Displaying publications 81 - 100 of 184 in total

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  1. Abu Bakar MH, Azmi MN, Shariff KA, Tan JS
    Appl Biochem Biotechnol, 2019 May;188(1):241-259.
    PMID: 30417321 DOI: 10.1007/s12010-018-2920-2
    Withaferin A (WA), a bioactive constituent derived from Withania somnifera plant, has been shown to exhibit many qualifying properties in attenuating several metabolic diseases. The current investigation sought to elucidate the protective mechanisms of WA (1.25 mg/kg/day) on pre-existing obese mice mediated by high-fat diet (HFD) for 12 weeks. Following dietary administration of WA, significant metabolic improvements in hepatic insulin sensitivity, adipocytokines with enhanced glucose tolerance were observed. The hepatic oxidative functions of obese mice treated with WA were improved via augmented antioxidant enzyme activities. The levels of serum pro-inflammatory cytokines and hepatic mRNA expressions of toll-like receptor (TLR4), nuclear factor κB (NF-κB), tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand-receptor, and cyclooxygenase 2 (COX2) in HFD-induced obese mice were reduced. Mechanistically, WA increased hepatic mRNA expression of peroxisome proliferator-activated receptors (PPARs), cluster of differentiation 36 (CD36), fatty acid synthase (FAS), carnitine palmitoyltransferase 1 (CPT1), glucokinase (GCK), phosphofructokinase (PFK), and phosphoenolpyruvate carboxykinase (PCK1) that were associated with enhanced lipid and glucose metabolism. Taken together, these results indicate that WA exhibits protective effects against HFD-induced obesity through attenuation of hepatic inflammation, oxidative stress, and insulin resistance in mice.
    Matched MeSH terms: Insulin Resistance*
  2. Hamdan A, Haji Idrus R, Mokhtar MH
    PMID: 31817324 DOI: 10.3390/ijerph16244911
    Diabetes mellitus is one of the most prevalent metabolic disorders that affect people of all genders, ages, and races. Medicinal herbs have gained wide attention from researchers and have been considered to be a beneficial adjuvant agent to oral antidiabetic drugs because of their integrated effects. Concerning the various beneficial effects of Nigella sativa, this systematic review aims to provide comprehensive information on the effects of Nigella sativa on glucose and insulin profile status in humans. A computerized database search performed through Scopus and Medline via Ebscohost with the following set of keywords: Nigella Sativa OR black seed oil OR thymoquinone OR black cumin AND diabetes mellitus OR hyperglycemia OR blood glucose OR hemoglobin A1C had returned 875 relevant articles. A total of seven articles were retrieved for further assessment and underwent data extraction to be included in this review. Nigella sativa was shown to significantly improve laboratory parameters of hyperglycemia and diabetes control after treatment with a significant fall in fasting blood glucose, blood glucose level 2 h postprandial, glycated hemoglobin, and insulin resistance, and a rise in serum insulin. In conclusion, these findings suggested that Nigella sativa could be used as an adjuvant for oral antidiabetic drugs in diabetes control.
    Matched MeSH terms: Insulin Resistance/physiology
  3. Sampath Kumar A, Arun Maiya G, Shastry BA, Vaishali K, Maiya S, Umakanth S
    Diabetes Metab Syndr, 2018 10 10;13(1):344-348.
    PMID: 30641723 DOI: 10.1016/j.dsx.2018.10.005
    BACKGROUND: Basal Metabolic Rate (BMR) means the amount of energy utilized by body in physical and psychological resting rate, after a night sleep, awake without any previous physical activity post meal (10 h after last meal) & neutral environment. In people with type 2 diabetes mellitus (T2DM) there is an increase in BMR which is said to be associated with the level of glycaemic control. So, the objective of the study was to find out the correlation between BMR, Insulin resistance and Visceral fat in T2DM with peripheral neuropathy.

    MATERIALS & METHODS: A total of 50 participants with T2DM with peripheral neuropathy were included. Age group of 30-75 years were selected for the study. Participants with a known history of neurological disease, locomotor disability, and pregnancy were excluded from the study. Demographic details of the participants like duration of diabetes mellitus, age, Fasting Blood Glucose, Fasting Insulin, HOMA-IR, Glycated Haemoglobin (HBA1c), Neuropathy and Blood pressure values were noted. We measured Basal Metabolic Rate (BMR) by using Mifflin-St Jeor predictive equation in T2DM with peripheral neuropathy.

    RESULTS: The mean age of the participants is 60.16 ± 10.62. The mean duration of T2DM 13.44 ± 11.92. In the present study we found a statistical significant correlation between BMR and HOMA IR (r = 0.913*; p = 0.000), BMR & Fasting blood sugar (FBS) (r = 0.281*; p = 0.048), BMR and Visceral fat (VF) (r = 0.332*; p = 0.018).

    CONCLUSION: Basal metabolic rate is correlated to Homa-IR, visceral fat, fasting blood sugar and musculoskeletal mass among T2DM with peripheral neuropathy.

    Matched MeSH terms: Insulin Resistance*
  4. Asilah Za'don NH, Amirul Farhana MK, Farhanim I, Sharifah Izwan TO, Appukutty M, Salim N, et al.
    Med J Malaysia, 2019 12;74(6):461-467.
    PMID: 31929469
    INTRODUCTION: High-intensity interval training (HIIT) has been found to improve cardiometabolic health outcome as compared to moderate-intensity continuous exercise. However, there is still limited data on the benefits of HIIT on the expression of regulatory proteins that are linked to skeletal muscle metabolism and insulin sensitivity in obese adults. This study investigated the effects of HIIT intervention on expressions of peroxisome proliferatoractivated receptor-γ coactivator 1-∝ (PGC-1∝) and adiponectin receptor-1 (AdipoR1), insulin sensitivity (HOMAIR index), and body composition in overweight/obese individuals.

    METHODS: Fifty overweight/obese individuals aged 22-29 years were assigned to either no-exercise control (n=25) or HIIT (n=25) group. The HIIT group underwent a 12-week intervention, three days/week, with intensity of 65-80% of age-based maximum heart rate. Anthropometric measurements, homeostatic model of insulin resistance (HOMA-IR) and gene expression analysis were conducted at baseline and post intervention.

    RESULTS: Significant time-by-group interactions (p<0.001) were found for body weight, BMI, waist circumference and body fat percentage. The HIIT group had lower body weight (2.3%, p<0.001), BMI (2.7%, p<0.001), waist circumference (2.4%, p<0.001) and body fat percentage (4.3%, p<0.001) post intervention. Compared to baseline, expressions of PGC-1∝ and AdipoR1 were increased by approximately three-fold (p=0.019) and two-fold (p=0.003) respectively, along with improved insulin sensitivity (33%, p=0.019) in the HIIT group.

    CONCLUSION: Findings suggest that HIIT possibly improved insulin sensitivity through modulation of PGC-1∝ and AdipoR1. This study also showed that improved metabolic responses can occur despite modest reduction in body weight in overweight/obese individuals undergoing HIIT intervention.

    Matched MeSH terms: Insulin Resistance/physiology*
  5. Tai ES, Lim SC, Chew SK, Tan BY, Tan CE
    Diabetes Res Clin Pract, 2000 Aug;49(2-3):159-68.
    PMID: 10963828 DOI: 10.1016/s0168-8227(00)00152-2
    We studied insulin resistance and beta-cell function with reference to ethnic group, glucose tolerance and other coronary artery disease risk factors in a cross section of the Singapore population which comprises Chinese, Malays and Asian Indians. 3568 individuals aged 18-69 were examined. Blood pressure, anthropometric data, blood lipids, glucose and insulin were assayed in the fasting state. Glucose and serum insulin were measured 2 h after an oral glucose challenge. Insulin resistance and beta-cell function were calculated using homeostasis model assessment. Asian Indians had higher insulin resistance than Chinese or Malays. Impaired glucose tolerance (IGT) and diabetes mellitus (DM) were associated with greater insulin resistance and impaired beta-cell function compared to normal glucose tolerance (NGT). Insulin resistance was positively correlated with blood pressure in women and total cholesterol, LDL cholesterol and triglyceride in both men and women. It was negatively correlated with HDL cholesterol and LDL/apolipoprotein B ratio. beta-cell function showed no significant correlations with the cardiovascular risk factors studied. It appears that both impaired beta-cell function and insulin resistance are important for the development of hyperglycemia whereas insulin resistance alone seems more important in the development of coronary artery disease as it correlates with several known coronary artery disease risk factors.
    Matched MeSH terms: Insulin Resistance*
  6. Adamu HA, Imam MU, Ooi DJ, Esa NM, Rosli R, Ismail M
    BMC Complement Altern Med, 2017 Jan 21;17(1):67.
    PMID: 28109299 DOI: 10.1186/s12906-017-1571-0
    The development of insulin resistance is multifactorial, with maternal pre- and postnatal nutrition having significant influences. In this regard, high fat diet (HFD) feeding in pregnancy has been shown to increase risks of metabolic diseases. Thus, we investigated the effects of supplementation of HFD with germinated brown rice (GBR) and GBR-derived gamma oryzanol-rich extract (OE) on insulin resistance and its epigenetic implications in pregnant rats and their offsprings.
    Matched MeSH terms: Insulin Resistance*
  7. Haskins IN, Chang J, Nor Hanipah Z, Singh T, Mehta N, McCullough AJ, et al.
    Surg Obes Relat Dis, 2018 03;14(3):342-346.
    PMID: 29519663 DOI: 10.1016/j.soard.2017.11.032
    BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) increases the risk of liver cirrhosis and hepatocellular carcinoma and is also strongly correlated with extrahepatic diseases, including cardiovascular disease and type 2 diabetes. This risk of NAFLD among obese individuals who are otherwise metabolically healthy is not well characterized.

    OBJECTIVES: To determine the prevalence and characteristics of NAFLD in individuals with metabolically healthy obesity.

    SETTING: A tertiary, academic, referral hospital.

    METHODS: All patients who underwent bariatric surgery with intraoperative liver biopsy from 2008 to 2015 were identified. Patients with preoperative hypertension, dyslipidemia, or prediabetes/diabetes were excluded to identify a cohort of metabolically healthy obesity patients. Liver biopsy reports were reviewed to determine the prevalence of NAFLD.

    RESULTS: A total of 270 patients (7.0% of the total bariatric surgery patients) met the strict inclusion criteria for metabolically healthy obesity. The average age was 38 ± 10 years and the average body mass index was 47 ± 7 kg/m2. Abnormal alanine aminotransferase (>45 U/L) and asparate aminotransferase levels (>40 U/L) were observed in 28 (10.4%) and 18 (6.7%) patients, respectively. A total of 96 (35.5%) patients had NAFLD with NALFD Activity Scores 0 to 2 (n = 61), 3 to 4 (n = 25), and 5 to 8 (n = 10). A total of 62 (23%) patients had lobular inflammation, 23 (8.5%) had hepatocyte ballooning, 22 (8.2%) had steatohepatitis, and 12 (4.4%) had liver fibrosis.

    CONCLUSION: Even with the use of strict criteria to eliminate all patients with any metabolic problems, a significant proportion of metabolically healthy patients had unsuspected NAFLD. The need and clinical utility of routine screening of obese patients for fatty liver disease and the role of bariatric surgery in the management of NAFLD warrants further investigation.

    Matched MeSH terms: Insulin Resistance/physiology
  8. Eslam M, Alkhouri N, Vajro P, Baumann U, Weiss R, Socha P, et al.
    Lancet Gastroenterol Hepatol, 2021 Oct;6(10):864-873.
    PMID: 34364544 DOI: 10.1016/S2468-1253(21)00183-7
    The term non-alcoholic fatty liver disease (NAFLD), and its definition, have limitations for both adults and children. The definition is most problematic for children, for whom alcohol consumption is usually not a concern. This problematic definition has prompted a consensus to rename and redefine adult NAFLD associated with metabolic dysregulation to metabolic (dysfunction)-associated fatty liver disease (MAFLD). Similarities, distinctions, and differences exist in the causes, natural history, and prognosis of fatty liver diseases in children compared with adults. In this Viewpoint we, an international panel, propose an overarching framework for paediatric fatty liver diseases and an age-appropriate MAFLD definition based on sex and age percentiles. The framework recognises the possibility of other coexisting systemic fatty liver diseases in children. The new MAFLD diagnostic criteria provide paediatricians with a conceptual scaffold for disease diagnosis, risk stratification, and improved clinical and multidisciplinary care, and they align with a definition that is valid across the lifespan.
    Matched MeSH terms: Insulin Resistance/physiology
  9. Sam AH, Sleeth ML, Thomas EL, Ismail NA, Mat Daud N, Chambers E, et al.
    J Clin Endocrinol Metab, 2015 Mar;100(3):1048-52.
    PMID: 25490276 DOI: 10.1210/jc.2014-3450
    CONTEXT AND OBJECTIVE: No current biomarker can reliably predict visceral and liver fat content, both of which are risk factors for cardiovascular disease. Vagal tone has been suggested to influence regional fat deposition. Pancreatic polypeptide (PP) is secreted from the endocrine pancreas under vagal control. We investigated the utility of PP in predicting visceral and liver fat.

    PATIENTS AND METHODS: Fasting plasma PP concentrations were measured in 104 overweight and obese subjects (46 men and 58 women). In the same subjects, total and regional adipose tissue, including total visceral adipose tissue (VAT) and total subcutaneous adipose tissue (TSAT), were measured using whole-body magnetic resonance imaging. Intrahepatocellular lipid content (IHCL) was quantified by proton magnetic resonance spectroscopy.

    RESULTS: Fasting plasma PP concentrations positively and significantly correlated with both VAT (r = 0.57, P < .001) and IHCL (r = 0.51, P < .001), but not with TSAT (r = 0.02, P = .88). Fasting PP concentrations independently predicted VAT after controlling for age and sex. Fasting PP concentrations independently predicted IHCL after controlling for age, sex, body mass index (BMI), waist-to-hip ratio, homeostatic model assessment 2-insulin resistance, (HOMA2-IR) and serum concentrations of triglyceride (TG), total cholesterol (TC), and alanine aminotransferase (ALT). Fasting PP concentrations were associated with serum ALT, TG, TC, low- and high-density lipoprotein cholesterol, and blood pressure (P < .05). These associations were mediated by IHCL and/or VAT. Fasting PP and HOMA2-IR were independently significantly associated with hepatic steatosis (P < .01).

    CONCLUSIONS: Pancreatic polypeptide is a novel predictor of visceral and liver fat content, and thus a potential biomarker for cardiovascular risk stratification and targeted treatment of patients with ectopic fat deposition.

    Matched MeSH terms: Insulin Resistance
  10. Smith PM, Hindmarch CC, Murphy D, Ferguson AV
    Front Psychol, 2014;5:832.
    PMID: 25120524 DOI: 10.3389/fpsyg.2014.00832
    Obesity is a chronic metabolic condition with important public health implications associated with numerous co-morbidities including cardiovascular disease, insulin resistance, and hypertension. The renin angiotensin system (RAS), best known for its involvement in cardiovascular control and body fluid homeostasis has, more recently, been implicated in regulation of energy balance. Interference with the RAS (genetically or pharmacologically) has been shown to influence body weight gain. In this study we investigated the effects of systemic AT1 receptor blockade using losartan on ingestive behaviors and weight gain in diet induced obese (DIO) rats. Prior to losartan administration (30 mg/kg/day) body weight gain remained constant within the DIO animals (3.6 ± 0.3 g/day, n = 8), diet resistant (DR) animals (2.1 ± 0.6 g/day, n = 8) and in the age-matched chow fed control (CHOW) animals (2.8 ± 0.3 g/day, n = 8), Losartan administration abolished body weight gain in animals fed a high fat diet (DIO: -0.4 ± 0.7 g/day, n = 8; and DR: -0.8 ± 0.3 g/day, n = 8) while chow fed animals continued to gain weight (2.2 ± 0.3 g/day, n = 8) as they had previously to oral administration of losartan. This decrease in daily body weight gain was accompanied by a decrease in food intake in the HFD fed animals. Following the removal of losartan, both the DIO and DR animals again showed daily increases in body weight gain and food intake which were similar to control values. Our data demonstrate that oral losartan administration attenuates body weight gain in animals fed a HFD whether the animal is obese (DIO) or not DR while having no effect on body weight gain in age-matched chow fed animals suggesting a protective effect of losartan against body weight gain while on a HFD.
    Matched MeSH terms: Insulin Resistance
  11. Malik A, Cheah PL, Hilmi IN, Chan SP, Goh KL
    J Dig Dis, 2007 Feb;8(1):58-64.
    PMID: 17261137
    Nonalcoholic fatty liver disease (NAFLD) is increasing rapidly in the Asia-Pacific region. There has been a paucity of studies from the region. The aims of this study were to define the demographic, anthropometric, metabolic and histological characteristics of patients with NAFLD in our local population and to determine independent predictors of severe liver fibrosis.
    Matched MeSH terms: Insulin Resistance
  12. Chen Y, Phang WM, Mu AK, Chan CK, Low BS, Sasidharan S, et al.
    Front Pharmacol, 2015;6:211.
    PMID: 26441666 DOI: 10.3389/fphar.2015.00211
    Eurycoma longifolia is a Malaysian native herb that has been widely used as an aphrodisiac and a remedy for andropause. Although the physiological effects of the plant extract were predicted as a result of the alterations in protein expression, the key protein(s) involved in these alterations are still unclear. In the present study, we have investigated the effect of standardized E. longifolia extract on serum protein expression up to 28 days following oral administration in rats. Serum protein profiles were analyzed by 2-dimensional electrophoresis, and altered proteins were identified via mass spectrometry. We observed that alpha-2-HS glycoprotein (AHS) was significantly decreased in the serum of experimentally treated rats compared to pre-treated animals. Moreover, reduction in AHS was confirmed using competitive enzyme-linked immunosorbent assay. AHS expression is known to be associated with insulin resistance and diabetes. Our data indicated that serum AHS was reduced in rats treated with standardized E. longifolia extract, and therefore form a prelude for further investigation into the effects of this natural extract in animal models involving infertility and diabetes.
    Matched MeSH terms: Insulin Resistance
  13. Burska AN, Sakthiswary R, Sattar N
    PLoS One, 2015;10(6):e0128889.
    PMID: 26110878 DOI: 10.1371/journal.pone.0128889
    OBJECTIVE: Beyond the joints, TNFi (tumour necrosis factor inhibitor) therapy may confer systemic benefits in rheumatoid arthritis (RA). Several studies have investigated the role of TNFi on insulin resistance/sensitivity (IR/IS). This question is of general interest given the emerging evidence linking inflammation and insulin resistance. The main aim of this review was to summarise the published data and to determine the effects of TNFi on IR/IS.
    METHODS: We searched the PubMed and ISI Web of Knowledge databases for studies which examined the effects of TNFi on IR/IS. The studies were assessed independently by two reviewers according to a pre-specified protocol. The data on Homeostatic Model Assessment for Insulin resistance (HOMA) and Quantitative Insulin Sensitivity Check Index (QUICKI) were pooled and reported as standard difference in means (SDM) with 95% confidence interval (CI) using a random-effects model.
    RESULTS: A total of eight studies with 260 subjects met the selection criteria. The duration of the studies was from 8 weeks to 12 months. There was statistically significant reduction in HOMA index in six out of eight studies and four reported significant increment in QUICKI. The pooled analysis revealed significant reduction in HOMA [SDM-0.148, 95%CI[-0.278 to -0.017], p=0.026] and increment in QUICKI [SDM 0.312, 95%CI[0.019 to 0.606], p=0.037] with TNFi.
    CONCLUSION: There is emerging evidence to support that TNFi therapy improves IS and reduces IR in RA. Further, well conducted trials are needed to determine if such effects translate to lower incidence of diabetes in RA or other autoimmune conditions on biologic therapy.
    Matched MeSH terms: Insulin Resistance
  14. Shokryzadan P, Rajion MA, Meng GY, Boo LJ, Ebrahimi M, Royan M, et al.
    Crit Rev Food Sci Nutr, 2017 Sep 02;57(13):2737-2748.
    PMID: 26252346 DOI: 10.1080/10408398.2015.1060190
    Conjugated linoleic acid (CLA) is a mixture of isomers of linoleic acid (C18:2 n-6), which is mostly found in the ruminant meat and dairy products. The CLA is known to have many potential health benefits, and considered a potent powerful fatty acid, which is linked to animal and human health. The present work aims to discuss the source and production, mechanism of action, and effects of CLA on humans, poultry, and ruminants by reviewing the recent studies carried out on CLA. Despite most of the recent studies indicating beneficial effects of CLA on improving body weight control parameters, its effects on reducing risk factors of cardiovascular diseases (CVD), inflammation, blood glucose, and insulin are still controversial, and need to be further studied in different hosts.
    Matched MeSH terms: Insulin Resistance
  15. Chia Yee Kang, Salmiah Md Said, Rosliza Abdul Manaf
    MyJurnal
    Introduction: Psychological insulin resistance is the reluctance of diabetes patients or physicians to initiate or in-tensify insulin therapy. The insulin usage among Malaysian type 2 diabetes mellitus (T2DM) patients is low, only 21.4% of audited T2DM patients were on insulin therapy despite 76.2% of the audited T2DM patients had poorly controlled diabetes with HbA1c ≥ 6.5% in year 2012. This study aims to identify the predictors of psychological insulin resistance (PIR) among insulin naïve T2DM patients. Methods: A cross-sectional study using interviewer assisted questionnaires was conducted among adult insulin naïve T2DM patients in government health clinics at a district of Penang, Malaysia. Insulin Treatment Appraisal Scale (ITAS) was used to assess the dependent variable (PIR) and validated self-developed questionnaires were used for assess the independent variables (socio-demographic characteristics, diabetes profile, and individual factors). Multiple linear regression analysis was performed to identify the predictors of PIR. Results: As high as 72.7% out of 385 participants were reluctant to initiate insulin therapy. Emotional factors (fears), perceived personal failure and perceived severity significantly predicted higher PIR whereas perceived benefit and self-efficacy significantly predicted lower PIR. Total 49.8% variability of PIR was explained by the entire individual predictors (R2=49.8%, p = 0.001). Emotional factor was the strongest predictor. Conclusion: This study revealed a high level of PIR among Malaysian T2DM patients. It is vital to tackle the predictors that predict high PIR and strengthen the predictors that lead to low PIR in our health education and health intervention programs.
    Matched MeSH terms: Insulin Resistance
  16. Tan HY, Tan SL, Teo SH, Roebuck MM, Frostick SP, Kamarul T
    PeerJ, 2020;8:e8740.
    PMID: 32587790 DOI: 10.7717/peerj.8740
    Background: Type 2 diabetes mellitus (T2DM) had been reported to be associated with tendinopathy. However, the underlying mechanisms of diabetic tendinopathy still remain largely to be discovered. The purpose of this study was to develop insulin resistance (IR) model on primary human tenocytes (hTeno) culture with tumour necrosis factor-alpha (TNF-α) treatment to study tenocytes homeostasis as an implication for diabetic tendinopathy.

    Methods: hTenowere isolated from human hamstring tendon. Presence of insulin receptor beta (INSR-β) on normal tendon tissues and the hTeno monolayer culture were analyzed by immunofluorescence staining. The presence of Glucose Transporter Type 1 (GLUT1) and Glucose Transporter Type 4 (GLUT4) on the hTeno monolayer culture were also analyzed by immunofluorescence staining. Primary hTeno were treated with 0.008, 0.08, 0.8 and 8.0 µM of TNF-α, with and without insulin supplement. Outcome measures include 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose (2-NBDG) assay to determine the glucose uptake activity; colourimetric total collagen assay to quantify the total collagen expression levels; COL-I ELISA assay to measure the COL-I expression levels and real-time qPCR to analyze the mRNA gene expressions levels of Scleraxis (SCX), Mohawk (MKX), type I collagen (COL1A1), type III collagen (COL3A1), matrix metalloproteinases (MMP)-9 and MMP-13 in hTeno when treated with TNF-α. Apoptosis assay for hTeno induced with TNF-α was conducted using Annexin-V FITC flow cytometry analysis.

    Results: Immunofluorescence imaging showed the presence of INSR-β on the hTeno in the human Achilles tendon tissues and in the hTeno in monolayer culture. GLUT1 and GLUT4 were both positively expressed in the hTeno. TNF-α significantly reduced the insulin-mediated 2-NBDG uptake in all the tested concentrations, especially at 0.008 µM. Total collagen expression levels and COL-I expression levels in hTeno were also significantly reduced in hTeno treated with 0.008 µM of TNF-α. The SCX, MKX and COL1A1 mRNA expression levels were significantly downregulated in all TNF-α treated hTeno, whereas the COL3A1, MMP-9 and MMP-13 were significantly upregulated in the TNF-α treated cells. TNF-α progressively increased the apoptotic cells at 48 and 72 h.

    Conclusion: At 0.008 µM of TNF-α, an IR condition was induced in hTeno, supported with the significant reduction in glucose uptake, as well as significantly reduced total collagen, specifically COL-I expression levels, downregulation of candidate tenogenic markers genes (SCX and MKX), and upregulation of ECM catabolic genes (MMP-9 and MMP-13). Development of novel IR model in hTeno provides an insight on how tendon homeostasis could be affected and can be used as a tool for further discovering the effects on downstream molecular pathways, as the implication for diabetic tendinopathy.

    Matched MeSH terms: Insulin Resistance
  17. Idris Adewale Ahmed, Maryam Abimbola Mikail, Muhammad Ibrahim
    MyJurnal
    Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome strongly associated with
    hyperlipidemia, hypertriglyceridemia, insulin resistance and obesity. The objective of this study is to evaluate the
    potential health benefits of Baccaurea angulata fruit in preventing liver damage due to hypercholesterolemia.
    Twenty-five healthy adult New Zealand White rabbits were assigned to five groups for 90 days diet and
    intervention plan. While four groups (atherogenic groups) were fed 1% cholesterol diet and 0, 0.5, 1.0, and 1.5 mL
    of B. angulata juice kg/per day, the fifth group (negative control) was fed with commercial rabbit pellet only.
    After overnight fasting and sacrifice, the thoracic cavity was opened and the liver was carefully removed,
    specifically observing for any presence of a gross lesion and then immediately fixing in 4% paraformaldehyde for
    at least 48 hours for histopathological analysis. The hepatoprotective effect of B. angulata fruit juice was evident
    in the histological examination of liver tissues. The results indicate the potential health benefits of the antioxidantrich
    B. angulata fruit juice as a functional food with a therapeutic effect against hypercholesterolemia-induced
    liver injury.
    Matched MeSH terms: Insulin Resistance
  18. John CM, Mohamed Yusof NIS, Abdul Aziz SH, Mohd Fauzi F
    Int J Mol Sci, 2018 Dec 05;19(12).
    PMID: 30563117 DOI: 10.3390/ijms19123894
    Gestational diabetes mellitus (GDM) carries many risks, where high blood pressure, preeclampsia and future type II diabetes are widely acknowledged, but less focus has been placed on its effect on cognitive function. Although the multifactorial pathogenesis of maternal cognitive impairment is not completely understood, it shares several features with type 2 diabetes mellitus (T2DM). In this review, we discuss some key pathophysiologies of GDM that may lead to cognitive impairment, specifically hyperglycemia, insulin resistance, oxidative stress, and neuroinflammation. We explain how these incidents: (i) impair the insulin-signaling pathway and/or (ii) lead to cognitive impairment through hyperphosphorylation of τ protein, overexpression of amyloid-β and/or activation of microglia. The aforementioned pathologies impair the insulin-signaling pathway primarily through serine phosphorylation of insulin receptor substances (IRS). This then leads to the inactivation of the phosphatidylinositol 3-kinase/Protein kinase B (PI3K/AKT) signaling cascade, which is responsible for maintaining brain homeostasis and normal cognitive functioning. PI3K/AKT is crucial in maintaining normal cognitive function through the inactivation of glycogen synthase kinase 3β (GSκ3β), which hyperphosphorylates τ protein and releases pro-inflammatory cytokines that are neurotoxic. Several biomarkers were also highlighted as potential biomarkers of GDM-related cognitive impairment such as AGEs, serine-phosphorylated IRS-1 and inflammatory markers such as tumor necrosis factor α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), leptin, interleukin 1β (IL-1β), and IL-6. Although GDM is a transient disease, its complications may be long-term, and hence increased mechanistic knowledge of the molecular changes contributing to cognitive impairment may provide important clues for interventional strategies.
    Matched MeSH terms: Insulin Resistance
  19. Syukri Y, Taher M, Martien R, Lukitaningsih E, Nugroho AE, Zakaria ZA
    Adv Pharm Bull, 2021 Jan;11(1):171-180.
    PMID: 33747864 DOI: 10.34172/apb.2021.018
    Purpose:
    Insulin resistance is a characteristic of non-insulin-dependent diabetes mellitus associated with obesity and caused by the failure of pancreatic beta cells to secrete sufficient amount of insulin. Andrographolide (AND) improves beta-cell reconstruction and inhibits fat-cell formation. This research aimed to improve the delivery of water-insoluble AND in self-nanoemulsifying (ASNE) formulation, tested in streptozotocin (STZ)-induced diabetic rats and 3T3-L1 preadipocyte cells.
    Methods:
    A conventional formulation of AND in suspension was used as a control. The experimental rats were orally administered with self-nanoemulsifying (SNE) and suspension of AND for 8 days. Measurements were performed to evaluate blood glucose levels in preprandial and postprandial conditions. Immunohistochemistry was used to assess the process of islet beta cell reconstruction. In vitro study was performed using cell viability and adipocyte differentiation assay to determine the delivery of AND in the formulation.
    Results:
    ASNE lowered blood glucose levels (day 4) faster than AND suspension (day 6). The histological testing showed that ASNE could regenerate pancreatic beta cells. Therefore, ASNE ameliorated pancreatic beta cells. The in vitro evaluation indicated the inhibition of adipocyte differentiation by both AND and ASNE, which occurred in a time-dependent manner. ASNE formulation had better delivery than AND.
    Conclusion:
    ASNE could improve the antidiabetic activity by lowering blood glucose levels, enhancing pancreatic beta cells, and inhibiting lipid formation in adipocyte cells.
    Matched MeSH terms: Insulin Resistance
  20. Chua GHI, Phang SCW, Wong YO, Ho LS, Palanisamy UD, Abdul Kadir K
    Nutrients, 2020 Nov 27;12(12).
    PMID: 33261162 DOI: 10.3390/nu12123659
    Malaysian national morbidity surveys on diabetic prevalence have shown ethnical variation among prediabetic and diabetic populations. In our attempt to understand this variation, we studied the α-tocopherol, insulin resistance, β-cell function and receptor of advanced glycation end-products (RAGE) levels, as risk factors of type 2 diabetes, among the different ethnicities. In total, 299 subjects of Malay, Chinese, Indian and aboriginal Orang Asli (OA) heritage were recruited from urban and rural areas of Malaysia by stratified random sampling. Serum α-tocopherol concentrations were measured using high performance liquid chromatography (HPLC) and insulin concentrations were measured using enzyme-linked immunosorbent assay (ELISA). In subjects with pre-diabetes, OAs had the highest α-tocopherol level, followed by Chinese and Malays (0.8938, 0.8564 and 0.6948 respectively; p < 0.05). In diabetic subjects, Malays had significantly higher RAGE levels compared to Chinese and Indians (5579.31, 3473.40 and 3279.52 pg/mL respectively, p = 0.001). Low α-tocopherol level (OR = 3.021, p < 0.05) and high insulin resistance (OR = 2.423, p < 0.05) were linked strongly to the development of pre-diabetes. Low β-cell function (OR = 5.657, p < 0.001) and high RAGE level (OR = 3.244, p < 0.05) were linked strongly to the development of diabetes from pre-diabetes. These factors might be involved in the development of diabetes, along with genetic and environmental factors.
    Matched MeSH terms: Insulin Resistance
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