Interleukin 10 Restores Gastric Emptying, Electrical Activity, and Interstitial Cells of Cajal Networks in Diabetic Mice

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• 作者：Kyoung Moo Choi¹ ; ^&lowast ; ; Simon J. Gibbons¹ ; ^&lowast ; ; Lei Sha¹ ; Arthur Beyder¹ ; Pieter-Jan Verhulst¹ ; Gianluca Cipriani¹ ; Jessica E. Phillips¹ ; Anthony J. Bauer² ; Tamas Ordog¹ ; Jon J. Camp¹ ; Xin Ge¹ ; Adil E. Bharucha¹ ; David R. Linden¹ ; Joseph H. Szurszewski¹ ; Purna C. Kashyap¹ ; Gianrico Farrugia¹ ; ^{Farrugia.gianrico@mayo.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Alternatively Activated Macrophages ; Heme Oxygenase 1 ; Electrical Slow Wave
• 刊名：CMGH Cellular and Molecular Gastroenterology and Hepatology
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：2
• 期：4
• 页码：454-467
• 全文大小：4011 K

文摘

Gastroparesis is a complication of diabetes characterized by delayed emptying of stomach contents and accompanied by early satiety, nausea, vomiting, and pain. No safe and reliable treatments are available. Interleukin 10 (IL10) activates the M2 cytoprotective phenotype of macrophages and induces expression of heme oxygenase 1 (HO1) protein. We investigated whether IL10 administration could improve gastric emptying and reverse the associated cellular and electrical abnormalities in diabetic mice.

Methods

Nonobese diabetic mice with delayed gastric emptying were given either IL10 (0.1–1 μg, twice/day) or vehicle (controls). Stomach tissues were isolated, and sharp microelectrode recordings were made of the electrical activity in the gastric muscle layers. Changes to interstitial cells of Cajal (ICC), reduced nicotinamide adenine dinucleotide phosphate diaphorase, and levels and distribution of HO1 protein were determined by histochemical and imaging analyses of the same tissues.

Results

Gastric emptying remained delayed in vehicle-treated diabetic mice but returned to normal in mice given IL10 (n = 10 mice; P < .05). In mice given IL10, normalization of gastric emptying was associated with a membrane potential difference between the proximal and distal stomach, and lower irregularity and higher frequency of slow-wave activity, particularly in the distal stomach. Levels of HO1 protein were higher in stomach tissues from mice given IL10, and ICC networks were more organized, better connected, and more evenly distributed compared with controls.

Conclusions

IL10 increases gastric emptying in diabetic mice and has therapeutic potential for patients with diabetic gastroparesis. This response is associated with up-regulation of HO1 and repair of connectivity of ICC networks.