diabetes mellitus by improving insulin sensitivity and probably by reduction of H6PDH, 11β-HSD1 and a selective decrease in PEPCK activities.
Reduced arterial compliance in patients with diabetes mellitus has been shown in several studies, but it has not been significantly associated with either atherosclerosis or vessel wall thickness. Blood pressure variability is still poorly explored in diabetic patients. The aim of this study was to compare blood pressure variability and arterial compliance in patients with type 2 diabetes mellitus and controls matched for sex, age, and weight. Arterial compliance was measured and noninvasive 24-h ambulatory blood pressure monitoring was performed in 18 diabetic patients and 18 controls. There was significantly higher 24-h systolic blood pressure variability (17.7 +/- 6.8 vs. 14.6 +/- 2.6 mm Hg), diastolic blood pressure variability (15.6 +/- 7.1 vs. 11.4 +/- 3.1 mm Hg), and mean arterial blood pressure variability (14.8 +/- 7.0 vs. 11.1 +/- 2.9) in diabetic patients. Systolic, diastolic, and mean arterial blood pressure variability was significantly higher during daytime but not night time in diabetic patients compared to controls. Diabetic patients also had significantly reduced small artery compliance, but no differences in large artery compliance, cardiac output, or systemic vascular resistance. The findings suggest that hyperglycemia may affect the compliance of the vascular system, resulting in high blood pressure fluctuations.
Insulin stimulates glucose uptake and promotes the translocation of glucose transporter 4 (Glut 4) to the plasma membrane on L6 myotubes. The aim of this study is to investigate affect of Scoparia dulcis Linn water extracts on glucose uptake activity and the Glut 4 translocation components (i.e., IRS-1, PI 3-kinase, PKB/Akt2, PKC and TC 10) in L6 myotubes compared to insulin.