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  1. Wong A, Mokhtar S, Rasool A
    Images Paediatr Cardiol, 2006 Jan;8(1):1-4.
    PMID: 22368658
    Anomalous origin of the right pulmonary artery is a rare form of congenital heart disease. It usually presents in early infancy with heart failure and rapid development of pulmonary hypertension. There are about 131 cases reported in the literature and we report one such case.
  2. Ibrahim NNIN, Rasool AHG
    Skin Res Technol, 2017 Aug;23(3):321-325.
    PMID: 27868242 DOI: 10.1111/srt.12338
    BACKGROUND: Pulse wave analysis (PWA) and laser Doppler fluximetry (LDF) are non-invasive methods of assessing macrovascular endothelial function and microvascular reactivity respectively. The aim of this study was to assess the correlation between macrovascular endothelial function assessed by PWA and microvascular reactivity assessed by LDF.

    METHOD: 297 healthy and non-smoking subjects (159 females, mean age (±SD) 23.56 ± 4.54 years) underwent microvascular reactivity assessment using LDF followed by macrovascular endothelial function assessments using PWA.

    RESULTS: Pearson's correlation showed no correlation between macrovascular endothelial function and microvascular reactivity (r = -0.10, P = 0.12).

    CONCLUSION: There was no significant correlation between macrovascular endothelial function assessed by PWA and microvascular reactivity assessed by LDF in healthy subjects.

  3. Azemi AK, Mokhtar SS, Rasool AHG
    Oxid Med Cell Longev, 2020;2020:7572892.
    PMID: 32879653 DOI: 10.1155/2020/7572892
    Diabetes mellitus is associated with endothelial dysfunction; it causes progressive vascular damage resulting from an impaired endothelium-dependent vasorelaxation. In the diabetes state, presence of hyperglycemia and insulin resistance predisposes to endothelial dysfunction. Clinacanthus nutans, widely used as a traditional medicine for diabetes is reported to have hypoglycemic, hypolipidemic, antioxidant, and anti-inflammatory properties. However, the possibility of C. nutans affecting the vascular endothelial function in diabetes remains unclear. This study was aimed at evaluating the effects of C. nutans methanolic leaves extract (CNME) on endothelial function in a type 2 diabetes (T2DM) rat model. Sixty male Sprague-Dawley rats were divided into five groups (n = 12 per group): nondiabetic control, nondiabetic treated with four weeks of CNME (500 mg/kg/daily), untreated diabetic rats, diabetic treated with metformin (300 mg/kg/daily), and diabetic treated with CNME (500 mg/kg/daily). T2DM was induced by a single intraperitoneal injection of low-dose streptozotocin (STZ) to rats fed with high-fat diet (HFD). Endothelial-dependent and endothelial-independent relaxations and contractions of the thoracic aorta were determined using the organ bath. Aortic endothelial nitric oxide synthase (eNOS) expression was determined using Western blotting. Endothelial-dependent relaxation was reduced in diabetic rats. Both diabetic groups treated with CNME or metformin significantly improved the impairment in endothelium-dependent vasorelaxation; this was associated with increased expression of aortic eNOS protein. CNME- and metformin-treated groups also reduced aortic endothelium-dependent and aortic endothelium-independent contractions in diabetics. Both of these diabetic-treated groups also reduced blood glucose levels and increased body weight compared to the untreated diabetic group. In conclusion, C. nutans improves endothelial-dependent vasodilatation and reduces endothelial-dependent contraction, thus ameliorating endothelial dysfunction in diabetic rats. This may occur due to its effect on increasing eNOS protein expression.
  4. Azemi AK, Mokhtar SS, Sharif SET, Rasool AHG
    Pharm Biol, 2021 Dec;59(1):1432-1440.
    PMID: 34693870 DOI: 10.1080/13880209.2021.1990357
    CONTEXT: Atherosclerosis predisposes individuals to adverse cardiovascular events. Clinacanthus nutans L. (Acanthaceae) is a traditional remedy used for diabetes and inflammatory conditions.

    OBJECTIVES: To investigate the anti-atherosclerotic activity of a C. nutans leaf methanol extract (CNME) in a type 2 diabetic (T2D) rat model induced by a high-fat diet (HFD) and low-dose streptozotocin.

    MATERIALS AND METHODS: Sixty male Sprague-Dawley rats were divided into five groups: non-diabetic fed a standard diet (C), C + CNME (500 mg/kg, orally), diabetic fed an HFD (DM), DM + CNME (500 mg/kg), and DM + Metformin (DM + Met; 300 mg/kg). Treatment with oral CNME and metformin was administered for 4 weeks. Fasting blood glucose (FBG), serum lipid profile, atherogenic index (AI), aortic tissue superoxide dismutase levels (SOD), malondialdehyde (MDA), and tumour necrosis factor-alpha (TNF-α) were measured. The rats' aortas were stained for histological analysis and intima-media thickness (IMT), a marker of subclinical atherosclerosis.

    RESULTS: The CNME-treated diabetic rats had reduced serum total cholesterol (43.74%; p = 0.0031), triglycerides (80.91%; p = 0.0003), low-density lipoprotein cholesterol (56.64%; p = 0.0008), AI (51.32%; p 

  5. Lee WC, Mokhtar SS, Munisamy S, Yahaya S, Rasool AHG
    Cell Mol Biol (Noisy-le-grand), 2018 May 30;64(7):60-69.
    PMID: 29974854
    Diabetes mellitus is an epidemic that is gaining global concern. Chronic hyperglycemia in diabetes induces the excess production of free radicals. The deleterious effects of excess free radicals are encountered by endogenous antioxidant defense system. Imbalance between free radicals production and antioxidants defense mechanisms leads to a condition known as "oxidative stress". Diabetes mellitus is associated with augmented oxidative stress that induced micro- and macrovascular complications, which presents a significant risk for cardiovascular events. Low vitamin D levels in the body have also been reported to be associated with the pathogenesis of diabetes and enhanced oxidative stress. The article is to review available literature and summarize the relationship between oxidative stress and vitamin D levels in diabetes. We also review the effects of vitamin D analogs supplementation in improving oxidative stress in diabetics.
  6. Azemi AK, Mokhtar SS, Hou LJ, Sharif SET, Rasool AHG
    Biotech Histochem, 2021 Oct;96(7):498-506.
    PMID: 32957845 DOI: 10.1080/10520295.2020.1823480
    We used a type 2 diabetes rat model produced by a high fat diet (HFD) followed by low dose streptozotocin (STZ) to study diabetic vasculopathy. Animals were evaluated for early vascular structural changes, endothelial function, inflammation, lipid profile and oxidative stress. We used 20 male Sprague-Dawley rats divided equally into control and diabetic groups. Diabetic rats were fed an HFD for 4 weeks, injected intraperitoneally with STZ, then sacrificed at week 15. Aortic endothelial nitric oxide synthase (eNOS), aortic superoxide dismutase (SOD), endothelial-dependent and independent relaxation and contraction, intima-media thickness (IMT), malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) were measured. Histopathological characteristics also were assessed. Diabetic rats exhibited higher fasting blood glucose (FBG), low density lipoprotein, total cholesterol and triglycerides compared to the control group. Aortic endothelium-dependent relaxation due to acetylcholine (ACh) was lower, while aortic endothelium-dependent contraction due to calcium ionophore and endothelium-independent contraction due to phenylephrine (PE) were higher for the diabetic group. eNOS expression was lower in the diabetic group compared to controls. IMT and MDA levels were increased, while SOD activity was decreased in the diabetic group compared to controls. TNF-α was higher in the diabetic group than for controls. Our type 2 diabetes model exhibited endothelial dysfunction associated with early vascular structural changes, dyslipidemia, increased vascular oxidative stress, and inflammation. Therefore, the model is suitable for studying diabetic atherosclerosis.
  7. Rahman A, Munisamy S, Ghaffar NA, Mahmood NZ, Rasool AHG
    Microcirculation, 2019 01;26(1):e12513.
    PMID: 30422359 DOI: 10.1111/micc.12513
    OBJECTIVES: To assess microvascular reactivity and glycemic parameters in GDM compared to age and GA matched controls.

    METHODS: This study involved 21 GDM patients and 31 controls. Microvascular reactivity was assessed using LDF and PORH. Microvascular parameters; PORHmax , PORHpeak , and time to peak perfusion (Tp) were recorded after the release of 3 minutes' upper arm occlusion. HOMA-IR was performed to evaluate insulin resistance.

    RESULTS: Average age and GA for subjects were 32.9 years and 29.2 weeks. Mean FBG and a 2-hour postprandial for GDM and controls were 4.87 ± 0.71 vs 3.99 ± 0.59 mmol/L; P 

  8. Ch'ng TW, Chua CY, Ummi Kalsom MA, Azhany Y, Gong V, Rasool A, et al.
    J Curr Glaucoma Pract, 2021 11 2;15(2):78-85.
    PMID: 34720497 DOI: 10.5005/jp-journals-10078-1305
    Aim and objective: To establish the association between 12-month inter-visits ocular perfusion pressure (OPP) and severity of glaucoma.

    Materials and methods: A total of 164 eyes (60 primary open-angle glaucoma, 52 normal-tension glaucoma, and 52 primary angle-closure glaucoma) of 164 patients were analyzed in this prospective cohort study. Patients who demonstrated good compliance to treatment were recruited. The severity of glaucoma was stratified according to the Advanced Glaucoma Intervention Study (AGIS) score based on reliable and reproducible visual field analysis at baseline. OPP was obtained at baseline and a 3-monthly follow-up visit over a 12-month duration. The pattern and fluctuation of mean OPP were studied. Repetitive measure ANOVA and one-way ANOVA were used for statistical analysis.

    Results: The inter-visits mean OPP (p = 0.010), systolic OPP (p = 0.020), diastolic OPP (p = 0.010), systolic blood pressure (p = 0.040), and diastolic blood pressure (p = 0.006) showed significant difference with severity of glaucoma. There was no significant difference between mean inter-visits intraocular pressure (IOP) and severity of glaucoma (p = 0.410). The end-stage glaucoma group had the lowest mean OPP and widest inter-visit mean OPP fluctuation. Early and mild glaucoma patients demonstrated higher mean OPP compared with moderate, severe, and end-stage glaucoma.

    Conclusion: There is a significant association between OPP and the severity of glaucoma. Balancing blood pressure and IOP is important in optimizing adequate perfusion and prevent further damage to the optic nerve head.

    How to cite this article: Ch'ng TW, Chua CY, Ummi Kalsom MA, et al. Ocular Perfusion Pressure and Severity of Glaucoma: Is There a Link? J Curr Glaucoma Pract 2021;15(2):78-85.

  9. Wee CL, Azemi AK, Mokhtar SS, Yahaya S, Yaacob NS, Rasool AHG
    Microvasc Res, 2023 Nov;150:104574.
    PMID: 37390963 DOI: 10.1016/j.mvr.2023.104574
    Low vitamin D (vitD) levels have been reported to be a risk factor for diabetes-related cardiovascular complications. This study examined the effects of vitD deficiency on oxidative stress (OS), inflammation, and levels of the vasoconstrictor angiotensin II (Ang II) in the microvascular tissue of type 2 diabetic patients. Patients were categorized into (i) vitD non-deficient diabetics (DNP, n = 10) and (ii) vitD-deficient diabetics (DDP, n = 10), based on their serum 25(OH)D levels. Subcutaneous fat tissues with intact blood vessels were collected during lower limb surgical procedures. The blood vessel were isolated; measurements of the antioxidant enzyme superoxide dismutase (SOD) activity, OS marker malondialdehyde (MDA), Ang II, and the inflammatory marker, TNF-α of the microvascular tissues were determined. Elevated MDA levels and reduced SOD activity, with higher levels of TNF-α and Ang II were observed in the microvascular tissues of DDP compared to DNP. VitD deficiency did not associate with glycemic parameters (fasting blood glucose and glycated hemoglobin) levels. In conclusion, vitD deficiency was correlated with higher microvascular tissue OS, inflammation, and Ang II levels in type 2 diabetic patients. This may contribute to early vasculopathy that occurs in diabetic patients, thus, may contribute to the planning of therapeutic strategies to delay or prevent cardiovascular complications.
  10. Wee CL, Mokhtar SS, Banga Singh KK, Rasool AHG
    Microvasc Res, 2021 Nov;138:104227.
    PMID: 34324883 DOI: 10.1016/j.mvr.2021.104227
    This study examined the effects of vitamin D deficiency on vascular function and tissue oxidative status in the microcirculation; and whether or not these effects can be ameliorated with calcitriol, the active vitamin D metabolite. Three groups (n = 10 each) of male Sprague Dawley rats were fed for 10 weeks with control diet (CR), vitamin D-deficient diet without (DR), or with oral calcitriol supplementation (0.15 μg/kg) for the last four weeks (DSR). After 10 weeks, rats were sacrificed; mesenteric arterial rings were studied using wire myograph. Oxidative stress biomarkers malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity were measured in the mesenteric arterial tissue. Vascular protein expression of endothelial nitric oxide synthase (eNOS) was determined by Western blotting. Acetylcholine-induced endothelium-dependent relaxation of DR was lower than CR. eNOS expression and SOD activity were lower in mesenteric arterial tissue of DR compared to CR. Calcitriol supplementation to DSR did not ameliorate the above parameters; in fact, augmented endothelium-dependent contraction was observed. Serum calcium was higher in DSR compared to CR and DR. In conclusion, vitamin D deficiency impaired microvascular vasodilation, associated with eNOS downregulation and reduced antioxidant activity. Calcitriol supplementation to vitamin D-deficient rats at the dosage used augmented endothelium-dependent contraction, possibly due to hypercalcaemia.
  11. Wee CL, Mokhtar SS, Singh KKB, Yahaya S, Leung SWS, Rasool AHG
    Oxid Med Cell Longev, 2021;2021:3109294.
    PMID: 33623633 DOI: 10.1155/2021/3109294
    Diabetes mellitus contributes to macro- and microvascular complications, leading to adverse cardiovascular events. This study examined the effects of vitamin D deficiency on the vascular function and tissue oxidative status in the microcirculation of diabetic rats and to determine whether these effects can be reversed with calcitriol (active vitamin D metabolite) supplementation. Streptozotocin-induced diabetic rats were fed for 10 weeks with control diet (DC) or vitamin D-deficient diet without (DD) or with oral calcitriol supplementation (0.15 μg/kg) in the last four weeks (DDS) (10 rats each group). A nondiabetic rat group that received control diet was also included (NR). After 10 weeks, rats were sacrificed; mesenteric arterial rings with and without endothelium were studied using wire myograph. Western blotting of the mesenteric arterial tissue was performed to determine the protein expression of endothelial nitric oxide synthase (eNOS) enzyme. Antioxidant enzyme superoxide dismutase (SOD) activity and oxidative stress marker malondialdehyde (MDA) levels in the mesenteric arterial tissue were also measured. The DC group had significantly lower acetylcholine-induced relaxation and augmented endothelium-dependent contraction, with reduced eNOS expression, compared to NR rats. In mesenteric arteries of DD, acetylcholine-induced endothelium-dependent and sodium nitroprusside-induced endothelium-independent relaxations were lower than those in DC. Calcitriol supplementation in DDS restored endothelium-dependent relaxation. Mesenteric artery endothelium-dependent contraction of DD was greater than DC; it was not affected by calcitriol supplementation. The eNOS protein expression and SOD activity were significantly lower while MDA levels were greater in DD compared to DC; these effects were not observed in DDS that received calcitriol supplementation. In conclusion, vitamin D deficiency causes eNOS downregulation and oxidative stress, thereby impairing the vascular function and posing an additional risk for microvascular complications in diabetes. Calcitriol supplementation to diabetics with vitamin D deficiency could potentially be useful in the management of or as an adjunct to diabetes-related cardiovascular complications.
  12. Zainudin AM, Rasool AHG, Yaacob NM, Muhamad R, Mohamed WMIW
    BMC Endocr Disord, 2024 Jul 18;24(1):118.
    PMID: 39020348 DOI: 10.1186/s12902-024-01577-6
    BACKGROUND: Many patients with T2DM on insulin are not optimally controlled despite receiving standard diabetes education counselling. Poor insulin adherence may be a contributing factor. We developed and evaluated a new module [Universiti Sains Malaysia-Insulin Adherence Module (USM-IAM)] on insulin-treated patients with poorly controlled diabetes.

    METHODS: Eligibility criteria are those diagnosed with T2DM, aged between 18 and 65 years, with HbA1c between 8 and 15% and on insulin therapy for 1 year. Patients were randomly allocated to receive either the USM-IAM-based counselling or the standard counselling (SC) at baseline and the second visit. Patients were instructed to adjust insulin doses based on blood glucose levels. Outcomes were changes in adherence score, FBS and HbA1c levels from baseline to 3 months and baseline to sixth month.

    RESULTS: Ninety patients were randomised to each group. The baseline sociodemographic and clinical characteristics were homogenous among groups. Ninety patients were analysed for each group. Adherence score changes between baseline to 3 months were - 8.30 (- 11.47, - 5.14) in USM-IAM-based counselling group (USM-IAM) and - 7.64 (- 10.89, - 4.40) in standard counselling group (SCG), between baseline to sixth month were - 10.21 (- 13.40, - 7.03) in USM-IAM and - 10.79 (- 14.64, - 6.97) in SCG. FBS changes between baseline to 3 months were 1.374 (0.25, 2.50) in USM-IAM and 0.438 (- 0.66, 1.54) in SCG, and between baseline to sixth month were 1.713 (0.473, 2.95) in USM-IAM and 0.998 (- 0.02, 2.01) in SCG. HbA1c changes between baseline to 3 months were 1.374 (0.25, 2.50) in USM-IAM and 0.547 (0.12, 0.98) in SCG, and between baseline to sixth month were 1.03 (0.65, 1.41) in USM-IAM and 0.617 (0.20, 1.03) in SCG. Between-subjects effects for all outcomes were not statistically significant.

    CONCLUSION: Both groups had significant improvements in adherence score and HbA1c with time, with higher improvement in patients receiving the USM-IAM. FBS reductions were significant in the intervention group but not in the control group.

    TRIAL REGISTRATION: This study protocol is registered with Clicaltrials.gov with ID NCT05125185 dated 17th November 2021.

  13. Ibrahim NNIN, Rasool AHG, Rahman RA, Azlan M, Aziz AA
    Microvasc Res, 2024 Nov 23.
    PMID: 39586372 DOI: 10.1016/j.mvr.2024.104772
    BACKGROUND: Pulse wave analysis (PWA) assesses endothelial dependent vasodilation (EDV) via the change in augmentation index (AIx) and has been used as a tool to assess endothelial function. However, its effectiveness in assessing the response to lipid lowering treatment has not been evaluated. The study aimed to describe and correlate the change in EDV following lipid lowering intervention in patients with hypercholesterolemia.

    METHODS: 48 newly diagnosed patients with hypercholesterolemia underwent 6 months intervention with statin and/or therapeutic lifestyle changes (TLC) in clinical setting. Lipid profile measurement and endothelial function assessment using PWA were performed pre- and post-intervention.

    RESULTS: Significant reductions in low density lipoprotein cholesterol (LDL-C), non-high density lipoprotein cholesterol (non-HDL-C) and total cholesterol (TC) with corresponding significant improvement in EDV (2.94 ± 3.69 % to 7.50 ± 3.79 %, p 

  14. Al-Tahami BAM, Al-Safi Ismail AA, Sanip Z, Yusoff Z, Shihabudin TMT, Singh TSP, et al.
    J Nippon Med Sch, 2017;84(3):125-132.
    PMID: 28724846 DOI: 10.1272/jnms.84.125
    INTRODUCTION: Obesity is associated with numerous health problems, particularly metabolic and cardiovascular complications. This study aimed to assess the effects that, nine months of pharmacological intervention with orlistat or sibutramine, on obese Malaysians' body weight and compositions, metabolic profiles and inflammatory marker.

    METHODS: Seventy-six obese subjects were randomly placed into two groups. The first group received three daily 120 mg dosages of orlistat for nine months (n=39), and the second group received a once daily 10 or 15 mg dosage of sibutramine for nine months (n=37). Baseline measurements for weight, body mass index (BMI), waist circumference (WC), body fat percentage (BF), visceral fat (VF), adiponectin, fasting plasma glucose (FPG), fasting insulin, pancreatic B cell secretory capacity (HOMA%B), insulin sensitivity (HOMA%S), insulin resistance (HOMA-IR) and serum high sensitivity C-reactive protein (hs-CRP) were performed and repeated during the sixth and ninth months of treatment.

    RESULTS: Twenty-four subjects completed the trial in both groups. For both groups, weight, BMI, WC, BF, VF, HOMA-IR and hs-CRP were significantly lower at the end of the nine month intervention. However, there were no significant differences between the two groups for these parameters with nine months treatment. There was a significant decrease in FPG in orlistat group; while fasting insulin and HOMA%B reduced in sibutramine group. For both groups, there were also significant increases in adiponectin levels and HOMA%S at the end of the nine month intervention.

    CONCLUSION: Nine months of treatment with orlistat and sibutramine not only reduced weight but also significantly improved BMI, WC, BF, VF, FPG, adiponectin, fasting insulin, HOMA%B, HOMA%S, HOMA-IR and hs-CRP. These improvements could prove useful in the reduction of metabolic and cardiovascular risks in obese subjects.

  15. Siti Hajar MH, Zulkefli S, Juwita S, Norhayati MN, Siti Suhaila MY, Rasool AHG, et al.
    PeerJ, 2018;6:e5758.
    PMID: 30356972 DOI: 10.7717/peerj.5758
    Background: Secondhand smoke (SHS) exposure has adverse effects on the cardiovascular system. This study aimed to determine the effects of SHS on the cardiovascular disease biomarkers, namely the metabolic, inflammatory, and oxidative stress markers in healthy adult women.

    Methods: This comparative cross-sectional study was conducted among healthy women. The cases included those women exposed to SHS, and the controls included those women not exposed to SHS. SHS exposure was defined as being exposed to SHS for at least 15 min for 2 days per week. Venous blood was taken to measure the metabolic markers (high molecular weight adiponectin, insulin level, insulin resistance, and nonesterified fatty acids), oxidative stress markers (oxidized low density lipoprotein cholesterol and 8-isoprostane), and inflammatory markers (high-sensitivity C-reactive protein and interleukin-6). A hair nicotine analysis was also performed. An analysis of covariance and a simple linear regression analysis were conducted.

    Results: There were 101 women in the SHS exposure group and 91 women in the non-SHS exposure group. The mean (with standard deviation) of the hair nicotine levels was significantly higher in the SHS exposure group when compared to the non-SHS exposure group [0.22 (0.62) vs. 0.04 (0.11) ng/mg; P = 0.009]. No significant differences were observed in the high molecular weight adiponectin, insulin and insulin resistance, nonesterified fatty acids, 8-isoprostane, oxidized low density lipoprotein cholesterol, interleukin-6, and high-sensitivity C-reactive protein between the two groups. The serum high molecular weight adiponectin was negatively associated with the insulin level and insulin resistance in the women exposed to SHS. However, no significant relationships were seen between the high molecular weight adiponectin and nonesterified fatty acids, 8-isoprostane, oxidized low density lipoprotein cholesterol, high-sensitivity C-reactive protein in the SHS group.

    Discussion: There were no significant differences in the metabolic, oxidative stress, and inflammatory markers between the SHS exposure and non-SHS exposure healthy women. A low serum level of high molecular weight adiponectin was associated with an increased insulin level and resistance in the women exposed to SHS.

  16. Mustapha S, Mohammed M, Azemi AK, Yunusa I, Shehu A, Mustapha L, et al.
    Oxid Med Cell Longev, 2021;2021:8830880.
    PMID: 33995826 DOI: 10.1155/2021/8830880
    The role of the endoplasmic reticulum (ER) has evolved from protein synthesis, processing, and other secretory pathways to forming a foundation for lipid biosynthesis and other metabolic functions. Maintaining ER homeostasis is essential for normal cellular function and survival. An imbalance in the ER implied stressful conditions such as metabolic distress, which activates a protective process called unfolded protein response (UPR). This response is activated through some canonical branches of ER stress, i.e., the protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1α (IRE1α), and activating transcription factor 6 (ATF6). Therefore, chronic hyperglycemia, hyperinsulinemia, increased proinflammatory cytokines, and free fatty acids (FFAs) found in diabesity (a pathophysiological link between obesity and diabetes) could lead to ER stress. However, limited data exist regarding ER stress and its association with diabesity, particularly the implicated proteins and molecular mechanisms. Thus, this review highlights the role of ER stress in relation to some proteins involved in diabesity pathogenesis and provides insight into possible pathways that could serve as novel targets for therapeutic intervention.
  17. 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.
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