Regulation of Intestinal GLP-1 and GLUT2 genes underlie hypoglycemia in Desplatsia subericarpa (Bocq)-Fed Wistar Rats

Subject Areas : Journal of Medicinal Herbs, "J. Med Herb" (Formerly known as Journal of Herbal Drugs or J. Herb Drug)

الاپسی اموتیووای ¹ , اوواکپری-یوو اقال ² , ایدو مکدونالد ³

1 - Center for Bio-Computing and Drug Development, Adekunle Ajasin University, Akungba-Akoko
2 - Department of Plant Biology and Biotechnology, University of Benin, Benin City, P.M.B. 1154. Edo State, Nigeria
3 - Department of Plant Biology and Biotechnology, University of Benin, Benin City, P.M.B. 1154. Edo State, Nigeria

Received: 2017-08-19 Accepted : 2017-08-19 Published : 2017-07-23

Keywords: Diabetes, Glucagon-like peptide-1, Glucose transporter 2, Kidney injury molecule-1, Iinterleukin-1-, Desplatsia subericarpa,

Abstract :

Background & Aim:Indigenous people of West Africa use the whole-leaf of Desplatsia subericarpa (Bocq) in anti-diabetic soup delicacy. This study was designed to validate the anti-diabetic claims and delineating possible mechanisms. Experimental:RT-PCR method was used to investigate regulation of intestinal glucose transporter 2 (GLUT2) and glucagon-like peptide-1 (GLP-1), and pancreatic insulin, L-type voltage-gated calcium channel genes. Insulin exocytosis was also monitored using ELISA method. The kidney sample was investigated for biomarkers of injury (kidney injury molecule-1 (KIM-1) and interleukin-1-β (IL-1β)). Results: GLP-1 up-regulation, GLUT2 down-regulation and increased insulin exocytosis but not increased insulin gene expression was observed in animals after a 3-day culinary exposure to D. Subericarpa leaves. This mechanism may explain hypoglycemia in streptozotocin-induced diabetes in animals in this study. KIM-1 and IL-1-β genes were marked up regulated in normal animals exposed (14-day) to D. Subericarpa. Recommended applications/industries: D. Subericarpa whole leaf contains phytochemicals principles with anti-diabetic potency but may be nephrotoxic. Therefore, for clinical use, selective fractionation of active components from the toxic components is desirable.

References:

Andreucci, M., Faga, T., Riccio, E., Sabbatini, M., Pisani, A., & Michael, A. 2016. The potential use of biomarkers in predicting contrast-induced acute kidney injury. Int J Nephrol Renovasc Dis, 9, 205-221.

Barham, D., & Trinder, P. 1972. An improved colour reagent for the determination of blood glucose by the oxidase system. Analyst, 97(151), 142-145.

Brown, M. S., & Goldstein, J. L. 1999. A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood. Proc Natl Acad Sci U S A, 96(20), 11041-11048.

Burkill, H. M. 2000. The useful plants of West Africa. (2 ed. Vol. 5). United Kingdom: families S-Z, Addenda. Royal Botanic Gardens, Kew, Richmond,.

Chen, L., Alam, T., Johnson, J. H., Hughes, S., Newgard, C. B., & Unger, R. H. (1990. Regulation of beta-cell glucose transporter gene expression. Proc Natl Acad Sci U S A, 87(11), 4088-4092.

Ezcurra, M., Reimann, F., Gribble, F. M., & Emery, E. 2013. Molecular mechanisms of incretin hormone secretion. Curr Opin Pharmacol, 13(6), 922-927.

Faubel, S., Lewis, E. C., Reznikov, L., Ljubanovic, D., Hoke, T. S., Somerset, H., . . . Edelstein, C. L. 2007. Cisplatin-induced acute renal failure is associated with an increase in the cytokines interleukin (IL)-1beta, IL-18, IL-6, and neutrophil infiltration in the kidney. J Pharmacol Exp Ther, 322(1), 8-15.

Im, S. S., Kang, S. Y., Kim, S. Y., Kim, H. I., Kim, J. W., Kim, K. S., & Ahn, Y. H. 2005. Glucose-stimulated upregulation of GLUT2 gene is mediated by sterol response element-binding protein-1c in the hepatocytes. Diabetes, 54(6), 1684-1691.

Inoue, N., Shimano, H., Nakakuki, M., Matsuzaka, T., Nakagawa, Y., Yamamoto, T., . . . Yamada, N. 2005. Lipid synthetic transcription factor SREBP-1a activates p21WAF1/CIP1, a universal cyclin-dependent kinase inhibitor. Mol Cell Biol, 25(20), 8938-8947.

Jafri, L., Saleem, S., Calderwood, D., Gillespie, A., Mirza, B., & Green, B. D. 2016. Naturally-occurring TGR5 agonists modulating glucagon-like peptide-1 biosynthesis and secretion. Peptides, 78, 51-58.

Keay, R. W. J. 1958. Flora of West Africa (2 ed. Vol. 1, part 2). London, United Kingdom: Crown Agents for OverseaGovernment and Administrations.

Kellett, G. L., & Helliwell, P. A. 2000. The diffusive component of intestinal glucose absorption is mediated by the glucose-induced recruitment of GLUT2 to the brush-border membrane. Biochem J, 350 Pt 1, 155-162.

Lan, H., Lin, H. V., Wang, C. F., Wright, M. J., Xu, S., Kang, L., . . . Kowalski, T. J. 2012. Agonists at GPR119 mediate secretion of GLP-1 from mouse enteroendocrine cells through glucose-independent pathways. Br J Pharmacol, 165(8), 2799-2807.

Lee, C. T., Wu, M. S., Lu, K., & Hsu, K. T. 1999. Renal tubular acidosis, hypokalemic paralysis, rhabdomyolysis, and acute renal failure--a rare presentation of Chinese herbal nephropathy. Ren Fail, 21(2), 227-230.

Leto, D., & Saltiel, A. R. 2012. Regulation of glucose transport by insulin: traffic control of GLUT4. Nat Rev Mol Cell Biol, 13(6), 383-396.

MacDonald, P. E., El-Kholy, W., Riedel, M. J., Salapatek, A. M., Light, P. E., & Wheeler, M. B. 2002. The multiple actions of GLP-1 on the process of glucose-stimulated insulin secretion. Diabetes, 51 Suppl 3, S434-442.

Marchetti, P., Lupi, R., Del Guerra, S., Bugliani, M., D'Aleo, V., Occhipinti, M., . . . Masini, M. 2009. Goals of treatment for type 2 diabetes: beta-cell preservation for glycemic control. Diabetes Care, 32 Suppl 2, S178-183.

McKillop, A. M., Moran, B. M., Abdel-Wahab, Y. H., Gormley, N. M., & Flatt, P. R. 2016. Metabolic effects of orally administered small-molecule agonists of GPR55 and GPR119 in multiple low-dose streptozotocin-induced diabetic and incretin-receptor-knockout mice. Diabetologia. 59(12):2674-85.

Meloni, A. R., DeYoung, M. B., Lowe, C., & Parkes, D. G. 2013. GLP-1 receptor activated insulin secretion from pancreatic beta-cells: mechanism and glucose dependence. Diabetes Obes Metab, 15(1), 15-27.

Nistor Baldea, L. A., Martineau, L. C., Benhaddou-Andaloussi, A., Arnason, J. T., Levy, E., & Haddad, P. S. 2010. Inhibition of intestinal glucose absorption by anti-diabetic medicinal plants derived from the James Bay Cree traditional pharmacopeia. J Ethnopharmacol, 132(2), 473-482.

Nohturfft, A., DeBose-Boyd, R. A., Scheek, S., Goldstein, J. L., & Brown, M. S. 1999. Sterols regulate cycling of SREBP cleavage-activating protein (SCAP) between endoplasmic reticulum and Golgi. Proc Natl Acad Sci U S A, 96(20), 11235-11240.

Pols, T. W., Auwerx, J., & Schoonjans, K. 2010. Targeting the TGR5-GLP-1 pathway to combat type 2 diabetes and non-alcoholic fatty liver disease. Gastroenterol Clin Biol, 34(4-5), 270-273.

Sato, H., Genet, C., Strehle, A., Thomas, C., Lobstein, A., Wagner, A., . . . Saladin, R. 2007. Anti-hyperglycemic activity of a TGR5 agonist isolated from Olea europaea. Biochem Biophys Res Commun, 362(4), 793-798.

Schaap, F. G., Trauner, M., & Jansen, P. L. 2014. Bile acid receptors as targets for drug development. Nat Rev Gastroenterol Hepatol, 11(1), 55-67.

Velasquez, D. A., Beiroa, D., Vazquez, M. J., Romero, A., Lopez, M., Dieguez, C., & Nogueiras, R. 2010. Central GLP-1 actions on energy metabolism. Vitam Horm, 84, 303-317.

Wacker, D. A., Wang, Y., Broekema, M., Rossi, K., O'Connor, S., Hong, Z., . . . Robl, J. A. 2014. Discovery of 5-chloro-4-((1-(5-chloropyrimidin-2-yl)piperidin-4-yl)oxy)-1-(2-fluoro-4-(methyls ulfonyl)phenyl)pyridin-2(1H)-one (BMS-903452), an antidiabetic clinical candidate targeting GPR119. J Med Chem, 57(18), 7499-7508.