A Novel Peptide COX52-69 Inhibits High Glucose-induced Insulin Secretion by Modulating BK Channel Activity

  • Autores: Lin Q.1, Liu J.1, Chen H.2, Hu W.3, Lei W.1, Wang M.4, Lin X.1, Zhang Y.2, Ai H.2, Chen S.1, Li C.2
  • Afiliações:
    1. Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science of State Ethnic Affairs Commission, Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis and Treatment, College of Biomedical Engineering, South-Central Minzu University
    2. Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science of State Ethnic Affairs Commission, Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis and Treatment, College of Biomedical Engineering,, South-Central Minzu University
    3. Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science of State Ethnic Affairs Commission, Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis and Treatment, College of Biomedical Engineering, South-Central Minzu University,
    4. Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science of State Ethnic Affairs Commission, Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis and Treatment, College of Biomedical Engineering,, South-Central Minzu University,
  • Edição: Volume 25, Nº 5 (2024)
  • Páginas: 419-426
  • Seção: Life Sciences
  • URL: https://clinpractice.ru/1389-2037/article/view/645634
  • DOI: https://doi.org/10.2174/0113892037249620231010063637
  • ID: 645634

Citar

Texto integral

Resumo

Background:Excessive insulin is the leading cause of metabolic syndromes besides hyperinsulinemia. Insulin-lowering therapeutic peptides have been poorly studied and warrant urgent attention.

Objective:The main purpose of this study, was to introduce a novel peptide COX52-69 that was initially isolated from the porcine small intestine and possessed the ability to inhibit insulin secretion under high-glucose conditions by modulating large conductance Ca2+-activated K+ channels (BK channels) activity.

Methods and Results:Enzyme-linked immunosorbent assay results indicate that COX52-69 supressed insulin release induced by high glucose levels in pancreatic islets and animal models. Furthermore, electrophysiological data demonstrated that COX52-69 can increase BK channel currents and hyperpolarize cell membranes. Thus, cell excitability decreased, corresponding to a reduction in insulin secretion.

Conclusion:Our study provides a novel approach to modulate high glucose-stimulated insulin secretion in patients with hyperinsulinemia.

Sobre autores

Qian Lin

Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science of State Ethnic Affairs Commission, Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis and Treatment, College of Biomedical Engineering, South-Central Minzu University

Email: info@benthamscience.net

Jingtao Liu

Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science of State Ethnic Affairs Commission, Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis and Treatment, College of Biomedical Engineering, South-Central Minzu University

Email: info@benthamscience.net

Hengling Chen

Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science of State Ethnic Affairs Commission, Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis and Treatment, College of Biomedical Engineering,, South-Central Minzu University

Email: info@benthamscience.net

Wenwu Hu

Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science of State Ethnic Affairs Commission, Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis and Treatment, College of Biomedical Engineering, South-Central Minzu University,

Email: info@benthamscience.net

Weiqiong Lei

Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science of State Ethnic Affairs Commission, Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis and Treatment, College of Biomedical Engineering, South-Central Minzu University

Email: info@benthamscience.net

Meijie Wang

Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science of State Ethnic Affairs Commission, Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis and Treatment, College of Biomedical Engineering,, South-Central Minzu University,

Email: info@benthamscience.net

Xianguang Lin

Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science of State Ethnic Affairs Commission, Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis and Treatment, College of Biomedical Engineering, South-Central Minzu University

Email: info@benthamscience.net

Yongning Zhang

Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science of State Ethnic Affairs Commission, Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis and Treatment, College of Biomedical Engineering,, South-Central Minzu University

Email: info@benthamscience.net

Huiting Ai

Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science of State Ethnic Affairs Commission, Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis and Treatment, College of Biomedical Engineering,, South-Central Minzu University

Email: info@benthamscience.net

Su Chen

Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science of State Ethnic Affairs Commission, Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis and Treatment, College of Biomedical Engineering, South-Central Minzu University

Email: info@benthamscience.net

Chenhong Li

Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science of State Ethnic Affairs Commission, Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis and Treatment, College of Biomedical Engineering,, South-Central Minzu University

Autor responsável pela correspondência
Email: info@benthamscience.net

Bibliografia

  1. Moreau, F.; Kirk, N.S.; Zhang, F.; Gelfanov, V.; List, E.O.; Chrudinová, M.; Venugopal, H.; Lawrence, M.C.; Jimenez, V.; Bosch, F.; Kopchick, J.J.; DiMarchi, R.D.; Altindis, E.; Kahn, C.R. Interaction of a viral insulin-like peptide with the IGF-1 receptor produces a natural antagonist. Nat. Commun., 2022, 13(1), 6700. doi: 10.1038/s41467-022-34391-6 PMID: 36335114
  2. Templeman, N.M.; Skovsø, S.; Page, M.M.; Lim, G.E.; Johnson, J.D. A causal role for hyperinsulinemia in obesity. J. Endocrinol., 2017, 232(3), R173-R183. doi: 10.1530/JOE-16-0449 PMID: 28052999
  3. Elena, M.; Chu, A. Pediatr. Ann., 2017, 46(11), e409. PMID: 29131920
  4. (a) Dongerkery, S.P.; Schroeder, P.R.; Shomali, M.E. Insulin and its cardiovascular effects: What is the current evidence? Curr. Diab. Rep., 2017, 17(12), 120. doi: 10.1007/s11892-017-0955-3 PMID: 29058131; (b) Poirier, P.; Giles, T.D.; Bray, G.A.; Hong, Y.; Stern, J.S.; Pi-Sunyer, F.X.; Eckel, R.H. Obesity and cardiovascular disease: Pathophysiology, evaluation, and effect of weight loss. Circulation, 2006, 113(6), 898-918. doi: 10.1161/CIRCULATIONAHA.106.171016 PMID: 16380542; (c) Hamano, K.; Akita, K.; Takeuchi, Y.; Suwa, T.; Takeda, J.; Dodo, S. Glucose-responsive Insulinoma with Insulin Hypersecretion Suppressed by Metformin. Intern. Med., 2019, 58(24), 3563-3568. doi: 10.2169/internalmedicine.3318-19 PMID: 31462593
  5. Perry, R.J.; Shulman, G.I. Mechanistic links between obesity, insulin, and cancer. Trends Cancer, 2020, 6(2), 75-78. doi: 10.1016/j.trecan.2019.12.003 PMID: 32061306
  6. Hopkins, B.D.; Goncalves, M.D.; Cantley, L.C. Insulin–PI3K signalling: An evolutionarily insulated metabolic driver of cancer. Nat. Rev. Endocrinol., 2020, 16(5), 276-283. doi: 10.1038/s41574-020-0329-9 PMID: 32127696
  7. (a) Dahiya, R.; Dahiya, S.; Kumar, P.; Kumar, R.V.; Dahiya, S.; Kumar, S.; Saharan, R.; Basu, P.; Mitra, A.; Sharma, A.; Kashaw, S.K.; Patel, J.K. Structural and biological aspects of natural bridged macrobicyclic peptides from marine resources. Arch. Pharm. (Weinheim), 2021, 354(8), 2100034. doi: 10.1002/ardp.202100034 PMID: 33913195; (b) Dahiya, R.; Dahiya, S.; Fuloria, N.K.; Mourya, R.; Dahiya, S.; Fuloria, S.; Kumar, S.; Shrivastava, J.; Saharan, R.; Chennupati, S.V.; Patel, J.K. Natural Bridged Bicyclic Peptide Macrobiomolecules from Celosia argentea and Amanita phalloides. Mini Rev. Med. Chem., 2022, 22(13), 1772-1788. doi: 10.2174/1389557522666220113122117 PMID: 35049431; (c) Muttenthaler, M.; King, G.F.; Adams, D.J.; Alewood, P.F. Trends in peptide drug discovery. Nat. Rev. Drug Discov., 2021, 20(4), 309-325. doi: 10.1038/s41573-020-00135-8 PMID: 33536635
  8. (a) Hansen, P.R.; Oddo, A. Fmoc Solid-Phase Peptide Synthesis. Methods Mol. Biol., 2015, 1348, 33-50. doi: 10.1007/978-1-4939-2999-3_5 PMID: 26424261; (b) Chan, W. C.; White, P. D. Fmoc Solid-Phase Peptide Synthesis: A Practical Approach., 2000.
  9. Chen, Z.; Agerberth, B.; Gell, K.; Andersson, M.; Mutt, V.; Ostenson, C.G.; Efendić, S.; Barros-Söderling, J.; Persson, B.; Jörnvall, H. Isolation and characterization of porcine diazepam-binding inhibitor, a polypeptide not only of cerebral occurrence but also common in intestinal tissues and with effects on regulation of insulin release. Eur. J. Biochem., 1988, 174(2), 239-244. doi: 10.1111/j.1432-1033.1988.tb14088.x PMID: 3289918
  10. (a) Xie, L.; Lu, J.; Östenson, C.G.; Xu, T.; Chen, Z.W. GIP1–39, a novel insulinotropic peptide form and aspects on its mechanism of action. Regul. Pept., 2004, 121(1-3), 107-112. doi: 10.1016/j.regpep.2004.04.013 PMID: 15256280; (b) Wang, J.; Zeng, Y.; Yan, D.; Lu, J.; Chen, Z.; Li, C. Purification and characterization of novel truncated fragments of bioactive proteins from porcine intestine with effects on insulin secretion. Sci. Res. Essays, 2012, 7(34), 3026-3031. doi: 10.5897/SRE12.033
  11. (a) Bachem, M.G.; Schneider, E.; Groß, H.; Weidenbach, H.; Schmid, R.M.; Menke, A.; Siech, M.; Beger, H.; Grünert, A.; Adler, G. Identification, culture, and characterization of pancreatic stellate cells in rats and humans. Gastroenterology, 1998, 115(2), 421-432. doi: 10.1016/S0016-5085(98)70209-4 PMID: 9679048; (b) Velasco, M.; Larqué, C.; Díaz-García, C.M.; Sanchez-Soto, C.; Hiriart, M. Rat pancreatic beta-cell culture. Methods Mol. Biol., 2018, 1727, 261-273. doi: 10.1007/978-1-4939-7571-6_20 PMID: 29222788
  12. (a) Leung, Y.M.; Ahmed, I.; Sheu, L.; Tsushima, R.G.; Diamant, N.E.; Hara, M.; Gaisano, H.Y. Electrophysiological characterization of pancreatic islet cells in the mouse insulin promoter-green fluorescent protein mouse. Endocrinology, 2005, 146(11), 4766-4775. doi: 10.1210/en.2005-0803 PMID: 16109783; (b) Houamed, K.M.; Sweet, I.R.; Satin, L.S. BK channels mediate a novel ionic mechanism that regulates glucose-dependent electrical activity and insulin secretion in mouse pancreatic β-cells. J. Physiol., 2010, 588(18), 3511-3523. doi: 10.1113/jphysiol.2009.184341 PMID: 20643769
  13. Visa, M.; Alcarraz-Vizán, G.; Montane, J.; Cadavez, L.; Castaño, C.; Villanueva-Peñacarrillo, M.L.; Servitja, J.M.; Novials, A. Islet amyloid polypeptide exerts a novel autocrine action in β-cell signaling and proliferation. FASEB J., 2015, 29(7), 2970-2979. doi: 10.1096/fj.15-270553 PMID: 25808537
  14. (a) Drews, G.; Krippeit-Drews, P.; Düfer, M. Electrophysiology of islet cells. Adv. Exp. Med. Biol., 2010, 654, 115-163. doi: 10.1007/978-90-481-3271-3_7 PMID: 20217497; (b) Göpel, S.O.; Kanno, T.; Barg, S.; Weng, X.G.; Gromada, J.; Rorsman, P. Regulation of glucagon release in mouse α-cells by K ATP channels and inactivation of TTX-sensitive Na + channels. J. Physiol., 2000, 528(3), 509-520. doi: 10.1111/j.1469-7793.2000.00509.x PMID: 11060128; (c) Remedi, M.S.; Rocheleau, J.V.; Tong, A.; Patton, B.L.; McDaniel, M.L.; Piston, D.W.; Koster, J.C.; Nichols, C.G. Hyperinsulinism in mice with heterozygous loss of KATP channels. Diabetologia, 2006, 49(10), 2368-2378. doi: 10.1007/s00125-006-0367-4 PMID: 16924481
  15. (a) Nakashima, K.; Kanda, Y.; Hirokawa, Y.; Kawasaki, F.; Matsuki, M.; Kaku, K. MIN6 is not a pure beta cell line but a mixed cell line with other pancreatic endocrine hormones. Endocr. J., 2009, 56(1), 45-53. doi: 10.1507/endocrj.K08E-172 PMID: 18845907; (b) Yamato, E.; Tashiro, F.; Miyazaki, J. Microarray analysis of novel candidate genes responsible for glucose-stimulated insulin secretion in mouse pancreatic β-cell line MIN6. PLoS One, 2013, 8(4), e61211. doi: 10.1371/journal.pone.0061211 PMID: 23560115
  16. (a) Latorre, R.; Castillo, K.; Carrasquel-Ursulaez, W.; Sepulveda, R.V.; Gonzalez-Nilo, F.; Gonzalez, C.; Alvarez, O. Molecular determinants of BK channel functional diversity and functioning. Physiol. Rev., 2017, 97(1), 39-87. doi: 10.1152/physrev.00001.2016 PMID: 27807200; (b) Shangjian, L.; Zhengrong, D.; Liqiang, W.; Lei, L.; Wenting, A.; Xiling, S.; Xinyi, C. Reduction of large-conductance Ca2+-activated K+ channel with compensatory increase of nitric oxide in insulin resistant rats. Diabetes Metab. Res. Rev., 2011, 27(5), 461-469. doi: 10.1002/dmrr.1196 PMID: 21425425; (c) Neves, C.; Milton, G.; Cesaretti, M.; Kohlmann, N.; Agostinho, T.; Zanella, M.T.; Ribeiro, A.B.; Osvaldo, K. Am. J. Hypertens., (S1), A218-A218.; (d) Chamberlain, L.H.; Shipston, M.J.; Gould, G.W. Regulatory effects of protein S-acylation on insulin secretion and insulin action. Open Biol., 2021, 11(3), 210017. doi: 10.1098/rsob.210017 PMID: 33784857
  17. (a) DeCensi, A.; Puntoni, M.; Goodwin, P.; Cazzaniga, M.; Gennari, A.; Bonanni, B.; Gandini, S. Metformin and cancer risk in diabetic patients: A systematic review and meta-analysis. Cancer Prev. Res. (Phila.), 2010, 3(11), 1451-1461. doi: 10.1158/1940-6207.CAPR-10-0157 PMID: 20947488; (b) Dev, R.; Bruera, E.; Dalal, S. Insulin resistance and body composition in cancer patients. Ann. Oncol., 2018, 29, ii18-ii26. doi: 10.1093/annonc/mdx815
  18. Kim, H.J.; Lee, S.; Chun, K.H.; Jeon, J.Y.; Han, S.J.; Kim, D.J.; Kim, Y.S.; Woo, J-T.; Nam, M-S.; Baik, S.H. Medicine (Baltimore), 2018, 97(8)

Arquivos suplementares

Arquivos suplementares
Ação
1. JATS XML
Baixar

Declaração de direitos autorais © Bentham Science Publishers, 2024