TY - JOUR
T1 - Interleukin 10 Restores Gastric Emptying, Electrical Activity, and Interstitial Cells of Cajal Networks in Diabetic Mice
AU - Choi, Kyoung Moo
AU - Gibbons, Simon J.
AU - Sha, Lei
AU - Beyder, Arthur
AU - Verhulst, Pieter Jan
AU - Cipriani, Gianluca
AU - Phillips, Jessica E.
AU - Bauer, Anthony J.
AU - Ordog, Tamas
AU - Camp, Jon J.
AU - Ge, Xin
AU - Bharucha, Adil E.
AU - Linden, David R.
AU - Szurszewski, Joseph H.
AU - Kashyap, Purna C.
AU - Farrugia, Gianrico
N1 - Publisher Copyright:
© 2016 The Authors.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - Background & Aims: 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.
AB - Background & Aims: 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.
KW - Alternatively Activated Macrophages
KW - Electrical slow wave
KW - Heme oxygenase 1
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U2 - 10.1016/j.jcmgh.2016.04.006
DO - 10.1016/j.jcmgh.2016.04.006
M3 - Article
AN - SCOPUS:84975316787
SN - 2352-345X
VL - 2
SP - 454
EP - 467
JO - CMGH
JF - CMGH
IS - 4
ER -