Agelaia MP-I: A peptide isolated from the venom of the social wasp, Agelaia pallipes pallipes, enhances insulin secretion in mice pancreatic islets

Abstract

Peptides isolated from animal venoms have shown the ability to regulate pancreatic beta cell function. Characterization of wasp venoms is important, since some components of these venoms present large molecular variability, and potential interactions with different signal transduction pathways. For example, the well studied mastoparan peptides interact with a diversity of cell types and cellular components and stimulate insulin secretion via the inhibition of ATP dependent K(+) (K(ATP)) channels, increasing intracellular Ca(2+) concentration. In this study, the insulin secretion of isolated pancreatic islets from adult Swiss mice was evaluated in the presence of synthetic Agelaia MP-I (AMP-I) peptide, and some mechanisms of action of this peptide on endocrine pancreatic function were characterized. AMP-I was manually synthesized using the Fmoc strategy, purified by RP-HPLC and analyzed using ESI-IT-TOF mass spectrometry. Isolated islets were incubated at increasing glucose concentrations (2.8, 11.1 and 22.2 mM) without (Control group: CTL) or with 10 μM AMP-I (AMP-I group). AMP-I increased insulin release at all tested glucose concentrations, when compared with CTL (P < 0.05). Since molecular analysis showed a potential role of the peptide interaction with ionic channels, insulin secretion was also analyzed in the presence of 250 μM diazoxide, a K(ATP) channel opener and 10 μM nifedipine, a Ca(2+) channel blocker. These drugs abolished insulin secretion in the CTL group in the presence of 2.8 and 11.1 mM glucose, whereas AMP-I also enhanced insulin secretory capacity, under these glucose conditions, when incubated with diazoxide and nifedipine. In conclusion, AMP-I increased beta cell secretion without interfering in K(ATP) and L-type Ca(2+) channel function, suggesting a different mechanism for this peptide, possibly by G protein interaction, due to the structural similarity of this peptide with Mastoparan-X, as obtained by modeling.

Monotreme glucagon-like peptide-1 in venom and gut: one gene – two very different functions

“…At the same time insulin releasing function of GLP-1 has to be maintained. Insulinotropic effects associated with GLP-1-like peptides have been reported in a range of venomous species including arthropods, reptiles3233343536, and recently in cone snail venom, which induces severe hypoglycemic shock in its fish prey16. In contrast to the evolution of Gcg -like genes and insulin mimetics in other species, monotremes are the first examples of species that have recruited the endogenous GLP-1 system into venom.…”

Differential Properties of Venom Peptides and Proteins in Solitary vs. Social Hunting Wasps

“…Meanwhile, MCD by mastoparan may occur also through the exocytosis of granules, triggered by mastoparan modulating G-protein activity without receptor interaction [ 112 ]. The net effect of MCD depends on the cell types: the secretion of histamine from mast cells, serotonin from the platelets, catecholamines from chromaffin cells, prolactin from the anterior pituitary, and even insulin from pancreatic β-cells [ 51 , 110 , 113 ]. Cell lytic activity also varies depending on the cell types.…”

“…Mastoparan or mastoparan-like peptides are the alpha-helical peptides and have been identified in a wide range of wasps, including both solitary and social wasps [ 16 , 18 , 19 , 20 , 27 , 28 , 29 , 30 , 31 , 32 , 38 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ]. The AMP from the Brazilian wasp P. paulista venom (MP1) has a broad-spectrum antibiotic activity against Gram-negative and Gram-positive bacteria without showing apparent hemolytic and cytotoxic activities [ 42 ].…”

“…, pompilidotoxin and dendrotoxin-like peptide) are known to be involved in prey paralysis ( Table 1 and Table 2 ; [ 16 , 18 , 23 , 77 , 78 , 138 , 139 ]). However, only one venom component that can regulate prey physiology has been identified and characterized in solitary wasps [ 16 , 18 , 51 , 84 ]. Nevertheless, given that solitary hunting wasps are also in need of the long-term metabolic alteration and developmental arrest of prey to provide fresh provisions to their progeny, a more versatile array of physiology-manipulating components is likely to be present in the venom of solitary wasps.…”

Antimycobacterial Activity of a New Peptide Polydim-I Isolated from Neotropical Social Wasp Polybia dimorpha

“…Wasp venoms primarily comprise peptides, including AMP, which are responsible for most of the biological activities of this poison. Among those peptides, the most recurrent are those from the class of mastoparans [ 16 – 18 ], small cationic and amphiphilic alpha-helical peptides that possess high affinity to negatively charged biological membranes. Thus, the venom of social wasps has great potential for the study of new antimicrobials, particularly with respect to antimycobacterial activity.…”