Generic placeholder image

Current Protein & Peptide Science

Author(s): Qian Lin, Jingtao Liu, Hengling Chen, Wenwu Hu, Weiqiong Lei, Meijie Wang, Xianguang Lin, Yongning Zhang, Huiting Ai, Su Chen and Chenhong Li*

DOI: 10.2174/0113892037249620231010063637

DownloadDownload PDF Flyer Cite As
A Novel Peptide COX52-69 Inhibits High Glucose-induced Insulin Secretion by Modulating BK Channel Activity

Page: [419 - 426] Pages: 8

  • * (Excluding Mailing and Handling)

Abstract

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

Objectives: 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.

Graphical Abstract

[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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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)