Potential Therapeutic Applications of Synthetic Conotoxin s-cal14.2b, Derived from Californiconus californicus, for Treating Type 2 Diabetes
| Autor: | Leslie M Otero-Sastre, Johanna Bernáldez-Sarabia, Noemi Sánchez-Campos, Janeth Serrano-Bello, Pavel H. Lugo-Fabres, Saé Muñiz-Hernández, Linda Nuñez-Garcia, David E. García, Alexei F. Licea-Navarro, Tanya A. Camacho-Villegas, Antonio Barajas-Martínez, Isabel Arenas, Luis A. Medina, Lizbeth de la Cruz, Jorge Gonzalez-Canudas |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Biodistribution Californiconus californicus QH301-705.5 medicine.medical_treatment conodrugs Medicine (miscellaneous) 030209 endocrinology & metabolism Type 2 diabetes Pharmacology General Biochemistry Genetics and Molecular Biology conotoxins 03 medical and health sciences 0302 clinical medicine In vivo medicine s-cal14.2b Conotoxin Biology (General) Insulinoma Ziconotide Chemistry Insulin medicine.disease 030104 developmental biology medicine.anatomical_structure type 2 diabetes Pancreas medicine.drug |
| Zdroj: | Biomedicines Volume 9 Issue 8 Biomedicines, Vol 9, Iss 936, p 936 (2021) |
| ISSN: | 2227-9059 |
| DOI: | 10.3390/biomedicines9080936 |
| Popis: | 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 Conus 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 Californiconus californicus demonstrated bioactivity on NIT-1 insulinoma cell lines stimulating insulin secretion detecting by high performance liquid chromatography (HPLC). Accordingly, s-cal14.2b increased the CaV1.2/1.3 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. |
| Databáze: | OpenAIRE |
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