Insulin-releasing and cytotoxic properties of the frog skin peptide, tigerinin-1R: a structure–activity study

Srinivasan, Dhanalakshmi; Ojo, Opeolu O.; Abdel-Wahab, Yasser; Flatt, Peter R.; Guilhaudis, Laure; Conlon, J. Michael

doi:10.1016/j.peptides.2014.02.002

Cited by 25 publications

(30 citation statements)

References 39 publications

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“…The significant reduction in the stimulatory effects of the plant extract in the presence of verapamil or diazoxide strongly suggests that the insulin-releasing effects of the plant extract are mediated partly via the K ATP -dependent pathway. Similar inhibition of insulinotropic effects have been reported for some plant extracts[21] and some recently identified novel insulin-releasing amphibian host defence peptides[15,22].Increased membrane potential is a key feature of the K ATP -dependent pathway of insulin secretion[23]. The binding of an insulinotropic agent (such as glibenclamide, a sulphonyureas) to the ATP-dependent K + channel on beta cell membranes inhibits the hyperpolarizing outflow of potassium, resulting in membrane depolarization[24].Though the identification of the specific binding site of the active component of the acetone extract of M. oleifera is beyond the scope of the present study, investigations conducted in this study revealed that the plant extract significantly induced membrane depolarization in BRIN-BD11 cells.…”

supporting

confidence: 75%

Insulinotropic actions of Moringa oleifera involves the induction of membrane depolarization and enhancement of intracellular calcium concentration

Ojo¹,

Ojo²

2015

J Exp Integr Med

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Objective: Moringaoleifera extracts have been widely reported for its insulinotropic and other antidiabetic effects. However, mechanisms behind the insulinotropic actions of M. oleiferaextracts are not well understood. This study investigated the mechanism underlying the insulinotropic actions of acetone extract of M. oleifera Method: Phytochemical composition of M. oleifera extracts was determined using standard procedures. Total flavonoid and total phenolic compounds in the extract were also quantified. Effects of the extracts on glucose stimulated insulin secretion (GSIS), membrane depolarization and intracellular calcium concentration using BRIN-BD11 clonal pancreatic beta cells. Results: Resultsobtained showed the preponderance of alkaloids, flavonoids, glycosides, phenols, saponins and tannins in the extract. Total flavonoids and phenolic contents of the extract were estimated as 25.23±0.57mgQE/g and 54.26±1.89 mgGE/g respectively. The glucose dependent insulinotropic effects of the extract were significantly inhibited in the presence of diazoxide (48%, P<0.001) or verapamil (35%, P<0.001) and in the absence of extracellular calcium (47%, P<0.001). Co-incubation of cells with the extract and IBMX or tolbutamide increased insulin secretion by 2-fold while a 1.2-fold (P<0.05) increase was observed in cells depolarized with KCl (30mM)in the presence of the plant extract. The extract significantly induced membrane depolarization (7.1-fold, P<0.001) and enhanced intracellular calcium concentration (2.6-fold, P<0.01) in BRIN-BD11 cells. Conclusion: These observations suggest that the insulinotropic actions of acetone extract of M. oleifera may be mediated via the K ATP-dependent pathway of insulin release.

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supporting

confidence: 75%

Insulinotropic actions of Moringa oleifera involves the induction of membrane depolarization and enhancement of intracellular calcium concentration

Ojo¹,

Ojo²

2015

J Exp Integr Med

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“…Tigerinins, first reported in H. tigerinus , [ 83 ] are a family of 4 peptides identified in H. rugulosus that are characterized by potent antimicrobial activity against gram-positive bacteria (MICs: 20–50 µg/mL) and gram-negative bacteria (MICs: 20–100 µg/mL) ( Table 1 and Table 2 ). Tigerinins isolated from H. rugulosus have also been found to stimulate insulin release from rat BRIN-BD11 clonal β cell line [ 84 , 85 ]. Ojo et al .…”

Section: Diversity Of Hdps Found In the Skin Secretion Of Asian Frmentioning

confidence: 99%

Host Defense Peptides from Asian Frogs as Potential Clinical Therapies

et al. 2015

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Host defense peptides (HDPs) are currently major focal points of medical research as infectious microbes are gaining resistance to existing drugs. They are effective against multi-drug resistant pathogens due to their unique primary target, biological membranes, and their peculiar mode of action. Even though HDPs from 60 Asian frog species belonging to 15 genera have been characterized, research into these peptides is at a very early stage. The purpose of this review is to showcase the status of peptide research in Asia. Here we provide a summary of HDPs from Asian frogs.

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“…We have demonstrated previously in studies using the amphibian peptides pseudin-2 [ 15 ], B2RP [ 27 ], alyteserin-2a [ 28 ] and tigerinin-1R [ 29 ] that site-specific amino acid substitutions that result in increasing cationicity may lead to significant enhancement of their in vitro insulin releasing actions. In this study, such amino acid substitutions resulted in increased net charge and isoelectric point ( Table 1 ) as well as enhanced insulinotropic potency.…”

Section: Discussionmentioning

confidence: 99%

Esculentin-2CHa-Related Peptides Modulate Islet Cell Function and Improve Glucose Tolerance in Mice with Diet-Induced Obesity and Insulin Resistance

et al. 2015

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The frog skin host-defense peptide esculentin-2CHa (GFSSIFRGVA10KFASKGLGK D20LAKLGVDLVA30CKISKQC) displays antimicrobial, antitumor, and immunomodulatory properties. This study investigated the antidiabetic actions of the peptide and selected analogues. Esculentin-2CHa stimulated insulin secretion from rat BRIN-BD11 clonal pancreatic β-cells at concentrations greater than 0.3 nM without cytotoxicity by a mechanism involving membrane depolarization and increase of intracellular Ca2+. Insulinotropic activity was attenuated by activation of KATP channels, inhibition of voltage-dependent Ca2+ channels and chelation of extracellular Ca2+. The [L21K], [L24K], [D20K, D27K] and [C31S,C37S] analogues were more potent but less effective than esculentin-2CHa whereas the [L28K] and [C31K] analogues were both more potent and produced a significantly (P < 0.001) greater maximum response. Acute administration of [L28K]esculentin-2CHa (75 nmol/kg body weight) to high fat fed mice with obesity and insulin resistance enhanced glucose tolerance and insulin secretion. Twice-daily administration of this dose of [L28K]esculentin-2CHa for 28 days had no significant effect on body weight, food intake, indirect calorimetry or body composition. However, mice exhibited decreased non-fasting plasma glucose (P < 0.05), increased non-fasting plasma insulin (P < 0.05) as well as improved glucose tolerance and insulin secretion (P < 0.01) following both oral and intraperitoneal glucose loads. Impaired responses of isolated islets from high fat fed mice to established insulin secretagogues were restored by [L28K]esculentin-2CHa treatment. Peptide treatment was accompanied by significantly lower plasma and pancreatic glucagon levels and normalization of α-cell mass. Circulating triglyceride concentrations were decreased but plasma cholesterol and LDL concentrations were not significantly affected. The data encourage further investigation of the potential of esculentin-2CHa related peptides for treatment of patients with type 2 diabetes.

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Insulin-releasing and cytotoxic properties of the frog skin peptide, tigerinin-1R: a structure–activity study

Cited by 25 publications

References 39 publications

Insulinotropic actions of Moringa oleifera involves the induction of membrane depolarization and enhancement of intracellular calcium concentration

Insulinotropic actions of Moringa oleifera involves the induction of membrane depolarization and enhancement of intracellular calcium concentration

Host Defense Peptides from Asian Frogs as Potential Clinical Therapies

Esculentin-2CHa-Related Peptides Modulate Islet Cell Function and Improve Glucose Tolerance in Mice with Diet-Induced Obesity and Insulin Resistance

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