title: Blockade of Central GLP-1 Receptors Deteriorates the Improvement of Diabetes after Ileal Transposition.
abstract: Background:The mechanism of improvement of type 2 diabetes mellitus induced by ileal transposition (IT) is undefined. Our aim was to investigate the possible role of central glucagon-like peptide 1 (GLP-1) after IT.Methods:Ninety male diabetic rats were randomly divided into the IT, sham IT (S-IT) and control group. The food intake, glucose metabolism and GLP-1 level were measured. Subsequently, we administered GLP-1 antagonist via lateral brain ventricle cannula to block central GLP-1 receptor, and verified whether the food intake, glucose metabolism changed. And the activated pro-opiomelanocortin (POMC) neurons in different groups were compared after sacrifice.Results:IT induced significant diabetic improvement with decreased maximum food intake and higher postprandial GLP-1 level. The GLP-1 level in cerebrospinal fluid increased in correlation with the plasma GLP-1 level. When the central GLP-1 receptor antagonist was given to the IT group rats, the improvement of the glucose level declined. The glucose level surged (169.9 ± 14.2) % during the oral glucose tolerance test, the range was larger than that before central blockade ((67.1 ± 14.2) %,P< 0.001). Moreover, the POMC neuron number in the arcuate nucleus of the hypothalamus were reduced (12.7 ± 6.1 at a magnification of 100×). The relative content level of POMC-derived peptides in the pituitary was lower (0.1 ± 0.05).Conclusions:The central GLP-1 might play an important role in the remission of diabetes after IT. POMC neurons in the hypothalamus may be activated by the enhanced level of GLP-1 after IT.
authors.affiliation: Department of Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1#, Beijing 100730, P. R. China.
authors.forename: Weijie
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1#, Beijing 100730, P. R. China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1#, Beijing 100730, P. R. China.
authors.forename: Yiding
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1#, Beijing 100730, P. R. China.
authors.forename: Jiaolin
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Clinical Laboratory of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1#, Beijing 100730, P. R. China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1#, Beijing 100730, P. R. China.
authors.forename: Guole
authors.initials: G
authors.lastname: Lin
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of the Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1#, Beijing 100730, P. R. China.
authors.forename: Fengying
authors.initials: F
authors.lastname: Gong
mesh_terms: D000818:Animals; D050110:Bariatric Surgery / Q000379:methods*; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism / Q000601:surgery*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism / Q000601:surgery; D004435:Eating / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism*; D007082:Ileum / Q000601:surgery; D008297:Male; D011897:Random Allocation; D051381:Rats
chemical_list: D001786:Blood Glucose; D000067757:Glucagon-Like Peptide-1 Receptor; D052216:Glucagon-Like Peptide 1
keywords: bariatric surgery; glucagon-like peptide-1; ileal transposition; neuron.; type 2 diabetes mellitus