Archives

  • 2018-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • Introduction Nicotinic acid niacin NA has

    2021-09-10

    Introduction Nicotinic Anti-cancer Compound Library sale (niacin, NA) has been used in the treatment of dislipidemia and cardiovascular disease for almost 60years (Offermanns, 2006). Large clinical studies showed that niacin alone or in combination with LDL-lowering drugs improved cardiovascular outcomes (Canner et al., 1986, Taylor et al., 2004). Recent studies demonstrate that activation of niacin receptor GPR109A, whose cognate ligand has been identified as one of the ketone bodies β-hydroxybutyrate (BHB) (Taggart et al., 2005), causes Gi-mediated inhibition of adenylyl cyclase in adipocytes, leading to reduced production of free fatty acids (FFAs) (Wise et al., 2003a, Tunaru et al., 2003 and Wise et al., 2003b). In addition to its anti-lipolytic effects, niacin also exerts beneficial anti-inflammatory actions through the activation of the GPR109A receptor. It is reported that niacin can suppress pro-atherogenic chemokines and upregulate the atheroprotective adiponectin in adipocytes (Digby et al., 2010), and also significantly inhibit TNF-α, IL-6, IL-12p40, and IL-1β production in bone marrow-derived macrophages (Zandi-Nejad et al., 2013). Moreover, GPR109A activation by dietary or pharmacological means instructs a subset of monocytes and/or macrophages to deliver a neuroprotective signal to the brain (Rahman et al., 2014). Further, niacin is able to improve endothelial function and attenuate vascular inflammation and oxidative stress (Si et al., 2014). GPR109A also plays an anti-inflammatory role in the retinal pigment epithelium and may have biological importance in diabetic retinopathy (Gambhir et al., 2012). GPR109A is expressed in colonic and intestinal epithelial cells, whose signaling promotes protective activity against inflammation and colorectal cancer (Singh et al., 2014). GPR109A activation by niacin has been speculated to provide a novel treatment approach for Parkinson’s disease (PD) partially by reducing inflammation in the brain (Wakade et al., 2014a, Wakade et al., 2014b). Actually, significant up-regulation of GPR109A levels in the blood as well as in the substantia nigra (SN) and rostral ventrolateral medulla has been observed in PD individuals and animal model (Wakade et al., 2014a, Wakade et al., 2014b, Rezq and Abdel-Rahman, 2015). Lastly, GPR109A has been detected in hypothalamic cells, whose activation leads to inhibition of synthesis and secretion of the growth hormone-releasing hormone (Fu et al., 2015). The major side effect of niacin, skin flushing, is mediated by GPR109A in keratinocytes as well as Langerhans cells in the skin (Hanson et al., 2010, Maciejewski-Lenoir et al., 2006), leading to the release of various vasodilative prostanoids. Skin flushing is not harmful but has greatly reduced the niacin compliance. However, chronic niacin medication has been associated with deterioration of glycemic control in diabetic patients, including decreased insulin sensitivity and elevated glycosylated hemoglobin levels (Garg and Grundy, 1990, Chang et al., 2006, Goldberg and Jacobson, 2008). We had offered a possible explanation with the finding of GPR109A in islet beta-cells, and that stimulation with niacin led to reduced GSIS (Li et al., 2011). Consistent with our observation, Chen et al demonstrated that decrease of GSIS from INS-1E islet beta-cells in the presence of niacin is partially modulated through activation of GPR109A-induced ROS-PPARγ-UCP2 pathways (Chen et al., 2015). We observed previously that mRNA levels of GPR109A, NF-κB, and IL-1β were higher in peripheral blood leukocytes of type 2 diabetes (T2DM), while high glucose inhibited GPR109A mRNA expression in MIN6 islet β-cells (Yang et al., 2015). Here, in the present study, we aimed to examine Anti-cancer Compound Library sale the expression of GPR109A in human islet β-cells. The results showed that GPR109A was down-regulated significantly in T2DM, implying an important role of GPR109A in the prevention of diabetes.
    Materials and methods
    Results
    Discussion In this study, we verified the expression of niacin receptor, GPR109A, in human islet beta-cells using two commercially available polyclonal antibodies (Santa Cruz and Abcam, A/B). For unknown reason, most of the alpha-cells were stained positive with the antibody from Santa Cruz, but negative with the Abcam antibody, suggesting the latter probably has a higher specificity. Lastly, the in situ hybridization staining with specific oligo-probes firmly demonstrated the expression of GPR109A but not GPR109B in human islet beta-cells (Fig. 3).