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Chinese Medicine
Published in: Chinese Medicine 1/2014

Open Access 01-12-2014 | Research

Effects of a novel curcumin derivative on insulin synthesis and secretion in streptozotocin-treated rat pancreatic islets in vitro

Authors: MohammedTalaat Abdel Aziz, Mohammed Farid El-Asmar, Ameen Mahmoud Rezq, MohammedAbdel Aziz Wassef, Hanan Fouad, Nagwa Kamal Roshdy, Hanan Hosni Ahmed, Laila Ahmed Rashed, Dina Sabry, Fatma Mohammed Taha, Amira Hassouna

Published in: Chinese Medicine | Issue 1/2014

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Abstract

Background

Hyperglycemia induces activation of the c-Jun N-terminal kinase (JNK) pathway, which suppresses insulin gene expression and reduces DNA binding of pancreatic and duodenal homeobox factor (PDX)-1. This study aims to investigate the effects of a novel curcumin derivative (NCD) on JNK signaling pathway on insulin synthesis and secretion in streptozotocin (STZ)-treated rat pancreatic islets in vitro.

Methods

Isolated rat pancreatic islets were divided into five groups: untreated control group; group treated with NCD (10 μM); group exposed to STZ (5 mM); group treated with NCD (10 μM) and then exposed to STZ (5 mM); and group exposed to STZ (5 mM) and then treated with NCD (10 μM). The pancreatic islets from all groups were used for DNA fragmentation assays and quantitative assessments of the JNK, Pdx1, glucose transporter-2 (GLUT2), heme oxygenase (HO)-1, transcription factor 7-like 2 (TCF7L2), and glucagon-like peptide (GLP)-1 gene expression levels. The intracellular calcium, zinc, and the phosphorylated and total JNK protein levels were assessed. The insulin (secreted/total) and C-peptide levels were examined in islet culture medium.

Results

NCD protected pancreatic islets against STZ-induced DNA damage, improved total insulin (P = 0.001), secreted insulin (P = 0.001), and C-peptide levels (P = 0.001), normalized mRNA expressions of insulin, Pdx1, and GLUT2 (P = 0.0001), and significantly elevated calcium and zinc levels (P = 0.0001). All effects were significant when islets were treated with NCD before STZ (P = 0.05). JNK gene overexpression and JNK protein levels induced by STZ were significantly inhibited after NCD treatment of islets ( P = 0.0001). NCD-treated islets showed significantly elevated gene expressions of HO-1, TCF7L2, and GLP-1 (P = 0.0001), and these upregulated gene expressions were more significantly elevated with NCD treatment before STZ than after STZ (P = 0.05).

Conclusions

NCD improved insulin synthesis and secretion in vitro in isolated pancreatic islets treated with STZ through inhibition of the JNK pathway, up-regulation of the gene expressions of HO-1, TCF7L2, and GLP-1 and enhancing effects on calcium and zinc levels.
Appendix
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Literature
1.
Meghana K, Sanjeev G, Ramesh B: Curcumin prevents streptozotocin-induced islet damage by scavenging free radicals: a prophylactic and protective role. Eur J Pharmacol. 2007, 577: 183-191. 10.1016/j.ejphar.2007.09.002.CrossRefPubMed
2.
Derijard B, Hibi M, Wu IH, Barrett T, Su B, Deng T, Karin M, Davis RJ: JNK1: A protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell. 1994, 76: 1025-1037. 10.1016/0092-8674(94)90380-8.CrossRefPubMed
3.
Kyriakis JM, Banerjee P, Nikolakaki E, Dai T, Rubie EA, Ahmad MF, Avruch J, Woodgett JR: The stress activated protein kinase subfamily of c-Jun kinases. Nature. 1994, 369: 156-160. 10.1038/369156a0.CrossRefPubMed
4.
Kyriakis JM, Avruch J: Protein kinase cascades activated by stress and inflammatory cytokines. Bioessays. 1996, 18: 567-577. 10.1002/bies.950180708.CrossRefPubMed
5.
6.
Watada H, Kajimoto Y, Umayahara Y, Matsuoka T, Kaneto H, Fujitani Y, Kamada T, Kawamori R, Yamasaki Y: The human glucokinase geneβcell-type promoter: an essential role of insulin promoter factor 1/PDX-1 in its activation in HIT-T15 cells. Diabetes. 1996, 45: 1478-1488. 10.2337/diab.45.11.1478.CrossRefPubMed
7.
8.
Offield MF, Jetton TL, Labosky PA, Ray M, Stein RW, Magnuson MA, Hogan BL, Wright CV: PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum. Development. 1996, 122: 983-995.PubMed
9.
Sander M, German MS: The beta cell transcription factors and development of the pancreas. J Mol Med. 1997, 75: 327-340. 10.1007/s001090050118.CrossRefPubMed
10.
Habener JF, Stoffers DA: A newly discovered role of transcription factors involved in pancreas development and the pathogenesis of diabetes mellitus. Proc Assoc Am Physicians. 1998, 110: 12-21.PubMed
11.
Waeber G, Thompson N, Nicod P, Bonny C: Transcriptional activation of the GLUT2 gene by the IPF-1/STF-1/IDX-1 homeobox factor. Mol Endocrinol. 1996, 10: 1327-1334.PubMed
12.
Kanitkar M, Galande S, Bhonde R: Curcumin prevents streptozotocin-induced islet damage by scavenging free radicals:a prophylactic and protective role. Eur J Pharmacol. 2007, 577: 183-191. 10.1016/j.ejphar.2007.09.002.CrossRef
13.
Kanitkar M, Gokhale K, Galande S, Bhonde R: Novel role of curcumin in the prevention of cytokine-induced islet death in vitro and diabetogenesis in vivo. Br J Pharmacol. 2008, 155: 702-713.PubMedCentralCrossRefPubMed
14.
Chen YR, Tan TH: Inhibition of the c-Jun N-terminal kinase [JNK] signaling pathway by curcumin. Oncogene. 1998, 17 (2): 173-178. 10.1038/sj.onc.1201941.CrossRefPubMed
15.
Daval M, Bedrood S, Gurlo T, Huang CJ, Costes S, Butler PC, Langen R: The effect of curcumin on human islet amyloid polypeptide misfolding and toxicity. Amyloid. 2010, 17 (3–4): 118-128.PubMedCentralCrossRefPubMed
16.
Rezende LF, Vieira AS, Negro A, Langone F, Boschero AC: Ciliary neurotrophic factor (CNTF) signals through STAT3-SOCS3 pathway and protects rat pancreatic islets from cytokine-induced apoptosis. Cytokine. 2009, 46 (1): 65-71. 10.1016/j.cyto.2008.12.014.CrossRefPubMed
17.
Balamurugan AN, Akhov L, Selvaraj G, Pugazhenthi S: Induction of antioxidant enzymes by curcumin and its analogues in human islets: implications in transplantation. Pancreas. 2009, 38 (4): 454-460. 10.1097/MPA.0b013e318196c3e7.CrossRefPubMed
18.
Abdel Aziz MT, El-Asmar MF, El Nadi EG, Wassef MA, Ahmed HH, Rashed LA, Obaia EM, Sabry D, Hassouna AA, Abdel Aziz AT: The effect of curcumin on insulin release in rat-isolated pancreatic islets. Angiology. 2010, 61 (6): 557-566. 10.1177/0003319709356424.CrossRefPubMed
19.
Abdel Aziz MT, El-Asmar MF, El-Ibrashy IN, Rezq AM, Al-Malki AL, Wassef MA, Fouad HH, Ahmed HH, Taha FM, Hassouna AA, Morsi HM: Effect of novel water soluble curcumin derivative on experimental type- 1 diabetes mellitus (short term study). Diabetol Metab Syndr. 2012, 4 (1): 30-10.1186/1758-5996-4-30. [Epub ahead of print]PubMedCentralCrossRefPubMed
20.
Cai K, Qi D, Hou X, Wang O, Chen J, Deng B, Qian L, Liu X, Le Y: MCP-1 upregulates amylin expression in murine pancreatic β cells through ERK/JNK-AP1 and NF-κB related signaling pathways independent of CCR2. PLoS One. 2011, 6 (5): e19559-10.1371/journal.pone.0019559.PubMedCentralCrossRefPubMed
21.
Khalooghi K, Hashemi S, Mehraban N, Amiri P, Bazzaz JT, Larijani B, Amoli MM: In vitro modulation of TCF7L2 gene expression in human pancreatic cells. Mol Biol Rep. 2009, 36 (8): 2329-2332. 10.1007/s11033-009-9452-3.CrossRefPubMed
22.
Abdel Aziz MT, Motawi T, Rezq A, Mostafa T, Fouad HH, Ahmed HH, Rashed L, Sabry D, Senbel A, Al-Malki A, El-Shafiey R: Effects of a water-soluble curcumin protein conjugate vs. Pure curcumin in a diabetic model of erectile dysfunction. J Sex Med. 2012, 9 (7): 1815-1833. 10.1111/j.1743-6109.2012.02741.x.CrossRefPubMed
23.
24.
Shewade YM, Umrani M, Bhonde R: Large-scale isolation of islets by tissue culture of adult mouse pancreas. Transplant Proc. 1999, 31: 1721-1723. 10.1016/S0041-1345(99)00077-9.CrossRefPubMed
25.
Keong Tan K, Hwi Kim K: Alternanthera sessilis red ethyl acetate fraction exhibits antidiabetic potential on obese type 2 diabetic rats. Evid Base Com Altern Med. 2013, 2013: 845172-
26.
Smith CA, Williams GT, Kingston R, Jenkinson EJ, Owen JJT: Antibodies to CD3/T-cell receptor complex induce death by apoptosis in immature T cells in thymic cultures. Nature. 1989, 337: 181-184. 10.1038/337181a0.CrossRefPubMed
27.
Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB: Bioavailability of curcumin: Problems and promises. Mol Pharm. 2007, 4: 807-418. 10.1021/mp700113r.CrossRefPubMed
28.
Johansson EB, Tjalve H: Studies on the tissue-deposition and fate of [14C]-streptozotocin with special reference to the pancreatic islets. Acta Endocrinol. 1969, 89: 339-347.
29.
Okamoto H: Molecular basis of experimental diabetes: degeneration, oncogenesis and regeneration of pancreatic b-cells of islet of Langerhans. Bioassays. 1985, 2: 15-21. 10.1002/bies.950020106.CrossRef
30.
Chanpoo M, Petchpiboonthai H, Panyarachun B, Anupunpisit V: Effect of curcumin in the amelioration of pancreatic islets in streptozotocin induced diabetic mice. J Med Assoc Thai. 2010, 93: S152-S159.PubMed
31.
Kanitkar M, Bhonde R: Curcumin treatment enhances islet recovery by induction of heat shock response proteins, Hsp70 and heme-oxygenase-1, during cryopreservation. Life Sci. 2008, 82: 182-189. 10.1016/j.lfs.2007.10.026.CrossRefPubMed
32.
Weiss L, Whitmarsh AJ, Yang DD, Rincon M, Davis RJ, Flavell RA: Regulation of c-Jun NH(2)-terminal kinase (Jnk) gene expression during T cell activation. J Exp Med. 2000, 191: 139-146. 10.1084/jem.191.1.139.PubMedCentralCrossRefPubMed
33.
Finkel T, Holbrook NJ: Oxidants, oxidative stress and the biology of ageing. Nature. 2000, 408: 239-247. 10.1038/35041687.CrossRefPubMed
34.
Liu W, Schoenkerman A, Lowe WLJR: Activation of members of the mitogen-activated protein kinase family by glucose in endothelial cells. Am J Physiol Endocrinol Metab. 2000, 279 (4): E782-E790.PubMed
35.
Purves T, Middlemas A, Agthong S, Jude EB, Boulton AJ, Fernyhough P, Tomlinson DR: A role for mitogen-activated protein kinases in the etiology of diabetic neuropathy. FASEB J. 2001, 15: 2508-2514. 10.1096/fj.01-0253hyp.CrossRefPubMed
36.
Kaneto H, Xu G, Fujii N, Kim S, Weir S, Weir G: Involvement of c-Jun N-terminal Kinase in Oxidative Stress-mediated Suppression of Insulin Gene Expression. J Biol Chem. 2002, 277 (33): 30010-30018. 10.1074/jbc.M202066200.CrossRefPubMed
37.
Kaneto H, Nakatani Y, Kawamori D, Miyatsuka T, Matsuoka T: Involvement of Oxidative Stress and the JNK Pathway in Glucose Toxicity. Rev Diabet Stud. 2004, 1 (4): 165-174. 10.1900/RDS.2004.1.165.PubMedCentralCrossRefPubMed
38.
Kawamori D, Kajimoto Y, Kaneto H, Umayahara Y, Fujitani Y, Miyatsuka T, Watada H, Leibiger IB, Yamasaki Y, Hori M: Oxidative stress induces nucleo-cytoplasmic translocation of pancreatic transcription factor PDX-1 through activation of c-Jun NH2-terminal kinase. Diabetes. 2003, 52: 2896-2904. 10.2337/diabetes.52.12.2896.CrossRefPubMed
39.
Marshak S, Benshushan E, Shoshkes M, Havin L, Cerasi E, Melloul D: Functional conservation of regulatory elements in the pdx-1 gene: PDX-1 and hepatocyte nuclear factor 3beta transcription factors mediate betacell- specific expression. Mol Cell Biol. 2000, 20: 7583-7590. 10.1128/MCB.20.20.7583-7590.2000.PubMedCentralCrossRefPubMed
40.
Peshavaria M, Henderson E, Sharma A, Wright CV, Stein R: Functional characterization of the transactivation properties of the PDX-1 homeodomain protein. Mol Cell Biol. 1997, 17: 3987-3996.PubMedCentralPubMed
41.
Shu L, Sauter NS, Schulthess FT, Matveyenko AV, Oberholzer J, Maedler K: Transcription factor 7-like 2 regulates beta-cell survival and function in human pancreatic islets. Diabetes. 2008, 57: 645-653. 10.2337/db07-0847.CrossRefPubMed
42.
Yi F, Brubaker PL, Jin T: TCF-4 mediates cell type-specific regulation of proglucagon gene expression by beta-catenin and glycogen synthase kinase-3beta. J Biol Chem. 2005, 280: 1457-1464.CrossRefPubMed
43.
Saxena R, Gianniny L, Burtt NP, Lyssenko V, Giuducci C, Sjögren M, Florez JC, Almgren P, Isomaa B, Orho-Melander M, Lindblad U, Daly MJ, Tuomi T, Hirschhorn JN, Ardlie KG, Groop LC, Altshuler D: Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in nondiabetic individuals. Diabetes. 2006, 55: 2890-2895. 10.2337/db06-0381.CrossRefPubMed
44.
Damcott CM, Pollin TI, Reinhart LJ, Ott SH, Shen H, Silver KD, Mitchell BD, Shuldiner AR: Polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in the Amish: replication and evidence for a role in both insulin secretion and insulin resistance. Diabetes. 2006, 55: 2654-2659. 10.2337/db06-0338.CrossRefPubMed
45.
da Silva XG, Loder MK, McDonald A, Tarasov AI, Carzaniga R, Kronenberger K, Barg S, Rutter GA: TCF7L2 regulates late events in insulin secretion from pancreatic islet beta-cells. Diabetes. 2009, 58 (4): 894-905. 10.2337/db08-1187.CrossRef
46.
Lang J: Molecular mechanisms and regulation of insulin exocytosis as a paradigm of endocrine secretion. Eur J Biochem. 1999, 259: 3-17. 10.1046/j.1432-1327.1999.00043.x.CrossRefPubMed
47.
Malhotra A, Nair P, Dhawan DK: Curcumin and resveratrol synergistically stimulate p21 and regulate cox-2 by maintaining adequate zinc levels during lung carcinogenesis. Eur J Cancer Prev. 2011, 20 (5): 411-416. 10.1097/CEJ.0b013e3283481d71.CrossRefPubMed
48.
Kalpana C, Menon VP: Protective effect of curcumin on circulatory lipid peroxidation and antioxidant status during nicotine-induced toxicity. Toxicol Mech Methods. 2004, 14 (6): 339-343. 10.1080/15376520490434692.CrossRefPubMed
49.
Li YV: Zinc and insulin in pancreatic beta-cells. Endocrine. 2013, Aug 24. [Epub ahead of print]
50.
Istyastono EP: Docking studies of curcumin as a potential lead compound to develop novel dipeptydyl peptidase-4 inhibitors. Indo J Chem. 2009, 9 (1): 132-136.
51.
Ahrén B: Dipeptidyl peptidase-4 inhibitors: clinical data and clinical implications. Diabetes Care. 2007, 30 (6): 1344-1350. 10.2337/dc07-0233.CrossRefPubMed
52.
Chuengsamarn S, Rattanamongkolgul S, Luechapudiporn R, Phisalaphong C, Jirawatnotai S: Curcumin extract for prevention of type 2 diabetes. Diabetes Care. 2012, 35 (11): 2121-2127. 10.2337/dc12-0116.PubMedCentralCrossRefPubMed
53.
Best L, Elliott AC, Brown PD: Curcumin induces electrical activity in rat pancreatic beta-cells by activating the volume-regulated anion channel. Biochem Pharmacol. 2007, 73: 1768-1775. 10.1016/j.bcp.2007.02.006.CrossRefPubMed
54.
Aggarwal BB, Harikumar KB: Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol. 2009, 41 (1): 40-59. 10.1016/j.biocel.2008.06.010.PubMedCentralCrossRefPubMed
55.
Chang CL, Lin Y, Bartolome AP, Chen YC, Chiu SC, Yang WC: Herbal therapies for type 2 diabetes mellitus: chemistry, biology, and potential application of selected plants and compounds. Evid Based Complement Alternat Med. 2013, 2013: 378657-Epub 2013 Apr 4PubMedCentralPubMed
Metadata
Title
Effects of a novel curcumin derivative on insulin synthesis and secretion in streptozotocin-treated rat pancreatic islets in vitro
Authors
MohammedTalaat Abdel Aziz
Mohammed Farid El-Asmar
Ameen Mahmoud Rezq
MohammedAbdel Aziz Wassef
Hanan Fouad
Nagwa Kamal Roshdy
Hanan Hosni Ahmed
Laila Ahmed Rashed
Dina Sabry
Fatma Mohammed Taha
Amira Hassouna
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Chinese Medicine / Issue 1/2014
Electronic ISSN: 1749-8546
DOI
https://doi.org/10.1186/1749-8546-9-3

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