title: Interleukin 10 Restores Gastric Emptying, Electrical Activity, and Interstitial Cells of Cajal Networks in Diabetic Mice.
abstract: OBJECTIVE
  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.
authors: Enteric NeuroScience Program, Mayo Clinic School of Medicine, Rochester, Minnesota.
authors: Kyoung Moo
authors: KM
authors: Choi
authors: Enteric NeuroScience Program, Mayo Clinic School of Medicine, Rochester, Minnesota.
authors: Simon J
authors: SJ
authors: Gibbons
authors: Enteric NeuroScience Program, Mayo Clinic School of Medicine, Rochester, Minnesota.
authors: Lei
authors: L
authors: Sha
authors: Enteric NeuroScience Program, Mayo Clinic School of Medicine, Rochester, Minnesota.
authors: Arthur
authors: A
authors: Beyder
authors: Enteric NeuroScience Program, Mayo Clinic School of Medicine, Rochester, Minnesota.
authors: Pieter-Jan
authors: PJ
authors: Verhulst
authors: Enteric NeuroScience Program, Mayo Clinic School of Medicine, Rochester, Minnesota.
authors: Gianluca
authors: G
authors: Cipriani
authors: Enteric NeuroScience Program, Mayo Clinic School of Medicine, Rochester, Minnesota.
authors: Jessica E
authors: JE
authors: Phillips
authors: Department of Integrative Physiology and Pharmacology, Liberty University College of Osteopathic Medicine, Lynchburg, Virginia.
authors: Anthony J
authors: AJ
authors: Bauer
authors: Enteric NeuroScience Program, Mayo Clinic School of Medicine, Rochester, Minnesota.
authors: Tamas
authors: T
authors: Ordog
authors: Enteric NeuroScience Program, Mayo Clinic School of Medicine, Rochester, Minnesota.
authors: Jon J
authors: JJ
authors: Camp
authors: Enteric NeuroScience Program, Mayo Clinic School of Medicine, Rochester, Minnesota.
authors: Xin
authors: X
authors: Ge
authors: Enteric NeuroScience Program, Mayo Clinic School of Medicine, Rochester, Minnesota.
authors: Adil E
authors: AE
authors: Bharucha
authors: Enteric NeuroScience Program, Mayo Clinic School of Medicine, Rochester, Minnesota.
authors: David R
authors: DR
authors: Linden
authors: Enteric NeuroScience Program, Mayo Clinic School of Medicine, Rochester, Minnesota.
authors: Joseph H
authors: JH
authors: Szurszewski
authors: Enteric NeuroScience Program, Mayo Clinic School of Medicine, Rochester, Minnesota.
authors: Purna C
authors: PC
authors: Kashyap
authors: Enteric NeuroScience Program, Mayo Clinic School of Medicine, Rochester, Minnesota.
authors: Gianrico
authors: G
authors: Farrugia
keywords: Alternatively Activated Macrophages; CO, carbon monoxide; Electrical Slow Wave; HO1, heme oxygenase 1; Heme Oxygenase 1; ICC, interstitial cells of Cajal; IL10, interleukin 10; MDA, malondialdehyde; NADPH, reduced nicotinamide adenine dinucleotide phosphate; NOD, nonobese diabetic; NOS, nitric oxide synthase; PBS, phosphate-buffered saline