Temporin A (FLPLIGRVLSGIL-NH2 ), temporin F (FLPLIGKVLSGIL-NH2 ), and temporin G (FFPVIGRILNGIL-NH2 ), first identified in skin secretions of the frog Rana temporaria, produced concentration-dependent stimulation of insulin release from BRIN-BD11 rat clonal β-cells at concentrations ≥1 nM, without cytotoxicity at concentrations up to 3 μM. Temporin A was the most effective. The mechanism of insulinotropic action did not involve an increase in intracellular Ca2+ concentrations. Temporins B, C, E, H, and K were either inactive or only weakly active. Temporins A, F, and G also produced a concentration-dependent stimulation of insulin release from 1.1B4 human-derived pancreatic β-cells, with temporin G being the most potent and effective, and from isolated mouse islets. The data indicate that cationicity, hydrophobicity, and the angle subtended by the charged residues in the temporin molecule are important determinants for in vitro insulinotropic activity. Temporin A and F (1 μM), but not temporin G, protected BRIN-BD11 cells against cytokine-induced apoptosis (P < 0.001) and augmented (P < 0.001) proliferation of the cells to a similar extent as glucagon-like peptide-1. Intraperitoneal injection of temporin G (75 nmol/kg body weight) together with a glucose load (18 mmol/kg body weight) in C57BL6 mice improved glucose tolerance with a concomitant increase in insulin secretion whereas temporin A and F administration was without significant effect on plasma glucose levels. The study suggests that combination therapy involving agents developed from the temporin A and G sequences may find application in Type 2 diabetes treatment.

Assessment of the potential of temporin peptides from the frog Rana temporaria (Ranidae) as anti-diabetic agents / Musale, Vishal; Casciaro, Bruno; Mangoni, Maria Luisa; Abdel-Wahab, Yasser H. A.; Flatt, Peter R.; Michael Conlon, J.. - In: JOURNAL OF PEPTIDE SCIENCE. - ISSN 1075-2617. - STAMPA. - 24:2(2018), p. e3065. [10.1002/psc.3065]

Assessment of the potential of temporin peptides from the frog Rana temporaria (Ranidae) as anti-diabetic agents

Casciaro, Bruno
Membro del Collaboration Group
;
Mangoni, Maria Luisa
Membro del Collaboration Group
;
2018

Abstract

Temporin A (FLPLIGRVLSGIL-NH2 ), temporin F (FLPLIGKVLSGIL-NH2 ), and temporin G (FFPVIGRILNGIL-NH2 ), first identified in skin secretions of the frog Rana temporaria, produced concentration-dependent stimulation of insulin release from BRIN-BD11 rat clonal β-cells at concentrations ≥1 nM, without cytotoxicity at concentrations up to 3 μM. Temporin A was the most effective. The mechanism of insulinotropic action did not involve an increase in intracellular Ca2+ concentrations. Temporins B, C, E, H, and K were either inactive or only weakly active. Temporins A, F, and G also produced a concentration-dependent stimulation of insulin release from 1.1B4 human-derived pancreatic β-cells, with temporin G being the most potent and effective, and from isolated mouse islets. The data indicate that cationicity, hydrophobicity, and the angle subtended by the charged residues in the temporin molecule are important determinants for in vitro insulinotropic activity. Temporin A and F (1 μM), but not temporin G, protected BRIN-BD11 cells against cytokine-induced apoptosis (P < 0.001) and augmented (P < 0.001) proliferation of the cells to a similar extent as glucagon-like peptide-1. Intraperitoneal injection of temporin G (75 nmol/kg body weight) together with a glucose load (18 mmol/kg body weight) in C57BL6 mice improved glucose tolerance with a concomitant increase in insulin secretion whereas temporin A and F administration was without significant effect on plasma glucose levels. The study suggests that combination therapy involving agents developed from the temporin A and G sequences may find application in Type 2 diabetes treatment.
amphibian skin peptide; anti-apoptotic peptide; insulin release; temporin; type 2 diabetes; î²-cell proliferation; structural biology; biochemistry; molecular medicine; molecular biology; pharmacology; drug discovery3003 pharmaceutical science; organic chemistry
01 Pubblicazione su rivista::01a Articolo in rivista
Assessment of the potential of temporin peptides from the frog Rana temporaria (Ranidae) as anti-diabetic agents / Musale, Vishal; Casciaro, Bruno; Mangoni, Maria Luisa; Abdel-Wahab, Yasser H. A.; Flatt, Peter R.; Michael Conlon, J.. - In: JOURNAL OF PEPTIDE SCIENCE. - ISSN 1075-2617. - STAMPA. - 24:2(2018), p. e3065. [10.1002/psc.3065]
File allegati a questo prodotto
File Dimensione Formato  
Musale_Assessment _2018.pdf

solo gestori archivio

Tipologia: Documento in Post-print (versione successiva alla peer review e accettata per la pubblicazione)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 920.83 kB
Formato Adobe PDF
920.83 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1070358
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 15
  • ???jsp.display-item.citation.isi??? 14
social impact