Vildagliptin inhibits high fat and fetuin-A mediated DPP-4 expression, intracellular lipid accumulation and improves insulin secretory defects in pancreatic beta cells

内科学 内分泌学 维尔达格利普汀 肠促胰岛素 小岛 胰岛素 化学 胰岛素抵抗 二肽基肽酶-4 炎症 促炎细胞因子 糖尿病 生物 医学 2型糖尿病
作者
Snehasish Nag,Samanwita Mandal,Oindrila Mukherjee,Tanmay Majumdar,Satinath Mukhopadhyay,Rakesh Kundu
出处
期刊:Biochimica Et Biophysica Acta: Molecular Basis Of Disease [Elsevier]
卷期号:1870 (3): 167047-167047 被引量:3
标识
DOI:10.1016/j.bbadis.2024.167047
摘要

Dipeptidyl peptidase-4 (DPP-4), a ubiquitous proteolytic enzyme, inhibits insulin secretion from pancreatic beta cells by inactivating circulating incretin hormones GLP-1 and GIP. High circulating levels of DPP-4 is presumed to compromise insulin secretion in people with type 2 diabetes (T2D). Our group recently reported lipid induced DPP-4 expression in pancreatic beta cells, mediated by the TLR4-NF-kB pathway. In the present study, we looked at the role of Vildagliptin on pancreatic DPP-4 inhibition, preservation of islet mass and restoration of insulin secretion. MIN6 mouse insulinoma cells incubated with palmitate and fetuin-A, a proinflammatory organokine associated with insulin resistance, showed activation of TLR4-NF-kB pathway, which was rescued upon Vildagliptin treatment. In addition, Vildagliptin, by suppressing palmitate-fetuin-A mediated DPP-4 expression in MIN6, prevented the secretion of IL-1beta and fetuin-A level in the culture media. DPP-4 siRNA abrogated TLR4-NFkB pathway mediated islet cell inflammation. Vildagliptin also reduced palmitate-fetuin-A mediated intracellular lipid accumulation in MIN6 and isolated islets from high fat fed (HFD) mice as observed by Oil O Red staining with downregulation of CD36 and PPARgamma. Vildagliptin also preserved islet mass and rescued insulin secretory defect in HFD mice. Our results suggest that inhibition of DPP-4 by Vildagliptin protects pancreatic beta cells from the deleterious effects of lipid and fetuin-A, preserves insulin secretory functions and improves hyperglycemia.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
1秒前
科研小狗发布了新的文献求助10
2秒前
4秒前
李爱国应助CC采纳,获得10
4秒前
Jasper应助lvsehx采纳,获得10
4秒前
5秒前
5秒前
6秒前
8秒前
8秒前
xhtt完成签到,获得积分10
8秒前
鲍文启发布了新的文献求助10
10秒前
外向谷菱发布了新的文献求助10
10秒前
木禾发布了新的文献求助10
10秒前
烟花应助HonestLiang采纳,获得10
10秒前
zdesfsfa完成签到,获得积分10
10秒前
伯赏元彤发布了新的文献求助10
11秒前
昂口3完成签到 ,获得积分10
12秒前
RONG应助liuzhou采纳,获得10
12秒前
12秒前
14秒前
王蒙发布了新的文献求助10
14秒前
14秒前
14秒前
15秒前
15秒前
wfy1227完成签到,获得积分10
15秒前
18秒前
CC发布了新的文献求助10
18秒前
19秒前
伯赏元彤完成签到,获得积分10
19秒前
20秒前
22秒前
大模型应助阿元采纳,获得10
24秒前
Ava应助科研通管家采纳,获得10
24秒前
行走的sci发布了新的文献求助10
24秒前
CodeCraft应助科研通管家采纳,获得10
24秒前
烟花应助科研通管家采纳,获得10
24秒前
酷波er应助科研通管家采纳,获得10
24秒前
大模型应助科研通管家采纳,获得10
24秒前
高分求助中
Licensing Deals in Pharmaceuticals 2019-2024 3000
Very-high-order BVD Schemes Using β-variable THINC Method 1020
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 800
錢鍾書楊絳親友書札 600
A new species of Coccus (Homoptera: Coccoidea) from Malawi 500
Geochemistry, 2nd Edition 地球化学经典教科书第二版,不要epub版本 431
Mission to Mao: Us Intelligence and the Chinese Communists in World War II 400
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3293068
求助须知:如何正确求助?哪些是违规求助? 2929268
关于积分的说明 8440967
捐赠科研通 2601379
什么是DOI,文献DOI怎么找? 1419826
科研通“疑难数据库(出版商)”最低求助积分说明 660411
邀请新用户注册赠送积分活动 643045