Differentiating effects of the glucagon-like peptide-1 analogue exendin-4 in a human neuronal cell model

Luciani, Paola; Deledda, Cristiana; Benvenuti, Stefania; Cellai, Ilaria; Squecco, Roberta; Monici, Monica; Cialdai, Francesca; Luciani, Giorgia; Danza, Giovanna; Stefano, Chiara Di; Francini, Fabio; Peri, Alessandro

doi:10.1007/s00018-010-0398-3

Cited by 44 publications

(60 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Exendin-4 induces neuronal differentiation of SH-SY5Y cells, which is accompanied by multiple cytoskeletal rearrangements and increased conductance of Na + channels and amplitude of Ca ++ currents, one of the typical characteristics of more mature neuronal cell phenotype [63]. Further, exendin-4 was reported to block oxidative stress-induced injury in SH-SY5Y cells [63].…”

Section: Role Of Glp-1-based Therapies On Diabetic Neuropathymentioning

confidence: 97%

See 1 more Smart Citation

Pleiotropic Effects of Glucagon-like Peptide-1 (GLP-1)-Based Therapies on Vascular Complications in Diabetes

Yamagishi¹,

Matsui

2011

CPD

View full text Add to dashboard Cite

Accelerated atherosclerosis and microvascular complications are the leading causes of coronary heart disease, end-stage renal failure, acquired blindness and a variety of neuropathies, which could account for disabilities and high mortality rates in patients with diabetes. Glucagon-like peptide-1 (GLP-1) belongs to the incretin hormone family. L cells in the small intestine secrete GLP-1 in response to food intake. GLP-1 not only enhances glucose-evoked insulin release from pancreatic β-cells, but also suppresses glucagon secretion from pancreatic α-cells. In addition, GLP-1 slows gastric emptying. Therefore, enhancement of GLP-1 secretion is a potential therapeutic target for the treatment of type 2 diabetes. Dipeptidyl peptidase-4 (DPP-4) is a responsible enzyme that mainly degrades GLP-1, and the half-life of circulating GLP-1 is very short. Recently, DPP-4 inhibitors and DPP-4-resistant GLP-1 receptor (GLP-1R) agonists have been developed and clinically used for the treatment of type 2 diabetes as a GLP-1-based medicine. GLP-1R is shown to exist in extra-pancreatic tissues such as vessels, kidney and heart, and could mediate the diverse biological actions of GLP-1 in a variety of tissues. So, in this paper, we review the pleiotropic effects of GLP-1-based therapies and its clinical utility in vascular complications in diabetes.

show abstract

Section: Role Of Glp-1-based Therapies On Diabetic Neuropathymentioning

confidence: 97%

“…Further, exendin-4 was reported to block oxidative stress-induced injury in SH-SY5Y cells [63]. In addition, GLP-1 has been shown to protect against neuronal cell death evoked by nerve growth factor deprivation via suppression of pro-apoptotic protein Bim [64].…”

Section: Role Of Glp-1-based Therapies On Diabetic Neuropathymentioning

confidence: 98%

Pleiotropic Effects of Glucagon-like Peptide-1 (GLP-1)-Based Therapies on Vascular Complications in Diabetes

Yamagishi¹,

Matsui

2011

CPD

View full text Add to dashboard Cite

show abstract

“…Reagents for cell cultures were from Sigma Chemical Co. (St. Louis, MO, USA). The cells were seeded in six-well plates, maintained in low serum conditions (RPMI medium with 2% FBS), and treated with exendin-4 (0.3 µM) (Sigma) for 24 and 48 h. The morphological evaluation of the differentiation of FNC and SK-N-AS cells was performed as previously reported [17]. Human mesenchymal stromal cells (hMSC) were isolated in collaboration with Dr. Riccardo Saccardi (Haematology Unit, Careggi Hospital, Florence, Italy), as described previously [19] and maintained for 24 hours in serum-free medium to obtain conditioned medium for migration assays in which we detected the release of stromal derived factor-1 (SDF1) by Quantikine ELISA Human CXCL12/SDF-1α Immunoassay (R&D systems).…”

Section: Methodsmentioning

confidence: 99%

“…NB arises from the developing sympathetic nervous system and its etiology is not clearly understood; metastatic spread of NB can happen by both lymphatic and hematogenous routes [16]. We have previously demonstrated differentiating actions of exendin-4 in NB SH-SY5Y cells, as assessed by the increasing number of neurites, changes in intracellular actin and tubulin distribution and increase of both Na + channel conductance and Ca 2+ currents (T- and L-type) amplitude, typical of a more mature neuronal phenotype [17]. In this study we investigate the effects of exendin-4 on cell adhesion, differentiation and migration, which in turn affects tumor spread and metastatization, in two NB cell lines and in human neuronal precursors, as a non-tumoral counterpart.…”

Section: Introductionmentioning

confidence: 98%

Exendin-4 Induces Cell Adhesion and Differentiation and Counteracts the Invasive Potential of Human Neuroblastoma Cells

et al. 2013

Self Cite

View full text Add to dashboard Cite

Exendin-4 is a molecule currently used, in its synthetic form exenatide, for the treatment of type 2 diabetes mellitus. Exendin-4 binds and activates the Glucagon-Like Peptide-1 Receptor (GLP-1R), thus inducing insulin release. More recently, additional biological properties have been associated to molecules that belong to the GLP-1 family. For instance, Peptide YY and Vasoactive Intestinal Peptide have been found to affect cell adhesion and migration and our previous data have shown a considerable actin cytoskeleton rearrangement after exendin-4 treatment. However, no data are currently available on the effects of exendin-4 on tumor cell motility. The aim of this study was to investigate the effects of this molecule on cell adhesion, differentiation and migration in two neuroblastoma cell lines, SH-SY5Y and SK-N-AS. We first demonstrated, by Extra Cellular Matrix cell adhesion arrays, that exendin-4 increased cell adhesion, in particular on a vitronectin substrate. Subsequently, we found that this molecule induced a more differentiated phenotype, as assessed by i) the evaluation of neurite-like protrusions in 3D cell cultures, ii) the analysis of the expression of neuronal markers and iii) electrophysiological studies. Furthermore, we demonstrated that exendin-4 reduced cell migration and counteracted anchorage-independent growth in neuroblastoma cells. Overall, these data indicate for the first time that exendin-4 may have anti-tumoral properties.

show abstract

“…В условиях in vitro эксендин-4 стимулировал пролиферацию и нейрональную дифференциацию в культуре нейрональных клеток человека [46]. Лира-глутид в условиях моделирования БА in vivo стиму-лировал нейрогенез в области зубчатой извилины гиппокампа, сопровождавшийся улучшением мел-кой моторики конечностей и пространственной па-мяти [22].…”

Section: нейрогенезunclassified

Neuroprotective properties of incretin mimetics in brain ischemia and neurodegenerative diseases

Tyurenkov¹,

Бакулин²,

Куркин³

et al. 2017

Probl Endokrinol (Mosk)

View full text Add to dashboard Cite

Волгоградский государственный медицинский университет, Волгоград, Россия Сахарный диабет 2-го типа (СД2) -заболевание, существенно увеличивающее риск нейродегенеративных заболеваний и инсульта. Значительный рост числа пациентов с СД2 на фоне старения населения определяет большой интерес к противо-диабетическим препаратам, которые, помимо гипогликемического действия, способны снижать риск сердечно-сосуди-стых и нейродегенеративных заболеваний. Согласно результатам клинических исследований, у пациентов с СД2 инкретиномиметики значительно уменьшают уро-вень гликированного гемоглобина, а также умеренно снижают артериальное давление и массу жировой ткани. Аналоги глюкагоноподобного пептида-1 (ГПП-1) при добавлении их к стандартной гипогликемической терапии значимо снижают риск сердечно-сосудистых осложнений у пациентов с СД2. Отмечается позитивное действие этих препаратов у пациентов с нейродегенеративными заболеваниями, как самостоятельными, так и возникающими на фоне СД2. В настоящее время проводятся клинические исследования влияния аналогов ГПП-1 при болезни Паркинсона и Альцгеймера. Имеющиеся данные говорят о наличии у инкретиномиметиков нейропротективных свойств, которые реализуются благо-даря присутствию рецепторов ГПП-1 на нейронах, клетках микроглии и эндотелиоцитах. Установлена способность этих рецепторов запускать важнейшие внутриклеточные сигнальные пути, поддерживающие функциональную активность клет-ки и ингибирующие апоптоз в патологических условиях. В обзоре представлены результаты исследований нейропротективных свойств препаратов с инкретиномиметическим ме-ханизмом действия. Приведены данные об их влиянии на ряд патологических процессов при нейродегенеративных за-болеваниях и нарушениях мозгового кровообращения. Показана способность инкретиномиметиков снижать активацию микроглии, выработку провоспалительных цитокинов, патологическую агрегацию белков и тормозить процессы апоптоза нейронов, а также улучшать функциональное состояние митохондрий, увеличивать экспрессию трофических факторов и стимулировать нейрогенез.Ключевые слова: cахарный диабет; инкретины; нейропротекция; нейродегенеративные заболевания; инсульт; эксенатид; лираглутид. Neuroprotective properties of incretin mimetics in brain ischemia and neurodegenerative diseases© Ivan N. Tyurenkov, Dmitry A. Bakulin, Denis V. Kurkin, Elena V. Volotova Volgograd State Medical University, Volgograd, Russia Type 2 diabetes mellitus (DMT2) is a disease significantly increasing the risk of neurodegenerative disorders and stroke. The keen interest in anti-diabetic medications, which can reduce the risk of cardiovascular and neurodegenerative disorders, is caused by the substantial rise in the number of patients with DMT2 as a result of population aging. According to the clinical trial data, incretin mimetics significantly reduce the glycosylated hemoglobin level, while moderately reducing blood pressure and adipose tissue mass in DMT2patients. When added to the conventional hypoglycemic therapy, analogues of glucagon-like peptide-1 (GLP-1) significantly dec...

show abstract

Differentiating effects of the glucagon-like peptide-1 analogue exendin-4 in a human neuronal cell model

Cited by 44 publications

References 64 publications

Pleiotropic Effects of Glucagon-like Peptide-1 (GLP-1)-Based Therapies on Vascular Complications in Diabetes

Pleiotropic Effects of Glucagon-like Peptide-1 (GLP-1)-Based Therapies on Vascular Complications in Diabetes

Exendin-4 Induces Cell Adhesion and Differentiation and Counteracts the Invasive Potential of Human Neuroblastoma Cells

Neuroprotective properties of incretin mimetics in brain ischemia and neurodegenerative diseases

Contact Info

Product

Resources

About