Displaying publications 1 - 20 of 38 in total

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  1. Elnaem MH, Mohamed MHN, Huri HZ, Shah ASM
    Ther Clin Risk Manag, 2019;15:137-145.
    PMID: 30705590 DOI: 10.2147/TCRM.S182716
    Background: Cardiovascular diseases (CVDs) are the main complication leading to morbidity and mortality among patients with type 2 diabetes mellitus (T2DM). There is a large amount of evidence to support the use of lipid-lowering therapy (LLT) for the prevention of CVD. This study aimed to assess the effectiveness and prescription quality of LLT among T2DM patients and to identify its associated factors.

    Methods: A multicenter cross-sectional study included 816 T2DM patients from four different primary care centers in Pahang, Malaysia. We involved LLT-eligible T2DM patients as per the national clinical practice guidelines (CPG). The assessment of therapy effectiveness focused on the attainment of target lipid measures stated in the CPG. Evaluation of the prescription quality was classified into appropriate, potentially inappropriate, and inappropriate, based on the compliance with guidelines and existence of potential safety concerns. Binomial logistic regression was employed to identify the predictors of LLT effectiveness and prescription quality.

    Results: The overall percentage of T2DM patients receiving statin therapy was 87.6% (715/816). Statin therapy was appropriately prescribed in 71.5% of the cases. About 17.5% of the LLT prescriptions have at least one significant drug interaction with co-prescribed medications. The achievement of the primary target of low-density lipoprotein cholesterol (LDL-C) levels was observed in only 37% of T2DM patients. The LLT indication and appropriateness of prescription were significantly associated with the attainment of LDL-C treatment goals. Primary prevention, Malay race, and hypertension were identified as predictors for appropriate prescribing of LLT among T2DM subjects.

    Conclusion: There is a need to enhance the quality of LLT prescribing in the primary care setting to cover all eligible high-risk patients and ensure patient safety. Strategies to improve the achievement of LDL-C goals among patients with T2DM, such as investigating the potential role of the combination therapy and high-intensity statin therapy, are required.
  2. Huri HZ, Ling CF, Razack AH
    Ther Clin Risk Manag, 2017;13:407-419.
    PMID: 28408836 DOI: 10.2147/TCRM.S118010
    This study was conducted in a tertiary medical center in Kuala Lumpur, Malaysia. A total of 200 erectile dysfunction (ED) patients with 499 cases who had received pharmacological treatments for their ED participated in this study. Types, causes and factors associated with drug-related problems (DRPs) in ED patients with multiple comorbidities were assessed. A total of 244 DRPs with an average of 1.2±2.1 DRPs per patient were identified. Drug interaction contributed the most to DRPs occurrence. There was a significant higher risk of DRPs in patients with benign prostatic hyperplasia, lower urinary tract infection and elderly and end-stage renal disease. Early identification of types of DRPs and factors associated may enhance their prevention and management.
  3. Loganadan NK, Huri HZ, Vethakkan SR, Hussein Z
    Pharmacogenomics J, 2016 06;16(3):209-19.
    PMID: 26810132 DOI: 10.1038/tpj.2015.95
    The clinical response to sulphonylurea, an oral antidiabetic agent often used in combination with metformin to control blood glucose in type 2 diabetes (T2DM) patients, has been widely associated with a number of gene polymorphisms, particularly those involved in insulin release. We have reviewed the genetic markers of CYP2C9, ABCC8, KCNJ11, TCF7L2 (transcription factor 7-like 2), IRS-1 (insulin receptor substrate-1), CDKAL1, CDKN2A/2B, KCNQ1 and NOS1AP (nitric oxide synthase 1 adaptor protein) genes that predict treatment outcomes of sulphonylurea therapy. A convincing pattern for poor sulphonylurea response was observed in Caucasian T2DM patients with rs7903146 and rs1801278 polymorphisms of the TCF7L2 and IRS-1 genes, respectively. However, limitations in evaluating the available studies including dissimilarities in study design, definitions of clinical end points, sample sizes and types and doses of sulphonylureas used as well as ethnic variability make the clinical applications challenging. Future studies need to address these limitations to develop personalized sulphonylurea medicine for T2DM management.
  4. Ali M, Wahab IBA, Huri HZ, Yusoff MS
    Syst Rev, 2024 Apr 02;13(1):99.
    PMID: 38566190 DOI: 10.1186/s13643-024-02478-4
    BACKGROUND: Personalised learning, an educational approach that tailors teaching and learning to individual needs and preferences, has gained attention in recent years, particularly in higher education. Advances in educational technology have facilitated the implementation of personalised learning in various contexts. Despite its potential benefits, the literature on personalised learning in health sciences higher education remains scattered and heterogeneous. This scoping review aims to identify and map the current literature on personalised learning in health sciences higher education and its definition, implementation strategies, benefits, and limitations.

    METHODS: A comprehensive search of electronic databases, PubMed, Scopus, Google Scholar, Educational Research Complete, and Journal Storage (JSTOR), will be conducted to identify relevant articles. The search will be limited to articles published in the English language between 2000 and 2023. The search strategy will be designed and adapted for each database using a combination of keywords and subject headings related to personalised learning and health sciences higher education. Eligibility criteria will be applied to screen and select articles. Data extraction and quality assessment will be performed, and thematic synthesis will be used to analyse the extracted data.

    DISCUSSION: The results of the scoping review will present a comprehensive and coherent overview of the literature on personalised learning in health sciences higher education. Key themes and topics related to personalised learning, its definitions, models, implementation strategies, benefits, and limitations, will be identified. The geographical and temporal distribution of research on personalised learning in health sciences higher education will also be described. This scoping review will provide a structured synthesis of the available evidence on personalised learning in health sciences higher education, highlighting potential gaps and areas for future research. The findings will contribute to ongoing scholarly and policy debates on personalised learning in higher education, informing the development of best practices, guidelines, and future research agendas.

  5. Ahmed RH, Huri HZ, Al-Hamodi Z, Salem SD, Muniandy S
    PLoS One, 2015;10(10):e0140618.
    PMID: 26474470 DOI: 10.1371/journal.pone.0140618
    BACKGROUND: A soluble form of CD26/dipeptidyl peptidase-IV (sCD26/DPP-IV) induces DPP-IV enzymatic activity that degrades incretin. We investigated fasting serum levels of sCD26/DPP-IV and active glucagon-like peptide-1 (GLP-1) in Malaysian patients with type 2 diabetes mellitus (T2DM) with and without metabolic syndrome (MetS), as well as the associations between sCD26/DPP-IV levels, MetS, and antidiabetic therapy.

    METHODS: We assessed sCD26/DPP-IV levels, active GLP-1 levels, body mass index (BMI), glucose, insulin, A1c, glucose homeostasis indices, and lipid profiles in 549 Malaysian subjects (including 257 T2DM patients with MetS, 57 T2DM patients without MetS, 71 non-diabetics with MetS, and 164 control subjects without diabetes or metabolic syndrome).

    RESULTS: Fasting serum levels of sCD26/DPP-IV were significantly higher in T2DM patients with and without MetS than in normal subjects. Likewise, sCD26/DPP-IV levels were significantly higher in patients with T2DM and MetS than in non-diabetic patients with MetS. However, active GLP-1 levels were significantly lower in T2DM patients both with and without MetS than in normal subjects. In T2DM subjects, sCD26/DPP-IV levels were associated with significantly higher A1c levels, but were significantly lower in patients using monotherapy with metformin. In addition, no significant differences in sCD26/DPP-IV levels were found between diabetic subjects with and without MetS. Furthermore, sCD26/DPP-IV levels were negatively correlated with active GLP-1 levels in T2DM patients both with and without MetS. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-cholesterol (LDL-c) levels.

    CONCLUSION: Serum sCD26/DPP-IV levels increased in T2DM subjects with and without MetS. Active GLP-1 levels decreased in T2DM patients both with and without MetS. In addition, sCD26/DPP-IV levels were associated with Alc levels and negatively correlated with active GLP-1 levels. Moreover, metformin monotherapy was associated with reduced sCD26/DPP-IV levels. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-c.

  6. Abdullah BM, Zubairi SI, Huri HZ, Hairunisa N, Yousif E, Basu RC
    PLoS One, 2016;11(3):e0151603.
    PMID: 27008312 DOI: 10.1371/journal.pone.0151603
    Presently, plant oils which contain high percentage of linoleic acid 1 are perceived to be a viable alternative to mineral oil for biolubricant applications due to their biodegradability and technical properties. In order to get biodegradable lubricant, triester derivatives compounds (1-5) were synthesized and characterized. The processes involved were monoepoxidation of linoleic acid 2, oxirane ring opening 3, esterification 4 and acylation 5. The structures of the products were confirmed by FTIR, 1H and 13C-NMR and LC-MS. The results that showed lowest temperature properties were obtained for triester 5, with a pour point value (PP) of -73°C, highest onset temperature (260°C) and lowest volatility at 0.30%. Viscosity index (VI) increased for the ester's synthetic compounds (2, 3, 4, 5), while the PP decreased. This behavior is the result of the increase of the chain length of the branching agents. Triester based linoleic acid has improved properties such as low-temperature and tribological properties. These results will make it feasible for plant oil to be used for biolubricants, fuels in chain saws, transmission oil and brake fluid.
  7. Ahmed RH, Huri HZ, Al-Hamodi Z, Salem SD, Al-Absi B, Muniandy S
    PLoS One, 2016;11(4):e0154369.
    PMID: 27111895 DOI: 10.1371/journal.pone.0154369
    BACKGROUND: Genetic polymorphisms of the Dipeptidyl Peptidase 4 (DPP4) gene may play a role in the etiology of type 2 diabetes mellitus (T2DM). This study aimed to investigate the possible association of single nucleotide polymorphisms (SNPs) of the DPP4 gene in Malaysian subjects with T2DM and evaluated whether they had an effect on the serum levels of soluble dipeptidyl peptidase 4 (sDPP-IV).

    METHOD: Ten DPP4 SNPs were genotyped by TaqMan genotyping assays in 314 subjects with T2DM and 235 controls. Of these, 71 metabolic syndrome (MetS) subjects were excluded from subsequent analysis. The odds ratios (ORs) and their 95% confidence interval (CIs) were calculated using multiple logistic regression for the association between the SNPs of DPP4 and T2DM. In addition, the serum levels of sDPP-IV were investigated to evaluate the association of the SNPs of DPP4 with the sDPP-IV levels.

    RESULTS: Dominant, recessive, and additive genetic models were employed to test the association of DPP4 polymorphisms with T2DM, after adjusting for age, race, gender and BMI. The rs12617656 was associated with T2DM in Malaysian subjects in the recessive genetic model (OR = 1.98, p = 0.006), dominant model (OR = 1.95, p = 0.008), and additive model (OR = 1.63, p = 0.001). This association was more pronounced among Malaysian Indians, recessive (OR = 3.21, p = 0.019), dominant OR = 3.72, p = 0.003) and additive model (OR = 2.29, p = 0.0009). The additive genetic model showed that DPP4 rs4664443 and rs7633162 polymorphisms were associated with T2DM (OR = 1.53, p = 0.039), and (OR = 1.42, p = 0.020), respectively. In addition, the rs4664443 G>A polymorphism was associated with increased sDPP-IV levels (p = 0.042) in T2DM subjects.

    CONCLUSIONS: DPP4 polymorphisms were associated with T2DM in Malaysian subjects, and linked to variations in sDPP-IV levels. In addition, these associations were more pronounced among Malaysian Indian subjects.

  8. Elnaem MH, Nik Mohamed MH, Huri HZ
    PLoS One, 2019;14(9):e0220458.
    PMID: 31536502 DOI: 10.1371/journal.pone.0220458
    OBJECTIVE: Previous reports have highlighted the suboptimal utilization and prescription of statin therapy among patients with type 2 diabetes mellitus (T2DM) in the Malaysian clinical practice. This study aims to test the impact of a pharmacist-led academic detailing program on improving the overall statin therapy prescribing in Malaysian hospital and primary care settings.

    METHODS: As a quasi-experimental design with a control group and pre-tests., we examined 1,598 medical records of T2DM subjects in six healthcare facilities in the state of Pahang, Malaysia. In all study sites, there was a pre and post-intervention assessment of the percentage of appropriate statin therapy prescribing that complied with the clinical guidelines with no potential safety issues. The intervention was an academic detailing program offered to the health care providers in three study sites, while the other three sites served as the control group. A comparison of the overall percentage of appropriate statin therapy prescribing before and after the academic detailing was performed in all intervention and control sites.

    RESULTS: Overall, 797 medical records were examined in the pre-intervention phase, and 801 records were evaluated in the post-intervention phase. The academic detailing program was associated with a statistically significant difference in the proportion of appropriate statin therapy prescribing between the post-intervention phase compared to the pre-intervention phase (n = 246, 61.7% versus n = 188, 47.1%), p = 0.001. Whereas, the appropriate statin therapy prescribing in the control study sites experienced a modest change from 53.8% (214/398) to 56.7% (228/402), p = 0.220. The academic detailing showed significant increases in the proportions of appropriate statin therapy prescribing in both hospital and primary care settings.

    CONCLUSIONS: The academic detailing program was found to be significantly associated with a positive impact on the overall statin therapy prescribing among patients with T2DM in Malaysian hospital and primary care settings.

  9. Jamaluddin JL, Huri HZ, Vethakkan SR, Mustafa N
    Pharmacogenomics, 2014 Feb;15(2):235-49.
    PMID: 24444412 DOI: 10.2217/pgs.13.234
    In the adult pancreas, the expression of the genes PAX4, KCNQ1, TCF7L2, KCNJ11, ABCC8, MTNR1B and WFS1 are mainly restricted to β cells to maintain glucose homeostasis. We have identified these genes as the main regulators of incretin-mediated actions, and therefore they may potentially influence the response of DPP-4 inhibitors. This review represents the first detailed exploration of pancreatic β-cell genes and their variant mechanisms, which could potentially affect the response of DPP-4 inhibitors in Type 2 diabetes. We have focused on the signaling pathways of these genes to understand their roles in gastrointestinal incretin-mediated effects; and finally, we sought to associate gene mechanisms with their Type 2 diabetes risk variants to predict the responses of DPP-4 inhibitors for this disease.
  10. Jamaluddin JL, Huri HZ, Vethakkan SR
    Pharmacogenomics, 2016 06;17(8):867-81.
    PMID: 27249660 DOI: 10.2217/pgs-2016-0010
    AIM: To determine the clinical and genetic predictors of the dipeptidyl peptidase-4 (DPP-4) inhibitor treatment response in Type 2 diabetes mellitus (T2DM) patients.

    PATIENTS & METHODS: DPP4, WFS1 and KCNJ11 gene polymorphisms were genotyped in a cohort study of 662 T2DM patients treated with DPP-4 inhibitors sitagliptin, vildagliptin or linagliptin. Genotyping was performed by Applied Biosystems TaqMan SNP genotyping assay.

    RESULTS: Patients with triglyceride levels less than 1.7 mmol/l (odds ratio [OR]: 2.2.; 95% CI: 1.031-4.723), diastolic blood pressure (DBP) less than 90 mmHg (OR: 1.7; 95% CI: 1.009-2.892) and KCNJ11 rs2285676 (genotype CC) (OR: 2.0; 95% CI: 1.025-3.767) were more likely to response to DPP-4 inhibitor treatment compared with other patients, as measured by HbA1c levels.

    CONCLUSION: Triglycerides, DBP and KCNJ11 rs2285676 are predictors of the DPP-4 inhibitor treatment response in T2DM patients.

  11. Loganadan NK, Huri HZ, Vethakkan SR, Hussein Z
    Pharmacogenomics, 2020 06;21(9):587-600.
    PMID: 32468916 DOI: 10.2217/pgs-2019-0171
    Background: Due to several limitations in the study designs of sulfonylurea pharmacogenomics studies, we investigated the clinical and genetic predictors of secondary sulfonylurea failure in Type 2 diabetes patients. Materials & methods: Patients receiving the maximum sulfonylurea and metformin doses for >1 year were enrolled. Secondary sulfonylurea failure was defined as HbA1c >7.0% (>53 mmol/mol) after a 12-month follow-up. Results: By multivariate analysis, increased insulin resistance (HOMA2-IR), baseline HbA1c >7.0%, residing in eastern Peninsular Malaysia, and the CC genotype of rs757110 ABCC8 gene polymorphism were independent predictors of secondary sulfonylurea failure (p 
  12. Loganadan NK, Huri HZ, Vethakkan SR, Hussein Z
    Pharmacogenomics, 2021 11;22(16):1057-1068.
    PMID: 34665019 DOI: 10.2217/pgs-2021-0059
    Aim: This study investigated the incidence of sulfonylurea-induced hypoglycemia and its predictors in Type 2 diabetes (T2D) patients. Patients & methods: In this prospective, observational study, T2D patients on maximal sulfonylurea-metformin therapy >1 year were enrolled. Hypoglycemia was defined as having symptoms or a blood glucose level <3.9 mmol/l. Results: Of the 401 patients, 120 (29.9%) developed sulfonylurea-induced hypoglycemia during the 12-month follow-up. The ABCC8 rs757110, KCNJ11 rs5219, CDKAL1 rs7756992 and KCNQ1 rs2237892 gene polymorphisms were not associated with sulfonylurea-induced hypoglycemia (p > 0.05). Prior history of hypoglycemia admission (odds ratio = 16.44; 95% CI: 1.74-154.33, p = 0.014) independently predicted its risk. Conclusion: Sulfonylurea-treated T2D patients who experienced severe hypoglycemia are at increased risk of future hypoglycemia episodes.
  13. Huri HZ, Mat Sanusi ND, Razack AH, Mark R
    Patient Prefer Adherence, 2016;10:807-23.
    PMID: 27257374 DOI: 10.2147/PPA.S99544
    BACKGROUND: Erectile dysfunction (ED) is one of the most common health problems in men. ED can significantly affect a man's psychological well-being and overall health.

    PURPOSE: To investigate the association of psychological factors, patients' knowledge, and management among ED patients.

    PATIENTS AND METHODS: A total of 93 patients with an age range from 31 to 81 years who have undergone treatment for ED were included in this study.

    RESULTS: It was found that the feeling of blame (P=0.001), guilt (P=0.001), anger or bitterness (P=0.001), depression (P=0.001), feeling like a failure (P=0.001), and the feeling of letting down a partner during intercourse (P=0.001) were significantly associated with ED. Age was also found to be significantly associated with patients' psychological scale (P=0.004). In addition, the majority of patients in this study practice the right method of administration of ED therapy. However, no significant correlation was found between patients' knowledge of ED therapy and demographic characteristics.

    CONCLUSION: This study concluded that ED does affect psychological well-being of people. In addition, patient's knowledge about ED and its management is also crucial in ensuring that the patient achieves optimal therapeutic outcomes from ED therapy.

  14. Abousheishaa AA, Lazim NHM, Tang SL, Sulaiman AH, Huri HZ, Guan NC
    Patient Educ Couns, 2022 Jul;105(7):2466-2474.
    PMID: 34844812 DOI: 10.1016/j.pec.2021.11.007
    OBJECTIVES: This study aimed to develop and assess the effectiveness of an encounter decision aid for Malaysian patients with MDD to support treatment decision-making during the consultation.

    METHODS: The decision aid prototype was developed following a literature review and six focus groups. Alpha testing assessed its comprehensibility, acceptability, usability and desirability through user-centered cognitive interviews. Beta-testing evaluated preliminary evidence on its efficacy using the SDM Scale and PDMS. Feasibility was assessed by timing the consultation.

    RESULTS: The alpha testing demonstrated that the decision aid was patient-oriented, comprehensible, comprehensive, concise and objective with an appealing design. Beta-testing indicated that PtDA significantly increased patients satisfaction with SDM from patients' [83.32 (13.92) vs 85.76 (13.80); p 

  15. Hassanein MM, Huri HZ, Baig K, Abduelkarem AR
    Nutrients, 2023 Jan 29;15(3).
    PMID: 36771392 DOI: 10.3390/nu15030685
    Hormonal fluctuations, excessive clothing covering, sunscreen use, changes in body fat composition, a vitamin D-deficient diet, and a sedentary lifestyle can all predispose postmenopausal women to vitamin D deficiency. An effective supplementation plan requires a thorough understanding of underlying factors to achieve the desired therapeutic concentrations. The objective of this study was to conduct a systematic review of the predictors that affect vitamin D status in postmenopausal women. From inception to October 2022, we searched MEDLINE, Embase, Web of Science, Scopus, and clinical trial registries. Randomized clinical trials of postmenopausal women taking supplements of vitamin D with serum 25-hydroxyvitamin D (25(OH)D) measurement as the trial outcome were included. Two independent reviewers screened selected studies for full-text review. The final assessment covered 19 trials within 13 nations with participants aged 51 to 78. Vitamin D supplementation from dietary and pharmaceutical sources significantly increased serum 25(OH)D to optimal levels. Lower baseline serum 25(OH)D, lighter skin color, longer treatment duration, and prolonged skin exposure were all associated with a better response to vitamin D supplementation in postmenopausal women.
  16. Hassanein MM, Huri HZ, Abduelkarem AR, Baig K
    Nutrients, 2023 Aug 30;15(17).
    PMID: 37686835 DOI: 10.3390/nu15173804
    Recent years have witnessed the emergence of growing evidence concerning vitamin D's potential role in women's health, specifically in postmenopausal women. This evidence also includes its connection to various genitourinary disorders and symptoms. Numerous clinical studies have observed improvements in vulvovaginal symptoms linked to the genitourinary syndrome of menopause (GSM) with vitamin D supplementation. These studies have reported positive effects on various aspects, such as vaginal pH, dryness, sexual functioning, reduced libido, and decreased urinary tract infections. Many mechanisms underlying these pharmacological effects have since been proposed. Vitamin D receptors (VDRs) have been identified as a major contributor to its effects. It is now well known that VDRs are expressed in the superficial layers of the urogenital organs. Additionally, vitamin D plays a crucial role in supporting immune function and modulating the body's defense mechanisms. However, the characterization of these effects requires more investigation. Reviewing existing evidence regarding vitamin D's impact on postmenopausal women's vaginal, sexual, and urological health is the purpose of this article. As research in this area continues, there is a potential for vitamin D to support women's urogenital and sexual health during the menopausal transition and postmenopausal periods.
  17. Abu Bakar MH, Cheng KK, Sarmidi MR, Yaakob H, Huri HZ
    Molecules, 2015 May 07;20(5):8242-69.
    PMID: 25961164 DOI: 10.3390/molecules20058242
    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.
  18. Elnaem MH, Mohamed MHN, Huri HZ, Azarisman SM, Elkalmi RM
    J Pharm Bioallied Sci, 2017 Apr-Jun;9(2):80-87.
    PMID: 28717329 DOI: 10.4103/jpbs.JPBS_30_17
    Use of statin therapy in patients with type 2 diabetes mellitus (T2DM) has been recommended by most clinical guidelines. Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among T2DM patients. It has been proved that statins are effective for primary or secondary CVD prophylaxis. Reports have highlighted the underutilization of statins in clinical practice and the suboptimal adherence to guideline recommendations. This review article points to summarize the current evidence confirming the role of statins in T2DM patients and to provide an overview of factors that may affect statins' prescribing patterns and compliance in clinical practice. Initiatives to enhance statin therapy prescribing should recognize the comprehensive nature of the prescribing process. Attempts to assure proper statin prescribing and utilization can help in achieving better clinical outcomes of statin therapy.
  19. Bakar MH, Sarmidi MR, Kai CK, Huri HZ, Yaakob H
    Int J Mol Sci, 2014 Dec 02;15(12):22227-57.
    PMID: 25474091 DOI: 10.3390/ijms151222227
    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.
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