Magainin-AM2 improves glucose homeostasis and beta cell function in high-fat fed mice

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

doi:10.1016/j.bbagen.2014.10.011

Cited by 21 publications

(12 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This was associated with improved glucose tolerance following oral and intraperitoneal glucose administration accompanied by enhanced insulin secretion. These observations are broadly consistent with effects of tigerinin-1R [ 12 ], [I10W]-tigerinin-1R [ 30 ] and magainin-AM2 [ 13 ], suggesting a possible similar spectrum of actions in this animal model of obesity and diabetes. We have previously shown that the antidiabetic effects of magainin-AM2 [ 13 ] and [I10W]-tigerinin-1R [ 30 ] were accompanied by improvement in insulin sensitivity.…”

Section: Discussionsupporting

confidence: 81%

“…Pancreatic tissues were homogenized in 20 mM Tris-HCl, 150 mM NaCl, 1 mM EDTA, 1 mM EGTA and 0.5% Triton X 100; pH 7.5 as previously described [ 14 ]. Blood samples (approximately 150 μl), collected from the cut tip of the tail vein of unanesthetized mice at intervals indicated in the Figures were used for blood glucose measurements and determination of plasma insulin as previously described [ 13 , 14 ]. Blood glucose was measured using a hand-held Ascencia Contour meter (Bayer Healthcare, UK).…”

Section: Methodsmentioning

confidence: 99%

“…The high fat fed mouse exhibits obesity, glucose intolerance and insulin resistance and so is a useful model for a preliminary investigation of the therapeutic potential of peptides in treatment of patients with type 2 diabetes [ 11 ]. More recently, it has been shown that twice daily treatment of high-fat fed mice for up to 28 days with tigerinin-1R [ 12 ], magainin-AM1 [ 13 ], and CPF-SE1 [ 14 ] results in an improvement in glucose tolerance, insulin sensitivity, and islet β-cell secretory responsiveness.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2015

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 81%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2015

View full text Add to dashboard Cite

show abstract

“…The relative short-term of our analyses (75 d) could account for the lack of significant results. Studies usually report protocols of high-fat diet regimens using time courses of 8-12 weeks (56-84 d) to observe effects on lipid deposition and weight gain (8)(9)(10) . Furthermore, we have not used a high-fat diet but rather citrate supplementation, which despite the fact that it did not alter lipid deposition promoted significant effects on other metabolic markers.…”

Section: Discussionmentioning

confidence: 99%

Exogenous citrate impairs glucose tolerance and promotes visceral adipose tissue inflammation in mice

et al. 2016

View full text Add to dashboard Cite

Overweight and obesity have become epidemic worldwide and are linked to sedentary lifestyle and the consumption of processed foods and drinks. Citrate is a metabolite that plays central roles in carbohydrate and lipid metabolism. In addition, citrate is the additive most commonly used by the food industry, and therefore is highly consumed. Extracellular citrate can freely enter the cells via the constitutively expressed plasma membrane citrate transporter. Within the cytosol, citrate is readily metabolised by ATP-citrate lyase into acetyl-CoA -the metabolic precursor of endogenously produced lipids and cholesterol. We therefore hypothesised that the citrate ingested from processed foods and drinks could contribute to increased postprandial fat production and weight gain. To test our hypothesis, we administered citrate to mice through their drinking water with or without sucrose and monitored their weight gain and other metabolic parameters. Our results showed that mice receiving citrate or citrate + sucrose did not show increased weight gain or an increase in the weight of the liver, skeletal muscles or adipose tissues (AT). Moreover, the plasma lipid profiles (TAG, total cholesterol, LDL and HDL) were similar across all groups. However, the group receiving citrate + sucrose showed augmented fasting glycaemia, glucose intolerance and the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-10) in their AT. Therefore, our results suggest that citrate consumption contributes to increased AT inflammation and altered glucose metabolism, which is indicative of initial insulin resistance. Thus, citrate consumption could be a previously unknown causative agent for the complications associated with obesity.Key words: Citrate: Obesity: Inflammation: Food additives: Insulin resistance: Diabetes Overweight and obesity are currently a threat to public health. The number of overweight and obese individuals has more than doubled since 1980, and it is estimated that 39 % of the world population is overweight and 13 % are obese (1,2) . This epidemic is largely attributed to the modern sedentary lifestyle and a 'westernised' diet, based on the consumption of caloric and processed foods and drinks. In that sense, much attention has been given to the contribution of the high fat and high sugar contents of modern food (3) . Meanwhile, the relative contribution of food additives has been largely ignored, possibly because of their negligible energy content and the assumption that food additives are metabolically inert.Citrate is the most widely used additive in the food industry, as it is a very efficient food flavouring agent and preservative (4) . Citrate has been considered innocuous, despite the fact that it is a very important metabolite in virtually all cell types. Citrate is produced in the mitochondria in the first reaction of the Krebs cycle through the condensation of one acetyl-CoA and one oxaloacetate molecule. In a situation of excess energy (postprandially), citrate accumulates and is then expo...

show abstract

“…In addition, complex arrays of peptides with varying degrees of cytotoxic activity against bacteria, fungi, protozoa, and viruses are found in skin secretions of these frogs, and examples include the dermaseptins, dermatoxins, plasticins, phylloseptins, and phylloxins . Although originally termed “antimicrobial peptides” and considered to be a frontline defense against pathogenic microorganisms in the environment, such peptides are multifunctional and also display immunomodulatory properties, stimulate insulin release from clonal β cells, and show selective cytotoxicity against tumor cells and are therefore better described by the more general term “host‐defense peptides.”…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory, insulinotropic, and cytotoxic activities of phylloseptins and plasticin‐TR from the Trinidanian leaf frogPhyllomedusa trinitatis

Pantic

Guilhaudis

Musale

et al. 2019

Journal of Peptide Science

View full text Add to dashboard Cite

The aim of the study was to determine the in vitro immunomodulatory, cytotoxic, and insulin‐releasing activities of seven phylloseptin‐TR peptides and plasticin‐TR, first isolated from the frog Phyllomedusa trinitatis. The most cationic peptides, phylloseptin‐1.1TR and phylloseptin‐3.1TR, showed greatest cytotoxic potency against A549, MDA‐MB231, and HT‐29 human tumor‐derived cells and against mouse erythrocytes. Phylloseptin‐4TR was the most hydrophobic and the most effective peptide at inhibiting production of the proinflammatory cytokines TNF‐α and IL‐1β by mouse peritoneal cells but was without effect on production of the antiinflammatory cytokine IL‐10. Phylloseptin‐2.1TR and phylloseptin‐3.3TR were the most effective at stimulating the production of IL‐10. The noncytotoxic peptide, plasticin‐TR, inhibited production of TNF‐α and IL‐1β but was without effect on IL‐10 production. The results of CD spectroscopy suggest that the different properties of plasticin‐TR compared with the immunostimulatory activities of the previously characterized plasticin‐L1 from Leptodactylus laticeps may arise from greater ability of plasticin‐TR to oligomerize and adopt a stable helical conformation in a membrane‐mimetic environment. All peptides stimulated release of insulin from BRIN‐BD11 rat clonal β cells with phylloseptin‐3.2TR being the most potent and effective and phylloseptin‐2.1TR the least effective suggesting that insulinotropic potency correlates inversely with helicity. The study has provided insight into structure‐activity relationships among the phylloseptins. The combination of immunomodulatory and insulinotropic activities together with low cytotoxicity suggests that phylloseptin‐3.3TR and plasticin‐TR may represent templates for the development of agents for use in antiinflammatory and type 2 diabetes therapies.

show abstract

Magainin-AM2 improves glucose homeostasis and beta cell function in high-fat fed mice

Cited by 21 publications

References 33 publications

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

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

Exogenous citrate impairs glucose tolerance and promotes visceral adipose tissue inflammation in mice

Immunomodulatory, insulinotropic, and cytotoxic activities of phylloseptins and plasticin‐TR from the Trinidanian leaf frogPhyllomedusa trinitatis

Contact Info

Product

Resources

About