Repeated administration of exendin-4 reduces focal cerebral ischemia-induced infarction in rats

Briyal, Seema; Gulati, Kartike; Gulati, Anil

doi:10.1016/j.brainres.2011.10.026

Cited by 62 publications

(68 citation statements)

References 69 publications

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“…Pre‐stroke treatment with ICV‐administered exendin‐4 or peripherally‐administered alogliptin effectively reduced neurological deficits and infarct volume in normoglycemic rodents112, 113. Post‐stroke treatment with peripherally‐administered exendin‐4 or liraglutide also showed protection against motor impairment, and led to reduction of infarct volume in normoglycemic rodents114, 115.…”

Section: Type 2 Diabetes Mellitus Stroke and Incretin‐based Therapiesmentioning

confidence: 98%

Potentials of incretin‐based therapies in dementia and stroke in type 2 diabetes mellitus

Groeneveld

Kappelle

Biessels

2015

J of Diabetes Invest

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Patients with type 2 diabetes mellitus are at risk for accelerated cognitive decline and dementia. Furthermore, their risk of stroke is increased and their outcome after stroke is worse than in those without diabetes. Incretin‐based therapies are a class of antidiabetic agents that are of interest in relation to these cerebral complications of diabetes. Two classes of incretin‐based therapies are currently available: the glucagon‐like‐peptide‐1 agonists and the dipeptidyl peptidase‐4 ‐inhibitors. Independent of their glucose‐lowering effects, incretin‐based therapies might also have direct or indirect beneficial effects on the brain. In the present review, we discuss the potential of incretin‐based therapies in relation to dementia, in particular Alzheimer's disease, and stroke in patients with type 2 diabetes. Experimental studies on Alzheimer's disease have found beneficial effects of incretin‐based therapies on cognition, synaptic plasticity and metabolism of amyloid‐β and microtubule‐associated protein tau. Preclinical studies on incretin‐based therapies in stroke have shown an improved functional outcome, a reduction of infarct volume as well as neuroprotective and neurotrophic properties. Both with regard to the treatment of Alzheimer's disease, and with regard to prevention and treatment of stroke, randomized controlled trials in patients with or without diabetes are underway. In conclusion, experimental studies show promising results of incretin‐based therapies at improving the outcome of Alzheimer's disease and stroke through glucose‐independent pleiotropic effects on the brain. If these findings would indeed be confirmed in large clinical randomized controlled trials, this would have substantial impact.

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Section: Type 2 Diabetes Mellitus Stroke and Incretin‐based Therapiesmentioning

confidence: 98%

Potentials of incretin‐based therapies in dementia and stroke in type 2 diabetes mellitus

Groeneveld

Kappelle

Biessels

2015

J of Diabetes Invest

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“…Существует ряд работ, в которых продемонстриро-вано защитное действие ГПП-1 в условиях транзиторной фокальной ишемии головного мозга у животных [21][22][23][24][25][26].…”

Section: нейропротективное действие инкретиномиметиковunclassified

“…В работе S. Briyal проводилось исследование влия-ния длительного применения эксендина-4 перед ишемией головного мозга крыс на объем инфаркта, вы-раженность неврологического дефицита, а также пара-метры оксидативного стресса [22]. Оценивались такие показатели, как уровень малонового диальдегида, вос-становленного глутатиона и супероксиддисмутазы.…”

Section: антиоксидантное и противовоспалительное действиеunclassified

“…Изменений в экспрессии эндотелино-вых рецепторов типа В после инсульта не было. Таким образом, S. Briyal еще раз подтвердил, что эксендин-4 как агонист рецептора ГПП-1 оказывает нейропро-тективный эффект при инсульте путем уменьшения оксидативного стресса, и доказал, что его влияние не связано с воздействием на эндотелиновый рецеп-тор [22].…”

Section: антиоксидантное и противовоспалительное действиеunclassified

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Mechanisms of neuroprotective action of incretin mimetics

Власов¹,

Симаненкова²,

Дора³

et al. 2016

Diabetes mellitus

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1/2016 © Сахарный диабет, 2016Вопросы патогенеза ахарный диабет 2 типа (СД2) является одной из ве-дущих проблем современного здравоохранения. Количество больных СД постоянно прогрессивно увеличивается. По оценке Международной Диабетической Федерации, в 2014 г. число взрослых больных СД на планете составило более 387 млн человек, порядка 179 млн случаев диабета остаются не выявленными [1].Россия находится на 5-м месте в мире по числу боль-ных диабетом после Китая, Индии, США и Бразилии. В нашей стране зарегистрировано почти 11 млн паци-ентов с СД, преимущественно за счет больных СД2 [1]. По данным эпидемиологического исследования, про-веденного в 2011 г., в Москве по обращаемости за 12 лет было зарегистрировано почти 49 тысяч больных СД2, а распространенность данного заболевания составила 1590 человек на 100 тысяч населения [2].Особую проблему составляют хронические ослож-нения СД, такие как диабетическая нейропатия, рети-нопатия, нефропатия, являющиеся основной причиной инвалидизации и смертности больных. Понятие об инкретинахВ последние годы на фармацевтическом рынке появились препараты для лечения СД из класса ин-кретинов. Эндогенные инкретины -это гормоны же-лудочно-кишечного тракта, вырабатывающиеся в ответ на поступление пищи и вызывающие стимуляцию секреции инсулина [3,4]. К ним относятся, прежде всего, глюкагоноподобный пептид-1 (ГПП-1), глюка-гоноподобный пептид-2 (ГПП-2), глюкозозависимый инсулинотропный пептид (ГИП). Все они являются Механизмы нейропротективного действия инкретиномиметиковВласов Т.Д.

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“…at doses of 0.25 (E1 group), 0.5 (E2 group), and 1 μg/kg (E3 group), twice a day for 7 consecutive days. The dosage and duration of treatment with EX-4 was selected according to previous studies that demonstrated the beneficial effect of EX-4 on focal cerebral ischemia-induced infarction in rats (Briyal et al, 2012). One day after the final injection, the mice were sacrificed by cervical dislocation, and the pancreas from each animal was dissected out, weighed, and fixed in 10% formalin.…”

Section: Experimental Designmentioning

confidence: 99%

Exendin-4 effects on islet volume and number in mouse pancreas

Khorsandi

Nejaddehbashi

2013

Braz. J. Pharm. Sci.

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The aim of this study was to evaluate Exendin-4 (EX-4) effects on islet volume and number in the mouse pancreas. Thirty-two healthy adult male NMRI mice were randomly divided into control and experimental groups. EX-4 was injected intraperitoneally (i. p.) at doses of 0.25 (E1 group), 0.5 (E2 group), and 1 μg/kg (E3 group), twice a day for 7 consecutive days. One day after the final injection, the mice were sacrificed, and the pancreas from each animal dissected out, weighed, and fixed in 10% formalin for measurement of pancreas and islet volume, and determination of islet number by stereological assessments. There was a significant increase in the weight of pancreases in the E3 group. Islet and pancreas volumes in E1 and E2 groups were unchanged compared to the control group. The E3 group showed a significant increase in islet and pancreas volume (P < 0.05). There were no significant changes in the total number of islets in all three experimental groups. The results revealed that EX-4 increased pancreas and islet volume in non-diabetic mice. The increased total islet mass is probably caused by islet hypertrophy without the formation of additional islets.Uniterms: Exendin-4/effects/experimental study. Pancreas/effects fo Exendin-4. Islet/hypertrophy. Stereology.O objetivo deste estudo foi avaliar os efeitos do Exendin-4 (EX-4) sobre o volume e número de ilhotas no pâncreas. Trinta e dois camundongos NMRI machos saudáveis e adultos foram divididos ao acaso em grupos controle e grupos experimentais. EX-4 foi injetado intraperitonealmente (i. p.) nas doses de 0,25 (grupo E1), 0,5 (grupo E2) e 1 (grupo E3), duas vezes por dia durante 7 dias consecutivos. Um dia após a injeção final, os camundongos foram sacrificados e o pâncreas de cada animal foi dissecado, pesado e fixado em solução de formaldeído 10% para avaliação do volume do pâncreas e ilhotas e do número de ilhotas por métodos estereológicos. Observou-se aumento significativo no peso de pâncreas no grupo E3. O volume do pâncreas assim como das ilhotas não apresentou alterações nos grupos E1 e E2, quando comparados ao grupo controle No grupo E3 houve aumento significativo no volume do pâncreas e das ilhotas (P<0,05). Não se observaram alterações significativas no número de ilhotas nos três grupos experimentais. Os resultados revelaram que o EX-4 provoca aumento no volume do pâncreas, bem como no volume das ilhotas em camundongos não-diabéticos. O aumento no volume total de ilhotas deve-se, provavelmente, a hipertrofia das ilhotas sem a formação de ilhotas adicionais.Unitermos: Exendina-4/efeitos/estudo experimental. Pâncreas/efeito do Exendina-4. Ilhotas/hipertrofia. Estereologia.

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Repeated administration of exendin-4 reduces focal cerebral ischemia-induced infarction in rats

Cited by 62 publications

References 69 publications

Potentials of incretin‐based therapies in dementia and stroke in type 2 diabetes mellitus

Potentials of incretin‐based therapies in dementia and stroke in type 2 diabetes mellitus

Mechanisms of neuroprotective action of incretin mimetics

Exendin-4 effects on islet volume and number in mouse pancreas

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