Potential Therapeutic Applications of Synthetic Conotoxin s-cal14.2b, Derived from <i>Californiconus californicus</i>, for Treating Type 2 Diabetes
The FDA’s approval of peptide drugs such as Ziconotide or Exendin for pain relief and diabetes treatment, respectively, enhanced the interest to explore novel conotoxins from <i>Conus</i> species venom. In general, conotoxins can be used in pathologies where voltage-gated channels, membr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/8/936 |
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| author | Pavel H. Lugo-Fabres Leslie M. Otero-Sastre Johanna Bernáldez-Sarabia Tanya A. Camacho-Villegas Noemi Sánchez-Campos Janeth Serrano-Bello Luis A. Medina Saé Muñiz-Hernández Lizbeth de la Cruz Isabel Arenas Antonio Barajas-Martínez David E. Garcia Linda Nuñez-Garcia Jorge González-Canudas Alexei F. Licea-Navarro |
| author_facet | Pavel H. Lugo-Fabres Leslie M. Otero-Sastre Johanna Bernáldez-Sarabia Tanya A. Camacho-Villegas Noemi Sánchez-Campos Janeth Serrano-Bello Luis A. Medina Saé Muñiz-Hernández Lizbeth de la Cruz Isabel Arenas Antonio Barajas-Martínez David E. Garcia Linda Nuñez-Garcia Jorge González-Canudas Alexei F. Licea-Navarro |
| author_sort | Pavel H. Lugo-Fabres |
| collection | DOAJ |
| description | The FDA’s approval of peptide drugs such as Ziconotide or Exendin for pain relief and diabetes treatment, respectively, enhanced the interest to explore novel conotoxins from <i>Conus</i> species venom. In general, conotoxins can be used in pathologies where voltage-gated channels, membrane receptors, or ligands alter normal physiological functions, as in metabolic diseases such as Type 2 diabetes. In this study, the synthetic cal14.2b (s-cal14.2b) from the unusual <i>Californiconus californicus</i> demonstrated bioactivity on NIT-1 insulinoma cell lines stimulating insulin secretion detecting by high performance liquid chromatography (HPLC). Accordingly, s-cal14.2b increased the Ca<sub>V</sub>1.2/1.3 channel-current by 35 ± 4% with a recovery τ of 10.3 ± 4 s in primary cell culture of rat pancreatic β-cells. The in vivo results indicated a similar effect of insulin secretion on mice in the glucose tolerance curve model by reducing the glucose from 500 mg/dL to 106 mg/dL in 60 min, compared to the negative control of 325 mg/dL at the same time. The PET-SCAN with radiolabeling 99mTc-s-cal14.2b demonstrated biodistribution and accumulation in rat pancreas with complete depuration in 24 h. These findings show the potential therapeutic use of s-cal14.2b in endocrinal pathologies such as early stages of Type 2 Diabetes where the pancreas’s capability to produce insulin is still effective. |
| first_indexed | 2024-03-10T08:59:02Z |
| format | Article |
| id | doaj.art-01f8ce17a0e34d9788ee9d908f890651 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T08:59:02Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-01f8ce17a0e34d9788ee9d908f8906512023-11-22T06:52:14ZengMDPI AGBiomedicines2227-90592021-08-019893610.3390/biomedicines9080936Potential Therapeutic Applications of Synthetic Conotoxin s-cal14.2b, Derived from <i>Californiconus californicus</i>, for Treating Type 2 DiabetesPavel H. Lugo-Fabres0Leslie M. Otero-Sastre1Johanna Bernáldez-Sarabia2Tanya A. Camacho-Villegas3Noemi Sánchez-Campos4Janeth Serrano-Bello5Luis A. Medina6Saé Muñiz-Hernández7Lizbeth de la Cruz8Isabel Arenas9Antonio Barajas-Martínez10David E. Garcia11Linda Nuñez-Garcia12Jorge González-Canudas13Alexei F. Licea-Navarro14CONACYT-Unidad de Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ) A. C., Av. Normalistas 800, Colinas de la Normal, Guadalajara 44270, Jalisco, MexicoDepartamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Carretera Ensenada-Tijuana No. 3918, Zona Playitas, Ensenada 22860, Baja California, MexicoDepartamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Carretera Ensenada-Tijuana No. 3918, Zona Playitas, Ensenada 22860, Baja California, MexicoCONACYT-Unidad de Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ) A. C., Av. Normalistas 800, Colinas de la Normal, Guadalajara 44270, Jalisco, MexicoDepartamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Carretera Ensenada-Tijuana No. 3918, Zona Playitas, Ensenada 22860, Baja California, MexicoLaboratorio de Bioingeniería de Tejidos, División de Estudios de Posgrado e Investigación, Facultad de Odontología, Universidad Nacional Autónoma de México, Ciudad de México 04360, MexicoLaboratorio de Física Médica-Unidad de Investigación Biomédica en Cáncer-INCan, Ciudad de México 14080, MexicoLaboratorio de Oncología Experimental, Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Ciudad de México 14080, MexicoDepartamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México 04510, MexicoDepartamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México 04510, MexicoDepartamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México 04510, MexicoDepartamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México 04510, MexicoLaboratorios Silanes S.A. de C.V., Ciudad de México 11000, MexicoLaboratorios Silanes S.A. de C.V., Ciudad de México 11000, MexicoDepartamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Carretera Ensenada-Tijuana No. 3918, Zona Playitas, Ensenada 22860, Baja California, MexicoThe FDA’s approval of peptide drugs such as Ziconotide or Exendin for pain relief and diabetes treatment, respectively, enhanced the interest to explore novel conotoxins from <i>Conus</i> species venom. In general, conotoxins can be used in pathologies where voltage-gated channels, membrane receptors, or ligands alter normal physiological functions, as in metabolic diseases such as Type 2 diabetes. In this study, the synthetic cal14.2b (s-cal14.2b) from the unusual <i>Californiconus californicus</i> demonstrated bioactivity on NIT-1 insulinoma cell lines stimulating insulin secretion detecting by high performance liquid chromatography (HPLC). Accordingly, s-cal14.2b increased the Ca<sub>V</sub>1.2/1.3 channel-current by 35 ± 4% with a recovery τ of 10.3 ± 4 s in primary cell culture of rat pancreatic β-cells. The in vivo results indicated a similar effect of insulin secretion on mice in the glucose tolerance curve model by reducing the glucose from 500 mg/dL to 106 mg/dL in 60 min, compared to the negative control of 325 mg/dL at the same time. The PET-SCAN with radiolabeling 99mTc-s-cal14.2b demonstrated biodistribution and accumulation in rat pancreas with complete depuration in 24 h. These findings show the potential therapeutic use of s-cal14.2b in endocrinal pathologies such as early stages of Type 2 Diabetes where the pancreas’s capability to produce insulin is still effective.https://www.mdpi.com/2227-9059/9/8/936<i>Californiconus californicus</i>conotoxinss-cal14.2btype 2 diabetesconodrugs |
| spellingShingle | Pavel H. Lugo-Fabres Leslie M. Otero-Sastre Johanna Bernáldez-Sarabia Tanya A. Camacho-Villegas Noemi Sánchez-Campos Janeth Serrano-Bello Luis A. Medina Saé Muñiz-Hernández Lizbeth de la Cruz Isabel Arenas Antonio Barajas-Martínez David E. Garcia Linda Nuñez-Garcia Jorge González-Canudas Alexei F. Licea-Navarro Potential Therapeutic Applications of Synthetic Conotoxin s-cal14.2b, Derived from <i>Californiconus californicus</i>, for Treating Type 2 Diabetes Biomedicines <i>Californiconus californicus</i> conotoxins s-cal14.2b type 2 diabetes conodrugs |
| title | Potential Therapeutic Applications of Synthetic Conotoxin s-cal14.2b, Derived from <i>Californiconus californicus</i>, for Treating Type 2 Diabetes |
| title_full | Potential Therapeutic Applications of Synthetic Conotoxin s-cal14.2b, Derived from <i>Californiconus californicus</i>, for Treating Type 2 Diabetes |
| title_fullStr | Potential Therapeutic Applications of Synthetic Conotoxin s-cal14.2b, Derived from <i>Californiconus californicus</i>, for Treating Type 2 Diabetes |
| title_full_unstemmed | Potential Therapeutic Applications of Synthetic Conotoxin s-cal14.2b, Derived from <i>Californiconus californicus</i>, for Treating Type 2 Diabetes |
| title_short | Potential Therapeutic Applications of Synthetic Conotoxin s-cal14.2b, Derived from <i>Californiconus californicus</i>, for Treating Type 2 Diabetes |
| title_sort | potential therapeutic applications of synthetic conotoxin s cal14 2b derived from i californiconus californicus i for treating type 2 diabetes |
| topic | <i>Californiconus californicus</i> conotoxins s-cal14.2b type 2 diabetes conodrugs |
| url | https://www.mdpi.com/2227-9059/9/8/936 |
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