title: Sleeve gastrectomy activates the GLP-1 pathway in pancreatic β cells and promotes GLP-1-expressing cells differentiation in the intestinal tract.
abstract: Db/db mouse was used to study the underlying mechanisms by which Sleeve gastrectomy (SG) improves β-cell function. We investigated β-cell function, plasma active GLP-1 levels, the GLP-1R pathway in β cells and L cell differentiation. After SG, β-cell function was significantly increased, and the GLP-1R-PKCζ-PDX-1 pathway was active in β cells. Plasma active GLP-1 levels, as well as the number of L cells in the jejunum, were significantly increased after SG. The expression of early transcription factors (TF), including Ngn3, FoxA1 and Nkx2.2, was not compromised by chronic hyperglycemia. In contrast, the expression of the downstream TF PAX6 was affected, and this down-regulation could be reversed by SG. So, SG can maintain L cell differentiation, increase plasma active GLP-1 level, sustain the activation of the GLP-1R pathway and improve β cell function in Db/db mice. Our results show that SG can overall improve the function of the entero-insular axis.
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tong-Ji University, 301 Middle Yan-Chang Road, Shanghai, 200072, China. Electronic address: med193@126.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Diseases and Shanghai Institute of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai, 200025, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tong-Ji University, 301 Middle Yan-Chang Road, Shanghai, 200072, China.
authors.forename: Manna
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tong-Ji University, 301 Middle Yan-Chang Road, Shanghai, 200072, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tong-Ji University, 301 Middle Yan-Chang Road, Shanghai, 200072, China. Electronic address: qushencn@hotmail.com.
authors.forename: Shen
authors.initials: S
authors.lastname: Qu
mesh_terms: D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation; D005743:Gastrectomy; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D005951:Glucose Tolerance Test; D000090322:Homeobox Protein Nkx-2.2; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism*; D007422:Intestines / Q000166:cytology*; D008810:Mice, Inbred C57BL; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D000099221:Protein Kinase C zeta
chemical_list: D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D000090322:Homeobox Protein Nkx-2.2; D011493:Protein Kinase C; D014157:Transcription Factors; D000099221:Protein Kinase C zeta; C000715627:Nkx2-2 protein, mouse
keywords: GLP-1; GLP-1 receptor; L cell differentiation; PAX6; PKCζ; Sleeve gastrectomy