Mohamad Abu Bakar

Mitochondrial dysfunction as a central event for mechanisms underlying insulin resistance: the roles of long chain fatty acids

Insulin resistance is characterized by hyperglycaemia, dyslipidaemia and oxidative stress prior to the development of type 2 diabetes mellitus. To date, a number of mechanisms have been proposed to link these syndromes together, but it remains unclear what the unifying condition that triggered these events in the progression of this metabolic disease. There have been a steady accumulation of data in numerous experimental studies showing the strong correlations between mitochondrial dysfunction, oxidative stress and insulin resistance. In addition, a growing number of studies suggest that the raised plasma free fatty acid level induced insulin resistance with the significant alteration of oxidative metabolism in various target tissues such as skeletal muscle, liver and adipose tissue. In this review, we herein propose the idea of long chain fatty acid‐induced mitochondrial dysfunctions as one of the key events in the pathophysiological development of insulin resistance and type 2 diabetes. The accumulation of reactive oxygen species, lipotoxicity, inflammation‐induced endoplasmic reticulum stress and alterations of mitochondrial gene subset expressions are the most detrimental that lead to the developments of aberrant intracellular insulin signalling activity in a number of peripheral tissues, thereby leading to insulin resistance and type 2 diabetes. Copyright

Mitochondrial dysfunction as a central event for mechanisms underlying insulin resistance

Insulin resistance is characterized by hyperglycaemia, dyslipidaemia and oxidative stress prior to the development of type 2 diabetes mellitus. To date, a number of mechanisms have been proposed to link these syndromes together, but it remains unclear what the unifying condition that triggered these events in the progression of this metabolic disease. There have been a steady accumulation of data in numerous experimental studies showing the strong correlations between mitochondrial dysfunction, oxidative stress and insulin resistance. In addition, a growing number of studies suggest that the raised plasma free fatty acid level induced insulin resistance with the significant alteration of oxidative metabolism in various target tissues such as skeletal muscle, liver and adipose tissue. In this review, we herein propose the idea of long chain fatty acid‐induced mitochondrial dysfunctions as one of the key events in the pathophysiological development of insulin resistance and type 2 diabetes. The accumulation of reactive oxygen species, lipotoxicity, inflammation‐induced endoplasmic reticulum stress and alterations of mitochondrial gene subset expressions are the most detrimental that lead to the developments of aberrant intracellular insulin signalling activity in a number of peripheral tissues, thereby leading to insulin resistance and type 2 diabetes. Copyright

A Structural Study of Epoxidized Natural Rubber (ENR-50) and Its Cyclic Dithiocarbonate Derivative Using NMR Spectroscopy Techniques

A structural study of epoxidized natural rubber (ENR-50) and its cyclic dithiocarbonate derivative was carried out using NMR spectroscopy techniques. The overlapping 1H-NMR signals of ENR-50 at δ 1.56, 1.68–1.70, 2.06, 2.15–2.17 ppm were successfully assigned. In this work, the 13C-NMR chemical shift assignments of ENR-50 were consistent to the previously reported work. A cyclic dithiocarbonate derivative of ENR-50 was synthesized from the reaction of purified ENR-50 with carbon disulfide (CS2), in the presence of 4-dimethylaminopyridine (DMAP) as catalyst at reflux temperature. The cyclic dithiocarbonate formation involved the epoxide ring opening of the ENR-50. This was followed by insertion of the C–S moiety of CS2 at the oxygen attached to the quaternary carbon and methine carbon of epoxidized isoprene unit, respectively. The bands due to the C=S and C–O were clearly observed in the FTIR spectrum while the 1H-NMR spectrum of the derivative revealed the peak attributed to the methylene protons had split. The 13C-NMR spectrum of the derivative further indicates two new carbon peaks arising from the >C=S and quaternary carbon of cyclic dithiocarbonate. All other 1H- and 13C-NMR chemical shifts of the derivative remain unchanged with respect to the ENR-50.

Carbon Black (CB)/Rice Husk Powder (RHP) Hybrid Filler-Filled Natural Rubber Composites: Effect of CB/RHP Ratio on Property of the Composites

Carbon black (CB)/rice husk powder (RHP) hybrid filler filled natural rubber (NR) composites with various filler ratios (0/30, 5/25, 10/20, 20/10 and 30/0) were prepared. The influence of CB/RHP ratio on curing characteristics, tensile properties and fatique life of the composites was investigated. It has been found that incorporation of CB in the hybrid filler decreases the scorch time and cure time but increases maximum torque. As CB content increases, the tensile strength, modulus at 100% and 300% elongation and fatique life increase whereas the elongation at break decreases. SEM studies also reveal poor adhesion between RHP particles and NR matrix which causes inferior mechanical properties.

Modified natural rubber induced aqueous to toluene phase transfer of gold and platinum colloids

Citrate-stabilized gold and platinum particles were prepared in aqueous phase and transferred to toluene phase by employing 2-propanol as the transfer agent. It was found that the modified natural rubber (ENR) induced the phase transfer and assisted the dispersion of the citrate-free metal particles into the organic phase. The amounts of gold and platinum transferred are 93.4% and 86.1%, respectively. This phase transfer technique produced organosols of smaller particle sizes and narrower size distribution with self-assembly arrangements when compared to those prepared via the previous in situ preparations. The respective average particle size and standard deviation of gold before and after phase transfer were 6.3 ± 1.7 nm and 7.2 ± 1.3 nm, while for platinum they were 4.0 ± 0.7 nm and 4.2 ± 0.8 nm. The slight increase in the average sizes and overall size distributions in both metals after transfer was attributed to multiparticle aggregation in the organic phase.

Effect of Organo-Modified Nanoclay on the Thermal and Bulk Structural Properties of Poly(3-hydroxybutyrate)-Epoxidized Natural Rubber Blends: Formation of Multi-Components Biobased Nanohybrids

Multi-component nanohybrids comprising of organo-modified montmorillonite (MMT) and immiscible biopolymer blends of poly(3-hydroxybutyrate) (PHB) and epoxidized natural rubber (ENR-50) were prepared by solvent casting technique. The one and three dimensional morphology of PHB/ENR-50/MMT systems were studied using Polarizing Optical Microscopy (POM) and Scanning Electron Microscopy (SEM). Differential scanning calorimetry (DSC) technique was used to evaluate the thermal properties of the nanohybrids. The melting temperature (Tm) and enthalpy of melting (ΔHm) of PHB decrease with respect to the increase in ENR-50 as well as MMT content. The non-isothermal decomposition of the nanohybrids was studied using thermogravimetric (TG-DTG) analysis. FTIR-ATR spectra supported ring opening of the epoxide group via reaction with carboxyl group of PHB and amines of organic modifier. The reaction mechanism towards the formation of the nanohybrids is proposed.

Surface Characteristics and Catalytic Activity of Copper Deposited Porous Silicon Powder

Porous structured silicon or porous silicon (PS) powder was prepared by chemical etching of silicon powder in an etchant solution of HF: HNO3: H2O (1:3:5 v/v). An immersion time of 4 min was sufficient for depositing Cu metal from an aqueous solution of CuSO4 in the presence of HF. Scanning electron microscopy (SEM) analysis revealed that the Cu particles aggregated upon an increase in metal content from 3.3 wt% to 9.8 wt%. H2-temperature programmed reduction (H2-TPR) profiles reveal that re-oxidation of the Cu particles occurs after deposition. Furthermore, the profiles denote the existence of various sizes of Cu metal on the PS. The Cu-PS powders show excellent catalytic reduction on the p-nitrophenol regardless of the Cu loadings.

Amelioration of mitochondrial dysfunction-induced insulin resistance in differentiated 3T3-L1 adipocytes via inhibition of NF-κB pathways.

A growing body of evidence suggests that activation of nuclear factor kappa B (NF-κB) signaling pathways is among the inflammatory mechanism involved in the development of insulin resistance and chronic low-grade inflammation in adipose tissues derived from obese animal and human subjects. Nevertheless, little is known about the roles of NF-κB pathways in regulating mitochondrial function of the adipose tissues. In the present study, we sought to investigate the direct effects of celastrol (potent NF-κB inhibitor) upon mitochondrial dysfunction-induced insulin resistance in 3T3-L1 adipocytes. Celastrol ameliorates mitochondrial dysfunction by altering mitochondrial fusion and fission in adipocytes. The levels of oxidative DNA damage, protein carbonylation and lipid peroxidation were down-regulated. Further, the morphology and quantification of intracellular lipid droplets revealed the decrease of intracellular lipid accumulation with reduced lipolysis. Moreover, massive production of the pro-inflammatory mediators tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were markedly depleted. Insulin-stimulated glucose uptake activity was restored with the enhancement of insulin signaling pathways. This study signified that the treatments modulated towards knockdown of NF-κB transcription factor may counteract these metabolic insults exacerbated in our model of synergy between mitochondrial dysfunction and inflammation. These results demonstrate for the first time that NF-κB inhibition modulates mitochondrial dysfunction induced insulin resistance in 3T3-L1 adipocytes.

Celastrol protects against antimycin A-induced insulin resistance in human skeletal muscle cells

Mitochondrial dysfunction and inflammation are widely accepted as key hallmarks of obesity-induced skeletal muscle insulin resistance. The aim of the present study was to evaluate the functional roles of an anti-inflammatory compound, celastrol, in mitochondrial dysfunction and insulin resistance induced by antimycin A (AMA) in human skeletal muscle cells. We found that celastrol treatment improved insulin-stimulated glucose uptake activity of AMA-treated cells, apparently via PI3K/Akt pathways, with significant enhancement of mitochondrial activities. Furthermore, celastrol prevented increased levels of cellular oxidative damage where the production of several pro-inflammatory cytokines in cultures cells was greatly reduced. Celastrol significantly increased protein phosphorylation of insulin signaling cascades with amplified expression of AMPK protein and attenuated NF-κB and PKC θ activation in human skeletal muscle treated with AMA. The improvement of insulin signaling pathways by celastrol was also accompanied by augmented GLUT4 protein expression. Taken together, these results suggest that celastrol may be advocated for use as a potential therapeutic molecule to protect against mitochondrial dysfunction-induced insulin resistance in human skeletal muscle cells.

The Effect of Rice Husk Powder on Standard Malaysian Natural Rubber Grade L (SMR L) and Epoxidized Natural Rubber (ENR 50) Composites

The effects of rice husk powder (RHP) loading and two types of natural rubber matrix (SMR L and ENR 50) on curing characteristics and mechanical properties were studied. The scorch time and cure time decreased with increasing RHP loading whereas maximum torque showed an increasing trend. SMR L composites possessed longer scorch time and cure time than ENR 50 composites. Incorporation of RHP into both rubbers improved tensile modulus significantly but decreased tensile strength and elongation at break. SMR L composites exhibited the lower tensile modulus and higher tensile strength and elongation at break than ENR 50 composites.