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2 "Glucose-stimulated insulin secretion"
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Hexane Extract of Orthosiphon stamineus Induces Insulin Expression and Prevents Glucotoxicity in INS-1 Cells
Hae-Jung Lee, Yoon-Jung Choi, So-Young Park, Jong-Yeon Kim, Kyu-Chang Won, Jong-Keun Son, Yong-Woon Kim
Diabetes Metab J. 2015;39(1):51-58.   Published online February 16, 2015
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  • 62 Download
  • 10 Web of Science
  • 8 Crossref
AbstractAbstract PDFPubReader   

Hyperglycemia, a characteristic feature of diabetes, induces glucotoxicity in pancreatic β-cells, resulting in further impairment of insulin secretion and worsening glycemic control. Thus, preservation of insulin secretory capacity is essential for the management of type 2 diabetes. In this study, we evaluated the ability of an Orthosiphon stamineus (OS) extract to prevent glucotoxicity in insulin-producing cells.


We measured insulin mRNA expression and glucose-stimulated insulin secretion (GSIS) in OS-treated INS-1 cells after exposure to a high glucose (HG; 30 mM) concentration.


The hexane extract of OS elevated mRNA expression of insulin as well as pancreatic and duodenal homeobox-1 of INS-1 cells in a dose-dependent manner. The hexane OS extract also increased the levels of phosphorylated phosphatidylinositol 3-kinase (PI3K) in a concentration-dependent manner. Additionally, Akt phosphorylation was elevated by treatment with 100 and 200 µmol of the hexane OS extract. Three days of HG exposure suppressed insulin mRNA expression and GSIS; these expressions were restored by treatment with the hexane OS extract. HG elevated peroxide levels in the INS-1 cells. These levels were unaffected by OS treatment under both normal and hyperglycemic conditions.


Our results suggested that the hexane extract of OS elevates insulin mRNA expression and prevents glucotoxicity induced by a 3-day treatment with HG. This was associated with the activation of PI-3K and Akt.


Citations to this article as recorded by  
  • An Updated Review of Ethnobotany, Ethnopharmacology, Phytochemistry and Pharmacological Activities of Orthosiphon stamineus Benth
    Anandarajagopal Kalusalingam, Dania Najiha Hasnu, Abdullah Khan, Ching Siang Tan, Bama Menon, Venkateshan Narayanan, Khang Wen Goh, Asmuni Mohd Ikmal, Noraini Talip, Poonguzhali Subramanian, Long Chiau Ming
    Malaysian Applied Biology.2024; 53(1): 1.     CrossRef
  • Scopoletin protects INS-1 pancreatic β cells from glucotoxicity by reducing oxidative stress and apoptosis
    Jae Eun Park, Ji Sook Han
    Toxicology in Vitro.2023; 93: 105665.     CrossRef
  • A Systematic Review of Orthosiphon stamineus Benth. in the Treatment of Diabetes and Its Complications
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    Molecules.2022; 27(2): 444.     CrossRef
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    International Journal of Molecular Sciences.2019; 20(10): 2458.     CrossRef
  • Understanding glycaemic control and current approaches for screening antidiabetic natural products from evidence-based medicinal plants
    Chintha Lankatillake, Tien Huynh, Daniel A. Dias
    Plant Methods.2019;[Epub]     CrossRef
  • 50% Ethanol extract of Orthosiphon stamineus modulates genotoxicity and clastogenicity induced by mitomycin C
    Dhamraa Waleed Al-dualimi, Aman Shah Abdul Majid, Sarah Furqan Faisal Al-Shimary, Amal Aziz Al-Saadi, Raghdaa Al Zarzour, Muhammad Asif, Chern Ein Oon, Amin Malik Shah Abdul Majid
    Drug and Chemical Toxicology.2018; 41(1): 82.     CrossRef
  • Can Tea Extracts Exert a Protective Effect Against Diabetes by Reducing Oxidative Stress and Decreasing Glucotoxicity in Pancreatic β-Cells?
    Heeyoung Chae, Patrick Gilon
    Diabetes & Metabolism Journal.2015; 39(1): 27.     CrossRef
Fuel-Stimulated Insulin Secretion Depends upon Mitochondria Activation and the Integration of Mitochondrial and Cytosolic Substrate Cycles
Gary W. Cline
Diabetes Metab J. 2011;35(5):458-465.   Published online October 31, 2011
  • 65,535 View
  • 38 Download
  • 9 Crossref
AbstractAbstract PDFPubReader   

The pancreatic islet β-cell is uniquely specialized to couple its metabolism and rates of insulin secretion with the levels of circulating nutrient fuels, with the mitochondrial playing a central regulatory role in this process. In the β-cell, mitochondrial activation generates an integrated signal reflecting rates of oxidativephosphorylation, Kreb's cycle flux, and anaplerosis that ultimately determines the rate of insulin exocytosis. Mitochondrial activation can be regulated by proton leak and mediated by UCP2, and by alkalinization to utilize the pH gradient to drive substrate and ion transport. Converging lines of evidence support the hypothesis that substrate cycles driven by rates of Kreb's cycle flux and by anaplerosis play an integral role in coupling responsive changes in mitochondrial metabolism with insulin secretion. The components and mechanisms that account for the integrated signal of ATP production, substrate cycling, the regulation of cellular redox state, and the production of other secondary signaling intermediates are operative in both rodent and human islet β-cells.


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Diabetes Metab J : Diabetes & Metabolism Journal