Sodium-glucose co-transporter 1 (SGLT1) differentially regulates gluconeogenesis and GLP-1 receptor (GLP-1R) expression in different diabetic rats: a preliminary validation of the hypothesis of SGLT1 bridge as an indication for surgical diabetes

doi:10.21037/atm-22-1769

科研成果详情

题名	Sodium-glucose co-transporter 1 (SGLT1) differentially regulates gluconeogenesis and GLP-1 receptor (GLP-1R) expression in different diabetic rats: a preliminary validation of the hypothesis of SGLT1 bridge as an indication for surgical diabetes
作者	Zhu, Hengliang 1,2,3,4; Cai, Huajie5; Wang, Xiaokun 6; Chen, Tao 1,2; Zhen, Chaohui 3,4; Zhang, Zhenzhan 1,2; Ruan, Xiaojiao5; Li, Guoxin 1,2
发表日期	2022-04
发表期刊	ANNALS OF TRANSLATIONAL MEDICINE 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	Sodium-glucose co-transporter 1 (SGLT1) diabetes glucagon-like peptide-1 (GLP-1) gluconeogenesis (GNG) metabolic surgery
其他关键词	GLUCAGON-LIKE PEPTIDE-1 ; DUODENAL-JEJUNAL BYPASS ; Y GASTRIC BYPASS ; SMALL-INTESTINE ; SLEEVE GASTRECTOMY ; TRANSPORTER SGLT1 ; METABOLIC-CHANGES ; SALIVARY-GLANDS ; MOUSE MODELS ; FOOD-INTAKE
摘要	Background: Sodium-glucose co-transporter 1 (SGLT1) may play a synergistic role in gluconeogenesis (GNG) and glucagon-like peptide-1 (GLP-1) expression. We proposed the hypothesis of a SGLT1 bridge as an indication for surgical diabetes that was preliminary validated in the present study. Methods: We selected nonobese diabetic Goto-Kakizaki (GK) rats and Zuker diabetic fat (ZDF) rats to represent advanced and early diabetes, respectively. Based on glucose gavage with or without SGLT1 inhibitor phlorizin, the rats were divided into 4 groups: Gk-Glu, GK-P, ZDF-Glu, and ZDF-P. The expressions of SGLT1, GLP-1 receptor (GLP-1R), glucose-6 phosphatase (G6Pase), and phosphoenolpyruvate carboxykinase-1 (Pck1) were determined by immunohistochemistry (IHC) or quantitative reverse transcription polymerase chain reaction (RT-qPCR), and the effects of phlorizin were analyzed. Results: Glucose tolerance was worse in GK rats and the homeostasis model assessment-insulin resistance (HOMA-IR) was higher in ZDF rats, indicating different pathophysiological conditions between the different diabetic rats. GK rats showed higher activity of duodenal SGLT1 (P=0.022) and jejunal SGLT1 mRNA expression (P=0.000) and lower SGLT1 mRNA expression in the liver (P=0.0 00) and pancreas (P=0.000). Phlorizin effectively inhibited the activity of duodenal SGLT1 in both GK rats (P=0.000) and ZDF rats (P=0.000). In ZDF rats, the expression of GLP-1R mRNA was downregulated in the jejunum (P=0.001) and upregulated in the pancreas (P=0.021) by phlorizin, but there were no regulatory effects on GLP-1R mRNA in the jejunum and pancreas of GK rats. As for the regulatory effects on GNG, phlorizin upregulated Pck1 mRNA in the duodenum (P=0.000) and the jejunum (P=0.038), whereas it downregulated hepatic G6Pase mRNA in ZDF rats (P=0.005) and Pck1 mRNA expression in GK rats (P=0.001), suggesting that SGLT1 inhibitor may have upregulated intestinal GNG in ZDF rats and downregulated hepatic GNG in both ZDF and GK rats. Conclusions: SGLT1 showed synergistic regulatory effects on the entero-insular axis (EIA) and the gut-brain-liver axis (GBLA), preliminarily validating the hypothesis of a SGLT1 bridge. The distinct expression of SGLT1 and its differentially regulatory effects on diabetic rats with different pathophysiological conditions may provide probable potential indications involved in the Surgical Diabetes that is supposed as the inclusion for diabetic surgery.
资助项目	Natural Science Foundation of Shenzhen University General Hospital [SUGH2019QD016]; Sanming Project of Medicine in Shenzhen [SZSM202111002]
出版者	AME PUBL CO
出版地	SHATIN
ISSN	2305-5839
EISSN	2305-5847
卷号	10 期号:8 页码:481
DOI	10.21037/atm-22-1769
页数	17
WOS类目	Oncology ; Medicine, Research & Experimental
WOS研究方向	Oncology ; Research & Experimental Medicine
WOS记录号	WOS:000792118500001
收录类别	SCIE ; PUBMED
URL	查看原文
PubMed ID	35571394
通讯作者地址	[Li, Guoxin]Southern Med Univ, Nanfang Hosp, Dept Gen Surg, Guangzhou 510515, Peoples R China. ; [Li, Guoxin]Southern Med Univ, Nanfang Hosp, Guangdong Prov Key Lab Precis Med Gastrointestina, Guangzhou 510515, Peoples R China.
引用统计	被引频次[WOS]：0 [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/148062
专题	附属第一医院_胃肠外科
通讯作者	Li, Guoxin
作者单位	1.Southern Med Univ, Nanfang Hosp, Dept Gen Surg, Guangzhou 510515, Peoples R China; 2.Southern Med Univ, Nanfang Hosp, Guangdong Prov Key Lab Precis Med Gastrointestina, Guangzhou 510515, Peoples R China; 3.Shenzhen Univ, Shenzhen Univ Gen Hosp, Dept Gen Surg, Shenzhen, Peoples R China; 4.Shenzhen Univ, Clin Med Acad, Shenzhen, Peoples R China; 5.Wenzhou Med Univ, Dept Gastrointestinal Surg, Affiliated Hosp 1, Wenzhou, Peoples R China; 6.Ganzhou Peoples Hosp, Dept Gastrointestinal & Hernia Surg, Ganzhou, Peoples R China
推荐引用方式 GB/T 7714	Zhu, Hengliang,Cai, Huajie,Wang, Xiaokun,et al. Sodium-glucose co-transporter 1 (SGLT1) differentially regulates gluconeogenesis and GLP-1 receptor (GLP-1R) expression in different diabetic rats: a preliminary validation of the hypothesis of SGLT1 bridge as an indication for surgical diabetes[J]. ANNALS OF TRANSLATIONAL MEDICINE,2022,10(8):481.
APA	Zhu, Hengliang., Cai, Huajie., Wang, Xiaokun., Chen, Tao., Zhen, Chaohui., ... & Li, Guoxin. (2022). Sodium-glucose co-transporter 1 (SGLT1) differentially regulates gluconeogenesis and GLP-1 receptor (GLP-1R) expression in different diabetic rats: a preliminary validation of the hypothesis of SGLT1 bridge as an indication for surgical diabetes. ANNALS OF TRANSLATIONAL MEDICINE, 10(8), 481.
MLA	Zhu, Hengliang,et al."Sodium-glucose co-transporter 1 (SGLT1) differentially regulates gluconeogenesis and GLP-1 receptor (GLP-1R) expression in different diabetic rats: a preliminary validation of the hypothesis of SGLT1 bridge as an indication for surgical diabetes".ANNALS OF TRANSLATIONAL MEDICINE 10.8(2022):481.