Tigerinin-1R: a potent, non-toxic insulin-releasing peptide isolated from the skin of the Asian frog, Hoplobatrachus rugulosus

Ojo, Opeolu O.; Abdel-Wahab, Yasser; Flatt, Peter R.; Mechkarska, Milena; Conlon, J. Michael

doi:10.1111/j.1463-1326.2011.01470.x

Cited by 43 publications

(46 citation statements)

References 29 publications

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“…Cell culture assay medium was removed and the cells were exposed to 300 μM and 600 μM MG for 8 h. Intracellular Ca 2+ responses and membrane potential were monitored using FlexStation scanning fluorimeter with integrated fluid transfer workstation (Ojo et al . ).…”

Section: Methodsmentioning

confidence: 97%

“…5 9 10 4 cells/well were seeded in Laminin pre-coated clear bottom 96 well black plates for 24 h and pre-treated for 4 h with different concentrations of Liraglutide. Cell culture assay medium was removed and the cells were exposed to 300 lM and 600 lM MG for 8 h. Intracellular Ca 2+ responses and membrane potential were monitored using FlexStation scanning fluorimeter with integrated fluid transfer workstation (Ojo et al 2011).…”

Section: Measurement Of Total Intracellular Calcium and Membrane Potementioning

confidence: 99%

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Neuroprotective and anti‐apoptotic effects of liraglutide on SH‐SY5Y cells exposed to methylglyoxal stress

Sharma

Jalewa

Hölscher

2013

Journal of Neurochemistry

129

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Glucagon-like peptide 1 (GLP-1) is a growth factor that has demonstrated neuroprotective properties in a range of studies.In an APPswe/PS1ΔE9 mouse model of Alzheimer's disease (AD), we previously found protective effects on memory formation, synaptic plasticity, synapse survival and a reduction of amyloid synthesis and plaque load in the brain. Here, we analyse the neuroprotective properties of the GLP-1 analogue liraglutide in human neuroblastoma cell line SH-SY5Y during methyl glyoxal stress. We show for the first time that cell viability was enhanced by liraglutide (XTT assay) in a dosedependent way, while cytotoxicity (LDH assay) and apoptosis were reduced. Expression of the pro-survival Mcl1 signaling protein was increased, as was activation of cell survival kinases Akt, MEK1/2 and the transcription factor p90RSK. Liraglutide also decreased pro-apoptotic Bax and Bik expression. In addition, the membrane potential and the influx of calcium into the cell were enhanced by liraglutide. GLP-1 receptor expression was also increased by the drug. The results demonstrate a range of growth factor-related cytoprotective processes induced by liraglutide, which is currently on the market as a treatment for type 2 diabetes (Victozaâ). It is also tested in clinical trials in patients with Alzheimer disease.

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Section: Methodsmentioning

confidence: 97%

Section: Measurement Of Total Intracellular Calcium and Membrane Potementioning

confidence: 99%

Neuroprotective and anti‐apoptotic effects of liraglutide on SH‐SY5Y cells exposed to methylglyoxal stress

Sharma

Jalewa

Hölscher

2013

Journal of Neurochemistry

129

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“…Cells used for the experiments were between passages 25 and 40. Palmitic acid sodium salt (Sigma, Poole, Dorset, UK) was dissolved in 50% ethanol and coupled to 5% fatty acid-free bovine serum albumin (BSA) (Sigma, Poole, Dorset, UK) at 37 ° C for 1 h. The viability of cells after palmitate treatment was assessed by MTT assay or release of LDH (CytoTox 96 non-radioactive cytotoxicity assay kit, Promega, UK) (Mosmann , 1983 ;Ojo et al , 2011 ) .…”

Section: Cell Culture and Viabilitymentioning

confidence: 99%

Effects of lipotoxicity on a novel insulin-secreting human pancreatic β-cell line, 1.1B4

Vasu

McClenaghan²,

McCluskey³

et al. 2013

Biological Chemistry

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The novel insulin-secreting human pancreatic β-cell line, 1.1B4, demonstrates stability in culture and many of the secretory functional attributes of human pancreatic β-cells. This study investigated the cellular responses of 1.1B4 cells to lipotoxicity. Chronic 18-h exposure of 1.1B4 cells to 0.5 mm palmitate resulted in decreased cell viability and insulin content. Secretory responses to classical insulinotropic agents and cellular Ca2+ handling were also impaired. Palmitate decreased glucokinase activity and mRNA expression of genes involved in secretory function but up-regulated mRNA expression of HSPA5, EIF2A, and EIF2AK3, implicating activation of the endoplasmic reticulum stress response. Palmitate also induced DNA damage and apoptosis of 1.1B4 cells. These responses were accompanied by increased gene expression of the antioxidant enzymes SOD1, SOD2, CAT and GPX1. This study details molecular mechanisms underlying lipotoxicity in 1.1B4 cells and indicates the potential value of the novel β-cell line for future research.

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“…Thus, the need for new insulinotropic and euglycemic agents to assist insulin therapy in diabetic treatment is urgent. Amphibian skin secretions, especially those of frogs, are known to contain insulinotropic compounds . In our previous work, skin secretions from odorous frogs, which are characterized by their unpleasant skin exudates when stimulated, were found to have insulinotropic, antimicrobial, antioxidant, and immunomodulatory activities .…”

Section: Discussionmentioning

confidence: 94%

Characterization of an insulinotropic peptide from skin secretions of Odorrana andersonii

Shang

Yang

et al. 2017

J. Pept. Sci.

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Insulinotropic peptide agents are regarded as potential candidates for anti-diabetic treatment. In the present study, a novel insulinotropic peptide, termed OA-A1, was purified from frog skin secretions of Odorrana andersonii. Mature OA-A1 was determined to be a 1965.049 Da peptide with an amino acid sequence of LVGKLLKGAVGDVCGLLPIC, in which an intramolecular disulfide bridge was formed by two cysteine residues. At the cellular level, OA-A1 exhibited potent proliferation promoting effects on mouse-derived pancreatic β-TC-6 cells and significantly stimulated insulin release in β-TC-6 cells at a minimum concentration of 1 nM. In the animal model, OA-A1 also showed a dose-dependent insulin-releasing role in mice. At concentrations ranging from 1 nmol/kg to 1 μmol/kg, OA-A1 had a significant acute hypoglycemic effect on streptozotocin (STZ)-induced diabetic mice. The pancreatic islet areas of diabetic mice increased dose-dependently after 21 days of OA-A1 treatment (1-100 nmol/kg) compared with those of the saline control group. Moreover, OA-A1 significantly improved the oral glucose tolerance of STZ-induced diabetic mice. Taken together, these results suggest that OA-A1 provides an excellent template for the development of novel anti-diabetic therapeutic agents. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

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Tigerinin-1R: a potent, non-toxic insulin-releasing peptide isolated from the skin of the Asian frog, Hoplobatrachus rugulosus

Abstract: Tigerinin-1R is a potent, non-toxic insulin-releasing peptide that shows potential for development into an agent for the treatment of type 2 diabetes.

Cited by 43 publications

References 29 publications

Neuroprotective and anti‐apoptotic effects of liraglutide on SH‐SY5Y cells exposed to methylglyoxal stress

Neuroprotective and anti‐apoptotic effects of liraglutide on SH‐SY5Y cells exposed to methylglyoxal stress

Effects of lipotoxicity on a novel insulin-secreting human pancreatic β-cell line, 1.1B4

Characterization of an insulinotropic peptide from skin secretions of Odorrana andersonii

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