Role of Mfge8 in the reduced contractility of diabetic gastroparesis

收缩性 内科学 内分泌学 医学 胃轻瘫 糖尿病 胃排空
作者
Dustin Dutcher,Brian A. Perrino
出处
期刊:Physiology [American Physiological Society]
卷期号:38 (S1)
标识
DOI:10.1152/physiol.2023.38.s1.5728770
摘要

Coordinated gastric contractility is imperative for ideal digestion and absorption of nutrients. This is impaired during diabetic gastroparesis, a disorder characterized by abnormal gastric smooth muscle contractions leading to delayed gastric emptying. The objective of this research was to further the understanding of the gastric smooth muscle contraction regulatory mechanisms and how these cascades are affected by diabetes. In addition to its anti-inflammatory properties, it has been shown that milk fat globule-epidermal growth factor 8 (Mfge8) binding to ɑ8β1 integrin decreases murine gastric contractile activity by reducing the inhibitory phosphorylation of MLCP, resulting in MLCP activation and reduced myosin phosphorylation. Additionally, Mfge8 is elevated in human serum from type 2 diabetic individuals compared to non-diabetic individuals. It is hypothesized that elevated levels of Mfge8 in smooth muscle tissue will lead to decreased contractility strength, a phenomenon that would resemble gastroparesis secondary to diabetes. We analyzed the contractility and Mfge8 expression of human gastric antrum smooth muscles from obese diabetic and obese non-diabetic individuals who elected to undergo sleeve gastrectomy surgery for weight loss. Short strips of gastric muscle were stimulated to contract with serial concentrations of carbachol and contractile activity was measured with AcqKnowledge software. Mfge8 protein expression was then analyzed using a Wes Simple western instrument. We report that human gastric antrum smooth muscle tissue levels of Mfge8 are elevated in diabetic obese individuals (n=22) compared to non-diabetic obese individuals (n=37, P=0.004). However, we show that the contractile activity of antrum smooth muscle from diabetic obese individuals (n=38) is not dependent on Mfge8 levels and is not significantly different from the contractility of non-diabetic obese individuals (n=38). The rate of contraction, rate of relaxation, and overall tension ( P=0.40) produced by the muscle tissues from the two groups did not significantly differ from each other. It is possible that Mfge8 was not elevated enough to cause reduced contractility, or that those with elevated Mfge8 had not yet developed symptoms of gastroparesis. Mfge8 may serve as a biomarker for diabetic gastroparesis in the future, and additional research is required to determine the pathologic significance of elevated Mfge8 levels in obese diabetic human gastric antrum smooth muscle. This research was supported by a National Institute of Diabetes and Digestive and Kidney Diseases Diabetic Complications Consortium (DiaComp, http://www.diacomp.org ) Grant DK076169, a Takeda Pharmaceuticals Innovation Center Grant to BP, and a UNRSOM Office of Medical Research Grant FD110-PG08935 to DD. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

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
楠LEE发布了新的文献求助10
刚刚
1秒前
卓涵柏完成签到,获得积分10
1秒前
ZZC10完成签到,获得积分10
2秒前
Hello应助Suyi采纳,获得10
2秒前
宓广缘完成签到 ,获得积分10
3秒前
卓熊关注了科研通微信公众号
4秒前
老迟到的冬萱完成签到,获得积分10
4秒前
星辰大海应助阳光蛋挞采纳,获得10
4秒前
4秒前
墨菲特发布了新的文献求助10
4秒前
丽丽完成签到,获得积分10
6秒前
端庄的煎蛋完成签到,获得积分0
6秒前
6秒前
Lucas应助拉长的人雄采纳,获得10
8秒前
9秒前
10秒前
10秒前
庄冬丽完成签到,获得积分10
10秒前
一一发布了新的文献求助10
10秒前
Hello应助肉肉抱大腿采纳,获得10
11秒前
11秒前
12秒前
务实筝完成签到,获得积分10
13秒前
MM完成签到,获得积分10
13秒前
研友_8Y26PL发布了新的文献求助10
13秒前
Suyi发布了新的文献求助10
13秒前
M27完成签到,获得积分20
13秒前
Owen应助墨菲特采纳,获得10
14秒前
14秒前
hy完成签到,获得积分10
15秒前
16秒前
水上书发布了新的文献求助10
16秒前
zhangwei完成签到,获得积分10
17秒前
在水一方应助顺心火龙果采纳,获得10
17秒前
18秒前
wwww发布了新的文献求助10
18秒前
18秒前
yj1506837246发布了新的文献求助10
18秒前
欢呼的汉堡完成签到,获得积分10
19秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
Toward a Combinatorial Approach for the Prediction of IgG Half-Life and Clearance 500
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 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 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3970004
求助须知:如何正确求助?哪些是违规求助? 3514701
关于积分的说明 11175468
捐赠科研通 3250051
什么是DOI,文献DOI怎么找? 1795187
邀请新用户注册赠送积分活动 875630
科研通“疑难数据库(出版商)”最低求助积分说明 804925