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Int J Med Sci 2016; 13(12):955-962. doi:10.7150/ijms.17290

Research Paper

Blockade of Central GLP-1 Receptors Deteriorates the Improvement of Diabetes after Ileal Transposition

Weijie Chen1, Qianqian Xu1, Yiding Xiao1, Jiaolin Zhou1, Weimin Zhang2, Guole Lin1✉, Fengying Gong3

1. Department of Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1#, Beijing 100730, P. R. China.
2. Clinical Laboratory of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1#, Beijing 100730, P. R. China.
3. 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.

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.

Keywords: type 2 diabetes mellitus, bariatric surgery, ileal transposition, glucagon-like peptide-1, neuron.

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How to cite this article:
Chen W, Xu Q, Xiao Y, Zhou J, Zhang W, Lin G, Gong F. Blockade of Central GLP-1 Receptors Deteriorates the Improvement of Diabetes after Ileal Transposition. Int J Med Sci 2016; 13(12):955-962. doi:10.7150/ijms.17290. Available from http://www.medsci.org/v13p0955.htm