Displaying publications 21 - 40 of 81 in total

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  1. Hasan MM, Ahmed QU, Mat Soad SZ, Tunna TS
    Biomed Pharmacother, 2018 May;101:833-841.
    PMID: 29635892 DOI: 10.1016/j.biopha.2018.02.137
    Diabetes mellitus is a chronic disease which has high prevalence. The deficiency in insulin production or impaired insulin function is the underlying cause of this disease. Utilization of plant sources as a cure of diabetes has rich evidence in the history. Recently, the traditional medicinal plants have been investigated scientifically to understand the underlying mechanism behind antidiabetic potential. In this regard, a substantial number of in vivo and in vitro models have been introduced for investigating the bottom-line mechanism of the antidiabetic effect. A good number of methods have been reported to be used successfully to determine antidiabetic effects of plant extracts or isolated compounds. This review encompasses all the possible methods with a list of medicinal plants which may contribute to discovering a novel drug to treat diabetes more efficaciously with the minimum or no side effects.
    Matched MeSH terms: Insulin/metabolism
  2. Asghar A, Firasat S, Afshan K, Naz S
    Mol Biol Rep, 2023 Jan;50(1):57-64.
    PMID: 36301463 DOI: 10.1007/s11033-022-08011-x
    BACKGROUND: CDK5 regulatory subunit associated protein 1 like 1 (CDKAL1) encodes a tRNA modifying enzyme involved in the proper protein translation and regulation of insulin production encoded by the CDKL gene. Sequence variations in the CDKAL1 gene lead to the misreading of the Lys codon in proinsulin, resulting in decreased glucose-stimulated proinsulin production. Various polymorphic sequence variants of the CDKAL1 gene such as rs7754840, rs7756992, rs9465871, and rs10946398 are reported to be associated with type 2 diabetes mellitus and gestational diabetes mellitus (GDM) incidence. One of these single nucleotide polymorphisms i.e., rs10946398 has been reported to impact the risk of GDM and its outcomes in pregnant women of different ethnicities i.e., Egypt, Chinese, Korean, Indian, Arab, and Malaysian. Numerous findings have shown that rs10946398 overturns the regulation of CDKAL1 expression, resulting in decreased insulin production and elevated risk of GDM. However, there is no data regarding rs10946398 genotype association with GDM incidence in our population.

    METHODOLOGY: In this study, 47 GDM patients and 40 age-matched controls were genotyped for rs10946398 CDKAL1 variant using Tetra primer Amplification Refractory Mutation System Polymerase Chain Reaction (Tetra ARMS-PCR).

    RESULTS: Analysis of the results showed the significant association of the C allele of CDKAL1 SNP rs10946398 (χ2 = 0.02 p = 0.001) with the risk of GDM development. Conclusively, the results support the role of SNP i.e., rs10946398 of CDKAL1 gene in GDM development in Pakistani female patients. However, future large-scale studies are needed to functionally authenticate the role of variant genotypes in the disease pathogenesis and progression.

    Matched MeSH terms: Insulin/metabolism
  3. Aamir K, Sethi G, Afrin MR, Hossain CF, Jusuf PR, Sarker SD, et al.
    Life Sci, 2023 Aug 15;327:121856.
    PMID: 37307966 DOI: 10.1016/j.lfs.2023.121856
    BACKGROUND: Arjunolic acid (AA) is a potent phytochemical with multiple therapeutics effects. In this study, AA is evaluated on type 2 diabetic (T2DM) rats to understand the mechanism of β-cell linkage with Toll-like receptor 4 (TLR-4) and canonical Wnt signaling. However, its role in modulating TLR-4 and canonical Wnt/β-catenin crosstalk on insulin signaling remains unclear during T2DM. Aim The current study is aimed to examine the potential role of AA on insulin signaling and TLR-4-Wnt crosstalk in the pancreas of type 2 diabetic rats.

    METHOD: Multiple methods were used to determine molecular cognizance of AA in T2DM rats, when treated with different dosage levels. Histopathological and histomorphometry analysis was conducted using masson trichrome and H&E stains. While, protein and mRNA expressions of TLR-4/Wnt and insulin signaling were assessed using automated Western blotting (jess), immunohistochemistry, and RT-PCR.

    RESULTS: Histopathological findings revealed that AA had reversed back the T2DM-induced apoptosis and necrosis caused to rats pancreas. Molecular findings exhibited prominent effects of AA in downregulating the elevated level of TLR-4, MyD88, NF-κB, p-JNK, and Wnt/β-catenin by blocking TLR-4/MyD88 and canonical Wnt signaling in diabetic pancreas, while IRS-1, PI3K, and pAkt were all upregulated by altering the NF-κB and β-catenin crosstalk during T2DM.

    CONCLUSION: Overall results, indicate that AA has potential to develop as an effective therapeutic in the treatment of T2DM associated meta-inflammation. However, future preclinical research at multiple dose level in a long-term chronic T2DM disease model is warranted to understand its clinical relevance in cardiometabolic disease.

    Matched MeSH terms: Insulin/metabolism
  4. Subramaniam S, Ong KC, Sabaratnam V, Chua KH, Kuppusamy UR
    Int J Med Mushrooms, 2023;25(4):27-42.
    PMID: 37075082 DOI: 10.1615/IntJMedMushrooms.2023047595
    Ganoderma neo-japonicum Imazeki is a medicinal mushroom consumed by the indigenous people in Malaysia as a remedy for diabetes. This study aims to validate the efficacy of G. neo-japonicum polysaccharides (GNJP) on obesity-induced type 2 diabetes mellitus (T2DM) in C57BL/6J mice. Mice were divided into seven groups; normal diet (ND)-control, high-fat-diet (HFD)-control, HFDGNJP-treated (50, 100, 200 mg/kg b.w.), HFDMET (metformin 50 mg/kg; positive-control) and ND-GNJP (200 mg/kg b.w.). Mice were administered GNJP or metformin orally for 10 weeks (thrice/week) and sacrificed after an oral glucose tolerance test. Body weight, serum biochemicals, liver histology, adipocyte gene expressions, glucose and insulin levels were measured. HFD caused obesity, dyslipidemia, and diabetes in the untreated groups. GNJP (50 mg/kg b.w.) supplementation prevented weight gain and liver steatosis, improved serum lipid profile and glucose tolerance and attenuated hyperglycemia and hyperinsulinemia more effectively when compared with the other treatment groups. The prevention of obesity and lipid dysregulation is plausibly attributed to the increased hormone-sensitive lipase and reduced Akt-1 and Ppary gene expressions while the up-regulation of AdipoQ (adiponectin), Prkag2 and Slc2a4 genes served to sensitize insulin and improve glucose uptake. Thus, supplementation with an appropriate dose of GNJP has promising efficacies in preventing HFD aka obesity-induced T2DM and associated metabolic abnormalities.
    Matched MeSH terms: Insulin/metabolism
  5. Govindasamy V, Ronald VS, Abdullah AN, Nathan KR, Ab Aziz ZA, Abdullah M, et al.
    J Dent Res, 2011 May;90(5):646-52.
    PMID: 21335539 DOI: 10.1177/0022034510396879
    The post-natal dental pulp tissue contains a population of multipotent mesenchymal progenitor cells known as dental pulp stromal/stem cells (DPSCs), with high proliferative potential for self-renewal. In this investigation, we explored the potential of DPSCs to differentiate into pancreatic cell lineage resembling islet-like cell aggregates (ICAs). We isolated, propagated, and characterized DPSCs and demonstrated that these could be differentiated into adipogenic, chondrogenic, and osteogenic lineage upon exposure to an appropriate cocktail of differentiating agents. Using a three-step protocol reported previously by our group, we succeeded in obtaining ICAs from DPSCs. The identity of ICAs was confirmed as islets by dithiozone-positive staining, as well as by expression of C-peptide, Pdx-1, Pax4, Pax6, Ngn3, and Isl-1. There were several-fold up-regulations of these transcription factors proportional to days of differentiation as compared with undifferentiated DPSCs. Day 10 ICAs released insulin and C-peptide in a glucose-dependent manner, exhibiting in vitro functionality. Our results demonstrated for the first time that DPSCs could be differentiated into pancreatic cell lineage and offer an unconventional and non-controversial source of human tissue that could be used for autologous stem cell therapy in diabetes.
    Matched MeSH terms: Insulin/metabolism
  6. Budiman C, Goh CKW, Arief II, Yusuf M
    Cell Stress Chaperones, 2021 Mar;26(2):377-386.
    PMID: 33247372 DOI: 10.1007/s12192-020-01183-0
    FKBP22 of a psychrophilic bacterium, Shewanella sp. SIB1 (SIB1 FKBP22), is a member of peptidyl-prolyl cis-trans isomerase (PPIase) and consists of N- and C-domains responsible for chaperone-like and PPIase catalytic activities, respectively. The chaperone-like activity of SIB1 FKBP22 was previously evidenced by its ability to prevent dithiothreitol (DTT)-induced insulin aggregation. Nevertheless, the mechanism by which this protein inhibits the aggregation remains unclear. To address this, the binding affinity of SIB1 FKBP22 to the native or reduced states of insulin was examined using surface plasmon resonance (SPR). The native and reduced states refer to insulin in the absence or DTT presence, respectively. The SPR sensorgram showed that SIB1 FKBP22 binds specifically to the reduced state of insulin, with a KD value of 37.31 ± 3.20 μM. This binding was facilitated by the N-domain, as indicated by the comparable KD values of the N-domain and SIB1 FKBP22. Meanwhile, the reduced state of insulin was found to have no affinity towards the C-domain. The KD value of SIB1 FKBP22 was slightly decreased by NaCl but was not severely affected by FK506, a specific FKBP inhibitor. Similarly, the prevention of DTT-induced aggregation by SIB1 FKBP22 was also modulated by the N-domain and was not affected by FK506. Further, the reduced and native states of insulin had no effect on the catalytic efficiency (kcat/KM) of SIB1 FKBP22 towards a peptide substrate. Nevertheless, the reduced state of insulin slightly reduced the catalytic efficiency towards refolding RNase T1, at up to 1.5-fold lower than in the absence of insulin. These results suggested that the binding event was mainly facilitated by hydrophobic interaction and was independent from its PPIase activity. Altogether, a possible mechanism by which SIB1 FKBP22 prevents DTT-induced insulin aggregation was proposed.
    Matched MeSH terms: Insulin/metabolism*
  7. Sarmadi B, Aminuddin F, Hamid M, Saari N, Abdul-Hamid A, Ismail A
    Food Chem, 2012 Sep 15;134(2):905-11.
    PMID: 23107706 DOI: 10.1016/j.foodchem.2012.02.202
    Fat, alkaloid and polyphenol contents of two clones of cocoa (UIT1 and PBC 140) were removed and the remaining powder was autolyzed at pH 3.5 and 5.2. Based on the results, autolysates of UIT produced at pH 3.5 exhibited the highest ability to inhibit α-amylase activity. However, no α-glucosidase inhibition activity was observed under the conditions specified. Autolysates produced under pH 3.5 caused the highest amount of insulin secretion. In streptozotocin-diabetic rats, all cocoa autolysates significantly decreased blood glucose at 4h. To assure that the results from the assays were not due to the polyphenols of cocoa autolysates qualitative and quantitative tests were applied. According to their results cocoa autolysates were found to be free from polyphenols. Analysis of amino acid composition revealed that cocoa autolysates were abundant in hydrophobic amino acids. It can be suggested that besides other compounds of cocoa, its peptides and amino acids could contribute to its health benefits.
    Matched MeSH terms: Insulin/metabolism
  8. Hani H, Ibrahim TA, Othman AM, Lila MA, bt Allaudin ZN
    Xenotransplantation, 2010 12 17;17(6):469-80.
    PMID: 21158948 DOI: 10.1111/j.1399-3089.2010.00616.x
    BACKGROUND: Insufficient availability of human donors makes the search for alternative source of islet cells mandatory for future developments in pancreatic transplantation. The present study investigates the potential of caprine as an alternative source of pancreatic islets. The objectives of the study were to optimize techniques for caprine islet isolation and purification for culture establishment, and to subsequently assess their viable and functional potential.

    METHODS: Caprine pancreatic tissues were collected from a local slaughterhouse and prior transported to the laboratory by maintaining the cold chain. Islets were obtained by a collagenase-based digestion and optimized isolation technique. Islet cell purity and viability were determined by dithizone and trypan blue staining, respectively. Islet clusters of different sizes were positively identified by staining methods and demonstrated 90% viability in the culture system. Following static incubation, an in vitro insulin secretion assay was carried out and analyzed by ELISA.

    RESULTS: The islets remained satisfactorily viable for 5 days in the culture system following regular media changes. The current study has successfully optimized the isolation, purification and culture maintenance of caprine islets.

    CONCLUSION: The successful yield, viability and functionality of islets isolated from the optimized protocol provide promising potential as an alternative source of islets for diabetes and transplantation researches.

    Matched MeSH terms: Insulin/metabolism
  9. Haghvirdizadeh P, Mohamed Z, Abdullah NA, Haghvirdizadeh P, Haerian MS, Haerian BS
    J Diabetes Res, 2015;2015:908152.
    PMID: 26448950 DOI: 10.1155/2015/908152
    Diabetes mellitus (DM) is a major worldwide health problem and its prevalence has been rapidly increasing in the last century. It is caused by defects in insulin secretion or insulin action or both, leading to hyperglycemia. Of the various types of DM, type 2 occurs most frequently. Multiple genes and their interactions are involved in the insulin secretion pathway. Insulin secretion is mediated through the ATP-sensitive potassium (KATP) channel in pancreatic beta cells. This channel is a heteromeric protein, composed of four inward-rectifier potassium ion channel (Kir6.2) tetramers, which form the pore of the KATP channel, as well as sulfonylurea receptor 1 subunits surrounding the pore. Kir6.2 is encoded by the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene, a member of the potassium channel genes. Numerous studies have reported the involvement of single nucleotide polymorphisms of the KCNJ11 gene and their interactions in the susceptibility to DM. This review discusses the current evidence for the contribution of common KCNJ11 genetic variants to the development of DM. Future studies should concentrate on understanding the exact role played by these risk variants in the development of DM.
    Matched MeSH terms: Insulin/metabolism
  10. Mohamad M, Mitchell SJ, Wu LE, White MY, Cordwell SJ, Mach J, et al.
    Aging Cell, 2016 08;15(4):706-15.
    PMID: 27095270 DOI: 10.1111/acel.12481
    While age-related insulin resistance and hyperinsulinemia are usually considered to be secondary to changes in muscle, the liver also plays a key role in whole-body insulin handling and its role in age-related changes in insulin homeostasis is largely unknown. Here, we show that patent pores called 'fenestrations' are essential for insulin transfer across the liver sinusoidal endothelium and that age-related loss of fenestrations causes an impaired insulin clearance and hyperinsulinemia, induces hepatic insulin resistance, impairs hepatic insulin signaling, and deranges glucose homeostasis. To further define the role of fenestrations in hepatic insulin signaling without any of the long-term adaptive responses that occur with aging, we induced acute defenestration using poloxamer 407 (P407), and this replicated many of the age-related changes in hepatic glucose and insulin handling. Loss of fenestrations in the liver sinusoidal endothelium is a hallmark of aging that has previously been shown to cause deficits in hepatic drug and lipoprotein metabolism and now insulin. Liver defenestration thus provides a new mechanism that potentially contributes to age-related insulin resistance.
    Matched MeSH terms: Insulin/metabolism*
  11. Singh B, Choo KE, Ibrahim J, Johnston W, Davis TM
    Trans R Soc Trop Med Hyg, 1998 12 23;92(5):532-7.
    PMID: 9861371
    To determine whether glucose turnover is increased in acute falciparum malaria compared to enteric fever in children, steady-state 6,6-D2-glucose turnover was measured in 9 Malaysian children with uncomplicated malaria (6 males and 3 females; median age 10 years, body weight 22 kg) and in 12 with uncomplicated enteric fever (8 males and 4 females; median age 10 years, body weight 24 kg) in acute illness, after quinine (5 malaria patients) and in convalescence. Baseline plasma glucose concentrations in malaria and enteric fever were similar (all values are medians [ranges in brackets]) 5.6 [3.2-11.3] vs. 5.5 [4.2-8.0] mmol/L), as were serum insulin levels (5.6 [0.4-26.5] vs. 6.8 [1.1-22.5] milliunits/L; P > 0.4). Glucose turnover in the malaria patients was higher than in patients with enteric fever (6.27 [2.71-6.87] vs. 5.20 [4.50-6.08] mg/kg.min; P = 0.02) and in convalescence (4.74 [3.35-6.79] mg/kg.min; P = 0.05 vs. acute malaria study), and fell after quinine together with a rise in serum insulin (P = 0.03). Basal plasma lactate concentrations were higher in enteric fever than in malaria (3.4 [1.8-6.4] vs. 0.8 [0.3-3.8] mmol/L; P < 0.0001) and correlated inversely with glucose turnover in this group (rs = -0.60; n = 12; P = 0.02). These data suggest that glucose turnover is 20% greater in malaria than in enteric fever. This might reflect increased non-insulin-mediated glucose uptake in falciparum malaria and/or impaired gluconeogenesis in enteric fever, and may have implications for metabolic complications and their clinical management in both infections.
    Matched MeSH terms: Insulin/metabolism
  12. Taib M, Tan LL, Abd Karim NH, Ta GC, Heng LY, Khalid B
    Talanta, 2020 Jan 15;207:120321.
    PMID: 31594568 DOI: 10.1016/j.talanta.2019.120321
    An optical aptasensor-based sensing platform for rapid insulin detection was fabricated. Aminated porous silica microparticles (PSiMPs) were synthesized via a facile mini-emulsion method to provide large surface area for covalent immobilization of insulin-binding DNA aptamer (IGA3) by glutaraldehyde cross-linking protocol. A Nickel-salphen type complex with piperidine side chain [Ni(II)-SP] was synthesized with a simple one-pot reaction, and functionalized as an optical label due to strong π-π interaction between aromatic carbons of G-quadruplex DNA aptamer and planar aromatic groups of Ni(II)-SP to form the immobilized IGA3-Ni(II)-SP complex, i.e. the dye-labeled aptamer, thereby bringing yellow colouration to the immobilized G-quartet plane. Optical characterization of aptasensor towards insulin binding was carried out with a fiber optic reflectance spectrophotometer. The maximum reflectance intensity of the immobilized IGA3-Ni(II)-SP complex at 656 nm decreased upon binding with insulin as aptasensor changed to brownish orange colouration in the background. This allows optical detection of insulin as the colour change of aptasensor is dependent on the insulin concentration. The linear detection range of the aptasensor is obtained from 10 to 50 μIU mL-1 (R2 = 0.9757), which conformed to the normal fasting insulin levels in human with a limit of detection (LOD) at 3.71 μIU mL-1. The aptasensor showed fast response time of 40 min and long shelf life stability of >3 weeks. Insulin detection using healthy human serums with informed consent provided by participants suggests the DNA aptamer biosensor was in good agreement with ELISA standard method using BIOMATIK Human INS (Insulin) ELISA Kit.
    Matched MeSH terms: Insulin/metabolism
  13. Taha H, Arya A, Paydar M, Looi CY, Wong WF, Vasudeva Murthy CR, et al.
    Food Chem Toxicol, 2014 Apr;66:295-306.
    PMID: 24518542 DOI: 10.1016/j.fct.2014.01.054
    The current study aimed to ascertain the antidiabetic potential of Pseuduvaria monticola bark methanolic extract (PMm) using in vitro mechanistic study models. In particular, the study determined the effect of PMm on cellular viability, 2-NBDG glucose uptake, insulin secretion, and NF-κB translocation in mouse pancreatic insulinoma cells (NIT-1). Furthermore, in vivo acute toxicity and antidiabetic studies were performed using streptozotocin (STZ)-induced type 1 and STZ-nicotinamide-induced type 2 diabetic rat models to evaluate various biochemical parameters and markers of oxidative stress and pro-inflammatory cytokines. Five isoquinoline alkaloids and three phenolic compounds were tentatively identified in the PMm by LC/MS Triple TOF. The study results showed that PMm is non-toxic to NIT-1 cells and significantly increased the glucose uptake and insulin secretion without affecting the translocation of NF-κB. Moreover, the non-toxic effects of PMm were confirmed through an in vivo acute toxicity study, which revealed that the serum insulin and C-peptide levels were significantly upregulated in type 2 diabetic rats and that no significant changes were observed in type 1 diabetic rats. Similarly, PMm was found to downregulate the levels of oxidative stress and pro-inflammatory cytokines in type 2 diabetic rats by alleviating hyperglycemia. Therefore, we conclude that PMm may be developed as an antidiabetic agent for the treatment of type 2 diabetes-associated conditions.
    Matched MeSH terms: Insulin/metabolism*
  14. Subramaniam S, Sabaratnam V, Heng CK, Kuppusamy UR
    Int J Med Mushrooms, 2020;22(1):65-78.
    PMID: 32463999 DOI: 10.1615/IntJMedMushrooms.2020033250
    Ganoderma neo-japonicum is an annual polypore mushroom that is consumed by Malaysian indigenous tribes to treat various ailments including diabetes. The present study aimed to investigate the nutritive composition and in vitro antihyperglycemic effects of G. neo-japonicum extracts on 3T3-L1 preadipocytes. Nutritional analysis of G. neo-japonicum basidiocarps indicated a predominant presence of carbohydrates, proteins, dietary fiber, and microelements. Hot aqueous extract (AE) and its isolated (1,3)(1,6)-β-D-glucan polysaccharide (GNJP) from basidiocarps of G. neo-japonicum were evaluated for their ability to stimulate insulin independent adipogenesis, glucose uptake, adiponectin secretion, and regulate gene expression in 3T3-L1 adipocytes. GNJP showed a dose dependent stimulation of glucose uptake and adiponectin secretion but attenuated lipid accumulation in 3T3-L1 adipocytes. It upregulated the expressions of adiponectin, Aktl (protein kinase B), PPARγ (peroxisome proliferator activated receptor gamma), PRKAG2 (protein kinase, AMP activated), and Slc2a4 (glucose transporter) genes to stimulate glucose uptake in 3T3-L1 cells, which may have contributed to the insulin-mimicking activities observed in this study. In summary, the nutritive compositions and significant glucose uptake stimulatory activities of GNJP indicated that it may have potential use in the formulation of functional food for the management of hyperglycemia, insulin resistance, and related complications.
    Matched MeSH terms: Insulin/metabolism*
  15. Nurdiana S, Goh YM, Ahmad H, Dom SM, Syimal'ain Azmi N, Noor Mohamad Zin NS, et al.
    BMC Complement Altern Med, 2017 Jun 02;17(1):290.
    PMID: 28576138 DOI: 10.1186/s12906-017-1762-8
    BACKGROUND: The potential application of Ficus deltoidea and vitexin for the management of symptomatologies associated with diabetes mellitus (DM) has gained much attention. However, less firm evidence comes from data to augment our understanding of the role of F. deltoidea and vitexin in protecting pancreatic β-cells. The aim of this study was to assess histological and oxidative stress changes in the pancreas of streptozotocin (STZ)-induced diabetic rats following F. deltoidea extract and vitexin treatment.

    METHODS: F. deltoidea and vitexin was administrated orally to six-weeks STZ-induced diabetic rats over 8 weeks period. The glucose and insulin tolerances were assessed by intraperitoneal glucose (2 g/kg) tolerance test (IPGTT) and intraperitoneal insulin (0.65 U/kg) tolerance test (IPITT), respectively. Subsequently, insulin resistance was assessed by homeostasis assessment model of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI) and the insulin/triglyceride-derived McAuley index. The histological changes in the pancreas were then observed by hematoxylin-eosin (H&E) staining. Further, the pattern of fatty acid composition and infrared (IR) spectra of the serum and pancreas were monitored by gas chromatography (GC) method and Fourier Transform Infrared (FT-IR) spectroscopy.

    RESULTS: F. deltoidea and vitexin increased pancreatic antioxidant enzymes and promoted islet regeneration. However, a significant increase in insulin secretion was observed only in rats treated with F. deltoidea. More importantly, reduction of fasting blood glucose is consistent with reduced FT-IR peaks at 1200-1000 cm-1.

    CONCLUSIONS: These results accentuate that F. deltoidea and vitexin could be a potential agent to attenuate pancreatic oxidative damage and advocate their therapeutic potential for treating DM.

    Matched MeSH terms: Insulin/metabolism*
  16. Zhong L, Liu Q, Ting YS, Thien VY, Binti Kalong NS, Yang D, et al.
    Chem Biol Drug Des, 2018 12;92(6):1998-2008.
    PMID: 30043441 DOI: 10.1111/cbdd.13371
    Overexpression of thioredoxin-interacting protein (TXNIP) is associated with reduced insulin sensitivity and β-cell apoptosis. We have previously shown that W2476 inhibited high glucose-induced TXNIP expression at both mRNA and protein levels in INS-1E cells. In this study, we describe structural modification and optimization of W2476 leading to three more active derivatives, 8d, 8g, and 9h, capable of suppressing TXNIP expression in BG73 and INS-1E cells, increasing insulin production, and reducing high glucose-induced apoptosis in INS-1E cells.
    Matched MeSH terms: Insulin/metabolism
  17. Gupta G, Singhvi G, Chellappan DK, Sharma S, Mishra A, Dahiya R, et al.
    Panminerva Med, 2018 Sep;60(3):109-116.
    PMID: 30176701 DOI: 10.23736/S0031-0808.18.03462-6
    Glioblastoma, also known as glioblastoma multiforme, is the most common and worldwide-spread cancer that begins within the brain. Glioblastomas represent 15% of brain tumors. The most common length of survival following diagnosis is 12 to 14 months with less than 3% to 5% of people surviving longer than five years. Without treatment, survival is typically 3 months. Among all receptors, special attention has been focused on the role of peroxisome proliferator-activated receptors (PPARs) in glioblastoma. PPARs are ligand-activated intracellular transcription factors. The PPAR subfamily consists of three subtypes encoded by distinct genes named PPARα, PPARβ/δ, and PPARγ. PPARγ is the most extensively studied subtype of PPAR. There has been interesting preliminary evidence suggesting that diabetic patients receiving PPARγ agonists, a group of anti-diabetics, thiazolidinedione drugs, have an increased median survival for glioblastoma. In this paper, the recent progresses in understanding the potential mechanism of PPARγ in glioblastoma are summarized.
    Matched MeSH terms: Insulin/metabolism
  18. Shaik MM, Gan SH, Kamal MA
    CNS Neurol Disord Drug Targets, 2014 Mar;13(2):283-9.
    PMID: 24074446 DOI: 10.2174/18715273113126660181
    Cognitive decline is a debilitating feature of Alzheimer's disease (AD). The causes leading to such impairment are still poorly understood and effective treatments for AD are still unavailable. Type 2 diabetes mellitus (T2DM) has been identified as a risk factor for AD due to desensitisation of insulin receptors in the brain. Recent studies have suggested that epigenetic mechanisms may also play a pivotal role in the pathogenesis of both AD and T2DM. This article describes the correlation between AD and T2DM and provides the insights to the epigenetics of AD. Currently, more research is needed to clarify the exact role of epigenetic regulation in the course and development of AD and also in relation to insulin. Research conducted especially in the earlier stages of the disease could provide more insight into its underlying pathophysiology to help in early diagnosis and the development of more effective treatment strategies.
    Matched MeSH terms: Insulin/metabolism
  19. Chia LL, Jantan I, Chua KH
    Curr Pharm Biotechnol, 2017;18(7):560-568.
    PMID: 28786357 DOI: 10.2174/1389201018666170808144703
    BACKGROUND: Tocotrienols (T3) are the naturally occurring vitamin E derivatives that possess antioxidant properties and therapeutic potential in diabetic complications. The bioactivities of the derivatives are determined by the number and arrangement of methyl substitution on the structure.

    OBJECTIVE: The objective of this study was to determine the effects of T3 derivatives, σ-T3, γ-T3 and α-T3 on insulin secretion of rat pancreatic islets in a dynamic culture.

    METHOD: Pancreatic islets isolated from male Wistar rats were treated with T3 for 1 h at 37°C in a microfluidic system with continuous operation that provided a stable cell culture environment. Glucose (2.8 mM and 16.7 mM, as basal and stimulant, respectively) and potassium chloride (KCl) (30 mM) were added to the treatment in calcium free medium. The supernatant was collected for insulin measurements.

    RESULTS: Short-term exposure (1 h) of σ-T3 to β cells in the stimulant glucose condition significantly potentiated insulin secretion in a dose-dependent manner. γ-T3 and α-T3 also displayed dosedependent effect but were less effective in the activation of insulin secretion. Essentially, KCl, a pancreatic β cell membrane depolarizing agent, added into the treatment further enhanced the insulin secretion of σ-T3, γ-T3 and α-T3 with ED50 values of 504, 511 and 588 µM, respectively.

    CONCLUSION: The findings suggest the potential of σ-T3 in regulating glucose-stimulated insulin secretion (GSIS) in response to the intracellular calcium especially in the presence of KCl.

    Matched MeSH terms: Insulin/metabolism*
  20. Azman M, Sani A, Kamaruddin NA
    Ann Saudi Med, 2014;34(6):476-81.
    PMID: 25971819 DOI: 10.5144/0256-4947.2014.476
    BACKGROUND AND OBJECTIVES: Obstructive sleep apnea (OSA) is a common disease affecting middle-aged patients and is associated with significant cardiovascular, cerebrovascular, and metabolic complications. Current evidences show inconclusive association between OSA and insulin resistance (IR). This study aims to examine the possible correlation between OSA parameters and IR.

    DESIGN AND SETTINGS: This was a cross-sectional study to examine the association between OSA parameters and IR using homeostasis model assessment (HOMA) on patients who underwent polysomnogram (PSG) in a tertiary center between March 2011 and March 2012 (1 year).

    PATIENTS AND METHODS: A total of 62 patients underwent PSG within the study period, of which 16 patients were excluded due to abnormal fasting blood sugar. Information on patients' medical illnesses, medications, and Epworth sleepiness scale (ESS) was obtained. Patients' body mass index (BMI), neck circumference, and waist circumference (WC) were measured. Blood samples were collected after 8 hours of fasting to measure HOMA-IR value. Overnight PSG was performed for all patients. Data was recorded and analyzed using SPSS, version 12.0 (SPSS Inc, Chicago, USA).

    RESULTS: The prevalence of IR in OSA patients was 64.3%. There was significant correlation between OSA parameters (apnea-hypopnea index, ESS, BMI, and WC) and HOMA-IR with correlation coefficient of 0.529, 0.224, 0.261, and 0.354, respectively.

    CONCLUSION: A linear correlation exists between OSA parameters and IR concluding a definite causal link between OSA and IR. IR screening is recommended in severe OSA patients.

    Matched MeSH terms: Insulin/metabolism*
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