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  1. Diabetes mellitus exacerbates advanced glycation end product accumulation in the veins of end-stage renal failure patients
    Nazratun N, Mahmood AA, Kuppusamy UR, Ahmad TS, Tan SY
    Vasc Med, 2006 Nov;11(4):245-50.
    PMID: 17390548
    The excess accumulation of advanced glycation end products (AGEs) contributes to the chronic complications of type 2 diabetes mellitus (DM) and renal failure. Biopsy specimens (n = 184) of arterial (n = 92) and venous (n = 92) tissues were obtained (radial artery and cephalic vein) from end-stage renal disease (ESRD) patients with or without DM and normal healthy subjects (n = 12) requiring surgery (trauma patients). Immunohistochemical assessment of the blood vessels revealed the presence of pentosidine (AGE marker) in both veins and arteries in 72% of the ESRD patients. The percentage of arteries and veins that showed positive pentosidine staining in ESRD patients with type 2 DM alone was 100% and 92% respectively, in the non-diabetic ESRD patients it was < 70% (for arteries and veins), and in the ESRD patients with hypertension as an additional co-morbidity to type 2 DM it was 70% and 82%, respectively. The veins of ESRD patients with DM showed a strong (+++) positive staining and very strong (++++) positive staining was observed in the patients with DM and hypertension. Only mild (+) or moderate (++) pentosidine staining intensity was observed in the arteries of ESRD patients without or with comorbidities, respectively. The accumulation of AGE in the vein rather than the artery may be a better reflection of the extent of complications of ESRD.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism*
  2. Fulltext Correlation between fasting plasma glucose, post prandial glucose and glycated haemoglobin and fructosamine
    Rosediani M, Azidah AK, Mafauzy M
    Med J Malaysia, 2006 Mar;61(1):67-71.
    PMID: 16708736 MyJurnal
    This study was done to determine the correlation between glucose monitoring by fasting blood glucose or 2 hours postprandial blood glucose with HbA1c and fructosamine in type 2 diabetic patients. A total of 82 patients from the Primary Care Clinic were enrolled in the study. Fasting blood was drawn for fasting plasma glucose (FPG), glycated haemoglobin (HbA1c) and fructosamine. Two hours after a standard breakfast, blood was again drawn for prandial plasma glucose (PPG). Both PPG and FPG significantly correlated with both HbA1c and fructosamine but PPG showed better correlation to HbA1c than FPG (r= 0.604 vs.0.575) whereas that of FPG and PPG were equally correlated to fructosamine (r= 0.566 vs. 0.551). In predicting good glycaemic control (HbA1c < 7.0%), the sensitivity, specificity and positive predictive value of PPG were 75.0%, 80.6% and 82.5% whereas FPG were 81.8%, 58.3% and 70.6% respectively. These results show that PPG correlated better than FPG to HbA1c and both equally correlated to fructosamine levels. Thus, PPG predicted overall glycaemic control better than FPG. Compared to HbA1c, fructosamine correlated least well with mean glucose profiles. Hence, using HbAlc in monitoring overall glycaemic control is better than fructosamine.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism*
  3. Fulltext Triple negative breast cancer: the role of metabolic pathways
    Dean SJ, Rhodes A
    Malays J Pathol, 2014 Dec;36(3):155-62.
    PMID: 25500513 MyJurnal
    The incidence of breast cancer in Malaysia and other Asian countries is on the increase, reflecting lifestyle changes some of which are known risk factors for the development of breast cancer. Most breast cancers are amenable to adjuvant therapies that target hormone receptors or HER2 receptors on the surface of the cancer cells and bring about significant improvement in survival. However, approximately 17% of Malaysian women with breast cancer, present with tumours that are devoid of these receptors and are consequently termed 'triple negative' breast cancers. These triple negative breast cancers typically occur in women of a younger age than receptor positive cancers, are predominantly of high grade tumours and the prognosis is usually poor. There is therefore a pressing need to understand the biological pathways that drive these tumours, in order that effective strategies are developed to treat these aggressive tumours. With the increasing affluence of developing countries, obesity and Type II Diabetes are also on the rise. These diseases are associated with an increased risk of developing a range of cancers including those of the breast. In particular, the metabolic syndrome has been shown to be associated with triple negative breast cancer. This article reviews some of the metabolic pathways and biomarkers which have been shown to be aberrantly expressed in triple negative breast cancer and highlights some of the ongoing work in this area.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism*
  4. Diabetes improvement and resolution following laparoscopic vertical sleeve gastrectomy (LVSG) versus laparoscopic Roux-en-Y gastric bypass (LRYGB) procedures: a systematic review of randomized controlled trials
    Osland E, Yunus RM, Khan S, Memon B, Memon MA
    Surg Endosc, 2017 04;31(4):1952-1963.
    PMID: 27623997 DOI: 10.1007/s00464-016-5202-5
    BACKGROUND: The prevalence of type 2 diabetes is growing in both developed and developing countries and is strongly linked with the prevalence of obesity. Bariatric surgical procedures such as laparoscopic vertical sleeve gastrectomy (LVSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) are increasingly being utilized to manage related comorbid chronic conditions, including type 2 diabetes.

    METHODS: A systematic review of randomized controlled trials (RCTs) was undertaken using the PRISMA guidelines to investigate the postoperative impact on diabetes resolution following LVSG versus LRYGB.

    RESULTS: Seven RCTs involving a total of 732 patients (LVSG n = 365, LRYGB n = 367) met inclusion criteria. Significant diabetes resolution or improvement was reported with both procedures across all time points. Similarly, measures of glycemic control (HbA1C and fasting blood glucose levels) improved with both procedures, with earlier improvements noted in LRYGB that stabilized and did not differ from LVSG at 12 months postoperatively. Early improvements in measures of insulin resistance in both procedures were also noted in the studies that investigated this.

    CONCLUSIONS: This systematic review of RCTs suggests that both LVSG and LRYGB are effective in resolving or improving preoperative type 2 diabetes in obese patients during the reported 3- to 5-year follow-up periods. However, further studies are required before longer-term outcomes can be elucidated. Areas identified that need to be addressed for future studies on this topic include longer follow-up periods, standardized definitions and time point for reporting, and financial analysis of outcomes obtained between surgical procedures to better inform procedure selection.

    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism*
  5. The impact of sleep amount and sleep quality on glycemic control in type 2 diabetes: A systematic review and meta-analysis
    Lee SWH, Ng KY, Chin WK
    Sleep Med Rev, 2017 02;31:91-101.
    PMID: 26944909 DOI: 10.1016/j.smrv.2016.02.001
    Recent epidemiological studies have suggested that there is an association between glycemic control and sleep disturbances in patients with type 2 diabetes, but the extent is unclear. A systematic literature search was performed in nine electronic databases from inception until August 2015 without any language restriction. The search identified 20 studies (eight studies reporting duration of sleep and 15 studies evaluating sleep quality), and 15 were included in the meta-analysis. Short and long sleep durations were associated with an increased hemoglobin A1c (HbA1c) (weighted mean difference (WMD): 0.23% [0.10-0.36], short sleep; WMD: 0.13% [0.02-0.25], long sleep) compared to normal sleep, suggesting a U-shaped dose-response relationship. Similarly, poor sleep quality was associated with an increased HbA1c (WMD: 0.35% [0.12-0.58]). Results of this study suggest that amount of sleep as well as quality of sleep is important in the metabolic function of type 2 diabetes patients. Further studies are needed to identify for the potential causal role between sleep and altered glucose metabolism.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism*
  6. Fulltext Relationship between apoptotic markers (Bax and Bcl-2) and biochemical markers in type 2 diabetes mellitus
    Hasnan J, Yusof MI, Damitri TD, Faridah AR, Adenan AS, Norbaini TH
    Singapore Med J, 2010 Jan;51(1):50-5.
    PMID: 20200776
    Bax is essential for apoptosis in normal cells. However, overexpression of Bcl-2 enhances cell survival by suppressing apoptosis in cells subjected to apoptosis-inducing stimuli. The aim of this study was to examine the expression of apoptotic (Bax and Bcl-2) and biochemical markers in type 2 diabetics mellitus.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism*
  7. Fulltext Palm Fruit Bioactives augment expression of Tyrosine Hydroxylase in the Nile Grass Rat basal ganglia and alter the colonic microbiome
    Weinberg RP, Koledova VV, Subramaniam A, Schneider K, Artamonova A, Sambanthamurthi R, et al.
    Sci Rep, 2019 Dec 09;9(1):18625.
    PMID: 31819070 DOI: 10.1038/s41598-019-54461-y
    Tyrosine hydroxylase (TH) catalyzes the hydroxylation of L-tyrosine to L-DOPA. This is the rate-limiting step in the biosynthesis of the catecholamines - dopamine (DA), norepinephrine (NE), and epinephrine (EP). Catecholamines (CA) play a key role as neurotransmitters and hormones. Aberrant levels of CA are associated with multiple medical conditions, including Parkinson's disease. Palm Fruit Bioactives (PFB) significantly increased the levels of tyrosine hydroxylase in the brain of the Nile Grass rat (NGR), a novel and potentially significant finding, unique to PFB among known botanical sources. Increases were most pronounced in the basal ganglia, including the caudate-putamen, striatum and substantia nigra. The NGR represents an animal model of diet-induced Type 2 Diabetes Mellitus (T2DM), exhibiting hyperglycemia, hyperinsulinemia, and insulin resistance associated with hyperphagia and accelerated postweaning weight gain induced by a high-carbohydrate diet (hiCHO). The PFB-induced increase of TH in the basal ganglia of the NGR was documented by immuno-histochemical staining (IHC). This increase in TH occurred equally in both diabetes-susceptible and diabetes-resistant NGR fed a hiCHO. PFB also stimulated growth of the colon microbiota evidenced by an increase in cecal weight and altered microbiome.  The metabolites of colon microbiota, e.g. short-chain fatty acids, may influence the brain and behavior significantly.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism
  8. Fulltext Role of exercise in the management of diabetes mellitus: the global scenario
    Thent ZC, Das S, Henry LJ
    PLoS One, 2013;8(11):e80436.
    PMID: 24236181 DOI: 10.1371/journal.pone.0080436
    Background: Exercise training programs have emerged as a useful therapeutic regimen for the management of type 2 diabetes mellitus (T2DM). Majority of the Western studies highlighted the effective role of exercise in T2DM. Therefore, the main aim was to focus on the extent, type of exercise and its clinical significance in T2DM in order to educate the clinicians from developing countries, especially in Asians.

    Methods: Pubmed, Science Direct, Scopus, ISI Web of Knowledge and Google scholar were searched using the terms "type 2 diabetes mellitus," "type 2 DM," "exercise," and/or "physical activity," and "type 2 diabetes mellitus with exercise." Only clinical or human studies published in English language between 2000 and 2012 were included. Certain criteria were assigned to achieve appropriate results.

    Results: Twenty five studies met the selected criteria. The majority of the studies were randomized controlled trial study design (65%). Most of the aerobic exercise based studies showed a beneficial effect in T2DM. Resistance exercise also proved to have positive effect on T2DM patients. Minimal studies related to other types of exercises such as yoga classes, joba riding and endurance-type exercise were found. On the other hand, United States of America (USA) showed strong interest of exercise management towards T2DM.

    Conclusion: Aerobic exercise is more common in clinical practice compared to resistance exercise in managing T2DM. Treatment of T2DM with exercise training showed promising role in USA. A large number of researches are mandatory in the developing countries for incorporating exercise in the effective management of T2DM.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism
  9. Self-care practices of Malaysian adults with diabetes and sub-optimal glycaemic control
    Tan MY, Magarey J
    Patient Educ Couns, 2008 Aug;72(2):252-67.
    PMID: 18467068 DOI: 10.1016/j.pec.2008.03.017
    OBJECTIVE: To investigate the self-care practices of Malaysian adults with diabetes and sub-optimal glycaemic control.
    METHODS: Using a one-to-one interviewing approach, data were collected from 126 diabetic adults from four settings. A 75-item questionnaire was used to assess diabetes-related knowledge and self-care practices regarding, diet, medication, physical activity and self-monitoring of blood glucose (SMBG).
    RESULTS: Most subjects had received advice on the importance of self-care in the management of their diabetes and recognised its importance. Sixty-seven subjects (53%) scored below 50% in their diabetes-related knowledge. Subjects who consumed more meals per day (80%), or who did not include their regular sweetened food intakes in their daily meal plan (80%), or who were inactive in daily life (54%), had higher mean fasting blood glucose levels (p=0.04). Subjects with medication non-adherence (46%) also tended to have higher fasting blood glucose levels. Only 15% of the subjects practiced SMBG. Predictors of knowledge deficit and poor self-care were low level of education (p = <0.01), older subjects (p=0.04) and Type 2 diabetes subjects on oral anti-hyperglycaemic medication (p = <0.01).
    CONCLUSION: There were diabetes-related knowledge deficits and inadequate self-care practices among the majority of diabetic patients with sub-optimal glycaemic control.
    PRACTICE IMPLICATIONS: This study should contribute to the development of effective education strategies to promote health for adults with sub-optimal diabetes control.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism
  10. Antidiabetic and antidyslipidemic potential of Echinops echinatus in rat models of type I and type II diabetes
    Chaudhry SRY, Akram A, Aslam N, Wajid M, Iqbal Z, Nazir I, et al.
    Pak J Pharm Sci, 2019 Mar;32(2):505-514.
    PMID: 31081759
    Echinops echinatus is traditionally an important plant that finds its extensive use as a diuretic, anti-inflammatory, anti-pyretic, nerve tonic, abortifacient, aphrodisiac, antiasthmatic, and antidiabetic agent. The current study investigates protection against the hyperglycemia and dyslipidemia in alloxan-induced (type I diabetes) and fructose-fed insulin resistance (type II diabetes) models of diabetes treated with aqueous methanolic root extract of E. echinatus (Ee.Cr). Albino rats were treated orally with Ee.Cr at doses 100, 300 and 500mg/kg. The fasting blood glucose was measured by glucometer, while standard kits were used to determine the levels of serum total cholesterol, triglycerides and HDL. The administration of Ee.Cr significantly (P<0.001) reduced the FBG concentration in a dose-dependent pattern in alloxan-induced and fructose-fed diabetic rats. The Ee.Cr also corrected the dyslipidemia associated with fructose and alloxan-induced diabetes by significantly (P<0.001) decreasing the concentration of serum total cholesterol, triglycerides, and LDL and by increasing HDL concentration. Ee.Cr also significantly (P<0.001) improved the glucose tolerance in fructose-fed rats. We conclude that Ee.Cr has antidiabetic and antidyslipidemic effects in both insulin-dependent alloxan-induced diabetes and fructose-induced insulin resistance diabetes rat models.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism
  11. Fulltext Comparison of Structured Nutrition Therapy for Ramadan with Standard Care in Type 2 Diabetes Patients
    Mohd Yusof BN, Wan Zukiman WZHH, Abu Zaid Z, Omar N, Mukhtar F, Yahya NF, et al.
    Nutrients, 2020 Mar 19;12(3).
    PMID: 32204476 DOI: 10.3390/nu12030813
    (1) Background: Structured nutrition therapy (NT) is essential for the management of type 2 diabetes (T2D), but the optimal delivery during Ramadan fasting remains unclear. The present study aimed to evaluate the effect of structured NT program versus standard care in patients with T2D during Ramadan. (2) Methods: The present study was an 8-week, parallel, non-randomized study with patients' preference design involving 64 patients with T2D. The participants were asked to choose their preferred group, i.e., structured NT (Structured Ramadan NT, sRNT) or standard care (SC). The participants in the sRNT group received a Ramadan-focused nutrition plan, including a diabetes-specific formula throughout the study, whereas the patients in the SC group received standard nutrition care. Study outcomes included clinical outcomes and quality of life (QoL). Data was analyzed using two-way repeated-measures ANOVA and linear mixed-effects model. (3) Results: More than half of the participants (n = 38, 63%) chose sRNT as their preferred group. Both groups had comparable baseline characteristics. After 8-weeks of the respective intervention, participants in the sRNT group had lower levels of fasting plasma glucose (-0.9 ± 0.3 mmol/L vs. 0.2 ± 0.3 mmol/L, p < 0.05), triglycerides (-0.21 ± 0.08 mmol/L vs. 0.20 ± 0.17 mmol/L, p < 0.05), and self-monitoring glucose at pre-dawn (6.9 mmol/L vs. 7.8 mmol/L, p < 0.05) and pre-bedtime (7.6 mmol/L vs. 8.6 mmol/L, p < 0.05) than participants in the SC group. Although not different between groups, HbA1c levels decreased significantly in the sRNT (-0.72 ± 0.16%, p < 0.001) but not in the SC group (-0.35 ± 0.24%, p = 0.155). QoL and satisfaction scores improved significantly in sRNT group, but not in SC group. (4) Conclusions: The structured NT regimen for Ramadan is a feasible and beneficial program for T2D patients observing Ramadan fasting as it showed an improvement in clinical outcomes and QoL.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism
  12. Fulltext Natural Phyto-Bioactive Compounds for the Treatment of Type 2 Diabetes: Inflammation as a Target
    Gothai S, Ganesan P, Park SY, Fakurazi S, Choi DK, Arulselvan P
    Nutrients, 2016 Aug 04;8(8).
    PMID: 27527213 DOI: 10.3390/nu8080461
    Diabetes is a metabolic, endocrine disorder which is characterized by hyperglycemia and glucose intolerance due to insulin resistance. Extensive research has confirmed that inflammation is closely involved in the pathogenesis of diabetes and its complications. Patients with diabetes display typical features of an inflammatory process characterized by the presence of cytokines, immune cell infiltration, impaired function and tissue destruction. Numerous anti-diabetic drugs are often prescribed to diabetic patients, to reduce the risk of diabetes through modulation of inflammation. However, those anti-diabetic drugs are often not successful as a result of side effects; therefore, researchers are searching for efficient natural therapeutic targets with less or no side effects. Natural products' derived bioactive molecules have been proven to improve insulin resistance and associated complications through suppression of inflammatory signaling pathways. In this review article, we described the extraction, isolation and identification of bioactive compounds and its molecular mechanisms in the prevention of diabetes associated complications.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism
  13. Endothelium dependent hyperpolarization-type relaxation compensates for attenuated nitric oxide-mediated responses in subcutaneous arteries of diabetic patients
    Mokhtar SS, Vanhoutte PM, Leung SW, Yusof MI, Wan Sulaiman WA, Mat Saad AZ, et al.
    Nitric Oxide, 2016 Feb 29;53:35-44.
    PMID: 26768833 DOI: 10.1016/j.niox.2015.12.007
    Diabetes impairs endothelium-dependent relaxations. The present study evaluated the contribution of different endothelium-dependent relaxing mechanisms to the regulation of vascular tone in subcutaneous blood vessels of humans with Type 2 diabetes mellitus. Subcutaneous arteries were isolated from tissues of healthy controls and diabetics. Vascular function was determined using wire myography. Expressions of proteins were measured by Western blotting and immunostaining. Endothelium-dependent relaxations to acetylcholine were impaired in arteries from diabetics compared to controls (P = 0.009). Acetylcholine-induced nitric oxide (NO)-mediated relaxations [in the presence of an inhibitor of cyclooxygenases (COX; indomethacin) and small and intermediate conductance calcium-activated potassium channel blockers (UCL1684 and TRAM 34, respectively)] were attenuated in arteries from diabetics compared to controls (P type relaxations [in the presence of indomethacin and the NO synthase blocker, l-NAME] were augmented in arteries from diabetics compared to controls (P = 0.003). Endothelium-independent relaxations to sodium nitroprusside (NO donor) and salbutamol (β-adrenoceptor agonist) were preserved, but those to prostacyclin were attenuated in diabetics compared to controls (P = 0.017). In arteries of diabetics, protein expressions of endothelial NO synthase, prostacyclin synthase and prostacyclin receptors were decreased, but those of COX-2 were increased. These findings suggest that in human diabetes, the impairment of endothelium-dependent relaxations is caused by a diminished NO bioavailability; however, EDH appears to compensate, at least in part, for this dysfunction.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism*
  14. Fulltext Medicinal Potential of Isoflavonoids: Polyphenols That May Cure Diabetes
    Ahmed QU, Ali AHM, Mukhtar S, Alsharif MA, Parveen H, Sabere ASM, et al.
    Molecules, 2020 Nov 24;25(23).
    PMID: 33255206 DOI: 10.3390/molecules25235491
    In recent years, there is emerging evidence that isoflavonoids, either dietary or obtained from traditional medicinal plants, could play an important role as a supplementary drug in the management of type 2 diabetes mellitus (T2DM) due to their reported pronounced biological effects in relation to multiple metabolic factors associated with diabetes. Hence, in this regard, we have comprehensively reviewed the potential biological effects of isoflavonoids, particularly biochanin A, genistein, daidzein, glycitein, and formononetin on metabolic disorders and long-term complications induced by T2DM in order to understand whether they can be future candidates as a safe antidiabetic agent. Based on in-depth in vitro and in vivo studies evaluations, isoflavonoids have been found to activate gene expression through the stimulation of peroxisome proliferator-activated receptors (PPARs) (α, γ), modulate carbohydrate metabolism, regulate hyperglycemia, induce dyslipidemia, lessen insulin resistance, and modify adipocyte differentiation and tissue metabolism. Moreover, these natural compounds have also been found to attenuate oxidative stress through the oxidative signaling process and inflammatory mechanism. Hence, isoflavonoids have been envisioned to be able to prevent and slow down the progression of long-term diabetes complications including cardiovascular disease, nephropathy, neuropathy, and retinopathy. Further thoroughgoing investigations in human clinical studies are strongly recommended to obtain the optimum and specific dose and regimen required for supplementation with isoflavonoids and derivatives in diabetic patients.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism
  15. Fulltext Action of Phytochemicals on Insulin Signaling Pathways Accelerating Glucose Transporter (GLUT4) Protein Translocation
    Sayem ASM, Arya A, Karimian H, Krishnasamy N, Ashok Hasamnis A, Hossain CF
    Molecules, 2018 Jan 28;23(2).
    PMID: 29382104 DOI: 10.3390/molecules23020258
    Diabetes is associated with obesity, generally accompanied by a chronic state of oxidative stress and redox imbalances which are implicated in the progression of micro- and macro-complications like heart disease, stroke, dementia, cancer, kidney failure and blindness. All these complications rise primarily due to consistent high blood glucose levels. Insulin and glucagon help to maintain the homeostasis of glucose and lipids through signaling cascades. Pancreatic hormones stimulate translocation of the glucose transporter isoform 4 (GLUT4) from an intracellular location to the cell surface and facilitate the rapid insulin-dependent storage of glucose in muscle and fat cells. Malfunction in glucose uptake mechanisms, primarily contribute to insulin resistance in type 2 diabetes. Plant secondary metabolites, commonly known as phytochemicals, are reported to have great benefits in the management of type 2 diabetes. The role of phytochemicals and their action on insulin signaling pathways through stimulation of GLUT4 translocation is crucial to understand the pathogenesis of this disease in the management process. This review will summarize the effects of phytochemicals and their action on insulin signaling pathways accelerating GLUT4 translocation based on the current literature.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism*
  16. Fulltext Current Status of Endoplasmic Reticulum Stress in Type II Diabetes
    Mustapha S, Mohammed M, Azemi AK, Jatau AI, Shehu A, Mustapha L, et al.
    Molecules, 2021 Jul 19;26(14).
    PMID: 34299638 DOI: 10.3390/molecules26144362
    The endoplasmic reticulum (ER) plays a multifunctional role in lipid biosynthesis, calcium storage, protein folding, and processing. Thus, maintaining ER homeostasis is essential for cellular functions. Several pathophysiological conditions and pharmacological agents are known to disrupt ER homeostasis, thereby, causing ER stress. The cells react to ER stress by initiating an adaptive signaling process called the unfolded protein response (UPR). However, the ER initiates death signaling pathways when ER stress persists. ER stress is linked to several diseases, such as cancer, obesity, and diabetes. Thus, its regulation can provide possible therapeutic targets for these. Current evidence suggests that chronic hyperglycemia and hyperlipidemia linked to type II diabetes disrupt ER homeostasis, thereby, resulting in irreversible UPR activation and cell death. Despite progress in understanding the pathophysiology of the UPR and ER stress, to date, the mechanisms of ER stress in relation to type II diabetes remain unclear. This review provides up-to-date information regarding the UPR, ER stress mechanisms, insulin dysfunction, oxidative stress, and the therapeutic potential of targeting specific ER stress pathways.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism*
  17. Discovery of α-Glucosidase Inhibitors from Marine Microorganisms: Optimization of Culture Conditions and Medium Composition
    Trang NTH, Tang DYY, Chew KW, Linh NT, Hoang LT, Cuong NT, et al.
    Mol Biotechnol, 2021 Nov;63(11):1004-1015.
    PMID: 34185249 DOI: 10.1007/s12033-021-00362-3
    Various studies showed that the suppression of α-glucosidase activity can impede the glucose absorption in our body, and therefore, it can be used to treat type 2 diabetes. Hence, the compounds with anti-α-glucosidase have gained considerable attention because of their potential application in diabetes treatment. In previous literature studies, these anti-α-glucosidase compounds were extracted from plants and fungus. Less studies are being conducted to identify the anti-α-glucosidase compounds in the microbial community. In this study, 23 marine bacterial strains were screened for their potential to suppress the α-glucosidase activity. The highest inhibitory activity was exhibited by isolated L06 which was identified as Oceanimonas smirnovii EBL6. The cultivation conditions, such as temperature and pH, were optimized to increase the production of α-glucosidase inhibitors by Oceanimonas smirnovii EBL6 strain. The result findings showed that the highest yield of α-glucosidase inhibitors can be obtained at the culture time of 120 h, fermentation temperature of 30 °C, and pH 4.6. Under these conditions, the inhibitory activity of α-glucosidase can reach 81%. The IC50 of n-butanol extract was 13.89 μg/ml, while standard acarbose was 31.16 μg/ml. Overall, these findings suggest that Oceanimonas smirnovii produces α-glucosidase inhibitors and could been applied in the biochemical and medicinal fields in the future.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism
  18. Metabolomics - the complementary field in systems biology: a review on obesity and type 2 diabetes
    Abu Bakar MH, Sarmidi MR, Cheng KK, Ali Khan A, Suan CL, Zaman Huri H, et al.
    Mol Biosyst, 2015 Jul;11(7):1742-74.
    PMID: 25919044 DOI: 10.1039/c5mb00158g
    Metabolomic studies on obesity and type 2 diabetes mellitus have led to a number of mechanistic insights into biomarker discovery and comprehension of disease progression at metabolic levels. This article reviews a series of metabolomic studies carried out in previous and recent years on obesity and type 2 diabetes, which have shown potential metabolic biomarkers for further evaluation of the diseases. Literature including journals and books from Web of Science, Pubmed and related databases reporting on the metabolomics in these particular disorders are reviewed. We herein discuss the potential of reported metabolic biomarkers for a novel understanding of disease processes. These biomarkers include fatty acids, TCA cycle intermediates, carbohydrates, amino acids, choline and bile acids. The biological activities and aetiological pathways of metabolites of interest in driving these intricate processes are explained. The data from various publications supported metabolomics as an effective strategy in the identification of novel biomarkers for obesity and type 2 diabetes. Accelerating interest in the perspective of metabolomics to complement other fields in systems biology towards the in-depth understanding of the molecular mechanisms underlying the diseases is also well appreciated. In conclusion, metabolomics can be used as one of the alternative approaches in biomarker discovery and the novel understanding of pathophysiological mechanisms in obesity and type 2 diabetes. It can be foreseen that there will be an increasing research interest to combine metabolomics with other omics platforms towards the establishment of detailed mechanistic evidence associated with the disease processes.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism*
  19. The influence of selenium status on body composition, oxidative DNA damage and total antioxidant capacity in newly diagnosed type 2 diabetes mellitus: A case-control study
    Othman FB, Mohamed HJBJ, Sirajudeen KNS, Noh MFBM, Rajab NF
    J Trace Elem Med Biol, 2017 Sep;43:106-112.
    PMID: 28065595 DOI: 10.1016/j.jtemb.2016.12.009
    Selenium is involved in the complex system of defense against oxidative stress in diabetes through its biological function of selenoproteins and the antioxidant enzyme. A case-control study was carried out to determine the association of plasma selenium with oxidative stress and body composition status presented in Type 2 Diabetes Mellitus (T2DM) patient and healthy control. This study involved 82 newly diagnosed T2DM patients and 82 healthy controls. Plasma selenium status was determined with Graphite Furnace Atomic Absorption Spectrometry. Body Mass Index, total body fat and visceral fat was assessed for body composition using Body Composition Analyzer (TANITA). Oxidative DNA damage and total antioxidant capacity were determined for oxidative stress biomarker status. In age, gender and BMI adjustment, no significant difference of plasma selenium level between T2DM and healthy controls was observed. There was as a significant difference of Oxidative DNA damage and total antioxidant capacity between T2DM patients and healthy controls with tail DNA% 20.62 [95% CI: 19.71,21.49] (T2DM), 17.67 [95% CI: 16.87,18.56] (control); log tail moment 0.41[95% CI: 0.30,0.52] (T2DM), 0.41[95% CI: 0.30,0.52] (control); total antioxidant capacity 0.56 [95% CI: 0.54,0.58] (T2DM), 0.60 [95% CI: 0.57,0.62] (control). Waist circumference, BMI, visceral fat, body fat and oxidative DNA damage in the T2DM group were significantly lower in the first plasma selenium tertile (38.65-80.90μg/L) compared to the second (80.91-98.20μg/L) and the third selenium tertiles (98.21-158.20μg/L). A similar trend, but not statistically significant, was observed in the control group.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism*
  20. Metabolic and biochemical changes in streptozotocin induced obese-diabetic rats treated with Phyllanthus niruri extract
    Mediani A, Abas F, Maulidiani M, Khatib A, Tan CP, Ismail IS, et al.
    J Pharm Biomed Anal, 2016 Sep 05;128:302-312.
    PMID: 27318080 DOI: 10.1016/j.jpba.2016.06.003
    Herbal medicine has been proven to be an effective therapy offering a variety of benefits, such as moderate reduction in hypoglycemia, in the treatment and prevention of obesity and diabetes. Phyllanthus niruri has been used as a treatment for diabetes mellitus. Herein, the induction of type 2 diabetes in Sprague-Dawley rats was achieved by a low dose of streptozotocin (STZ) (25mg/kgbw). Here, we evaluated the in vivo antidiabetic properties of two concentrations (250 and 500mg/kg bw) of P. niruri via metabolomics approach. The administration of 500mg/kgbw of P. niruri extract caused the metabolic disorders of obese diabetic rats to be improved towards the normal state. The extract also clearly decreased the serum glucose level and improved the lipid profile in obese diabetic rats. The results of this study may contribute towards better understanding the molecular mechanism of this medicinal plant in managing diabetes mellitus.
    Matched MeSH terms: Diabetes Mellitus, Type 2/metabolism
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