Insulin Releasing Properties of the Temporin Family of Antimicrobial Peptides

Abdel-Wahab, Yasser; Marenah, Lamin; Flatt, Peter R.; Conlon, J. Michael

doi:10.2174/092986607781483822

Cited by 38 publications

(8 citation statements)

References 24 publications

(26 reference statements)

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“…Glycation is a common post translational modification of proteins in diabetes and is strongly implicated in the genesis of long-term complications [ 42 ]. Insulin glycation is an example of glycation of short-lived protein that can lead to insulin resistance because of its reduced biological activity [ 43 ]. In our study, A. squamosa inhibited the insulin glycation in vitro, suggesting its utility in helping to prevent glycation of functional and structural proteins in the progression of insulin resistance and diabetic complications.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Antidiabetic and Insulin Releasing Effects of A. squamosa, Including Isolation and Characterization of Active Phytochemicals

Ansari

Flatt

Harriott

et al. 2020

Plants

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Annona squamosa is generally referred to as a ‘custard apple’. Antidiabetic actions of hot water extract of Annona squamosa (HWAS) leaves together with isolation of active insulinotropic compounds were studied. Insulin release, membrane potential and intracellular Ca2+ were determined using BRIN-BD11 cells and isolated mouse islets. 3T3L1 adipocytes and in vitro models were used to determine cellular glucose uptake, insulin action, starch digestion, glucose diffusion, DPP-IV activity and glycation. Glucose intolerant high-fat fed rats were used for in vivo studies. Active compounds were isolated and characterized by HPLC, LCMS and NMR. HWAS stimulated insulin release from clonal β-cells and mouse islets. Using fluorescent indicator dyes and modulators of insulin secretion, effects could be attributed to depolarization of β-cells and influx of Ca2+. Secretion was stimulated by isobutylmethylxanthine (IBMX), tolbutamide or 30 mM KCl, indicating additional non-KATP dependent pathways. Extract stimulated cellular glucose uptake and insulin action and inhibited starch digestion, protein glycation, DPP-IV enzyme activity and glucose diffusion. Oral HWAS improved glucose tolerance and plasma insulin in high-fat fed obese rats. Treatment for 9 days with HWAS (250 mg/5 mL/kg), partially normalised energy intake, body weight, pancreatic insulin content, and both islet size and beta cell mass. This was associated with improved oral glucose tolerance, increased plasma insulin and inhibition of plasma DPP-IV activity. Isolated insulinotropic compounds, including rutin (C27H30O16), recapitulated the positive actions of HWAS on beta cells and in vivo glucose tolerance and plasma insulin responses. Annona squamosa is attractive as a dietary adjunct in treatment of T2DM and as a source of potential antidiabetic agents including rutin.

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Section: Discussionmentioning

confidence: 99%

Evaluation of the Antidiabetic and Insulin Releasing Effects of A. squamosa, Including Isolation and Characterization of Active Phytochemicals

Ansari

Flatt

Harriott

et al. 2020

Plants

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“…Two analogs of GLP-1, exenatide and liraglutide, have been successfully applied to clinical practice to the benefit of thousands of diabetic patients [ 15 , 29 , 30 ]. Moreover, skin secretions of anurans as a natural peptide library have yielded a variety of peptide candidates, among which several agents have been shown to have the ability to promote insulin release [ 16 , 17 , 18 , 19 , 20 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…In addition to these peptides, skin secretions of anurans as a natural peptide library have recently received increasing attention [ 16 , 17 ]. Several peptides, such as temporin-Vb [ 18 ], esculentins-1, esculentins-1B, brevinins-1E, and brevinins-2EC [ 19 ], which were isolated as antimicrobial agents, were shown to promote the secretion of insulin in vitro or in vivo. However, peptides such as tigerinin-1R [ 20 ] and alyteserin-2a [ 21 ], which are partially deficient in antimicrobial activity, are able to promote the secretion of insulin, showing a potential for use in the treatment to type 2 diabetes.…”

Section: Introductionmentioning

confidence: 99%

Role of Disulfide Bonds in Activity and Stability of Tigerinin-1R

Chen

Huang

et al. 2018

IJMS

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Tigerinin-1R (Arg–Val–Cys–Ser–Ala–Ile–Pro–Leu–Pro–Ile–Cys–His–NH2), a cationic 12-mer peptide containing a disulfide bond extracted from frog skin secretions, lacks antibacterial activity, but has the ability to stimulate insulin release both in vitro and in vivo. To study the structure–function relationships of tigerinin-1R, we designed and synthesized five analogs, including tigerinin-cyclic, tigerinin-1R-L4, tigerinin-linear, [C3K]tigerinin-1R, and [C11K]tigerinin-1R. Tigerinin-1R promoted insulin secretion in a concentration-dependent manner in INS-1 cells without obvious cytotoxicity. At a concentration of 10−5 M, [C11K]tigerinin-1R exhibited the highest stimulation ability, suggesting that the positive charge at the C-terminus may contribute to the in vitro insulin-releasing activity of tigerinin-1R. Tigerinin-1R peptides stimulated insulin release in INS-1 cells through a universal mechanism that involves mobilization of intracellular calcium without disrupting the cell membrane. In vivo experiments showed that both tigerinin-1R and [C11K]tigerinin-1R improved glucose tolerance in overnight-fasted mice. Due to its structural stability, tigerinin-1R showed superior hypoglycemic activity to [C11K]tigerinin-1R, which suggested a critical role of the disulfide bonds. In addition, we also identified a protective effect of tigerinin-1R peptides in apoptosis induced by oxidative stress. These results further confirm the potential for the development of tigerinin-1R as an anti-diabetic therapeutic agent in clinical practice.

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“…PLA 2 from snake venoms and α-LTX from black widow spider venoms) and the glucagon superfamily peptides. Brevinins are a family of antimicrobial peptides with the length of 24-amino acids initially isolated from the skin of Rana brevipoda porsa [ 29 ], and are found to have insulin-releasing activity [ 14 , 16 ]. Temporins are also a large family of antimicrobial peptides with 13-residues firstly identified in the European red frog Rana temporaria [ 11 ], and other members were subsequently discovered in several North America Rana species, including R. clamitans, R. luteiventris, R. pipiens, R. grylio, and A. loloensis and R. palustris [ 18 , 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…As the work of isolating novel insulinotropic peptides and characterizing the insulin-releasing activity of known bioactive peptides are focused on, several new insulinotropic peptides have been isolated from skin secretions of amphibian [ 13 – 16 ]. Simultaneously, due to our previous study, the skin secretions of frog Amolops loloensis comprised multiple kinds of biologically active polypeptides, including bradykinin-like peptide [ 17 ], antibacterial peptides [ 18 ] and algesic peptides [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

A Novel Insulinotropic Peptide from the Skin Secretions of Amolops loloensis Frog

Bai

et al. 2014

Nat. Prod. Bioprospect.

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Various kinds of biologically active peptides have previously been isolated from the skin secretions of Amolops loloensis frog, such as antimicrobial peptides, bradykinin-like peptides and algesic peptides. A novel insulinotropic peptide named amolopin was identified in A. loloensis frog’s skin secretion. Its primary structure sequence was determined by Edman degradation as: FLPIVGKSLSGLSGKL-NH2. BLAST search indicates that the amino acid sequence of amolopin is quite different from other known insulin secretagogues, including mastoparan, exendins and α-latrotoxin, nor does it like incretins (e.g. glucagons like peptide-1 and glucose-dependent insulinotropic ploypeptide) either. However, amolopin shows certain structural similarity with amphibian antimicrobial temporins and vespid chemotactic peptides isolated from Vespa magnifica. Amolopin can stimulate insulin release in INS-1 cells in a dose-dependent manner. Primary investigation on its action mechanisms reveals that amolopin does not increase the influx of Ca2+. In conclusion, a novel 16-amino acid peptide with insulin-releasing activity is initially discovered from the skin secretion of A. loloensis frog. Further work is necessary to evaluate its potential as novel anti-diabetic candidate.

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Insulin Releasing Properties of the Temporin Family of Antimicrobial Peptides

Cited by 38 publications

References 24 publications

Evaluation of the Antidiabetic and Insulin Releasing Effects of A. squamosa, Including Isolation and Characterization of Active Phytochemicals

Evaluation of the Antidiabetic and Insulin Releasing Effects of A. squamosa, Including Isolation and Characterization of Active Phytochemicals

Role of Disulfide Bonds in Activity and Stability of Tigerinin-1R

A Novel Insulinotropic Peptide from the Skin Secretions of Amolops loloensis Frog

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