title: Macrophages in diabetic gastroparesis--the missing link?
abstract: BACKGROUND
  Diabetic gastroparesis results in significant morbidity for patients and major economic burden for society. Treatment options for diabetic gastroparesis are currently directed at symptom control rather than the underlying disease and are limited. The pathophysiology of diabetic gastroparesis includes damage to intrinsic and extrinsic neurons, smooth muscle, and interstitial cells of Cajal (ICC). Oxidative damage in diabetes appears to be one of the primary insults involved in the pathogenesis of several complications of diabetes, including gastroparesis. Recent studies have highlighted the potential role of macrophages as key cellular elements in the pathogenesis of diabetic gastroparesis. Macrophages are important for both homeostasis and defense against a variety of pathogens. Heme oxygenase 1 (HO1), an enzyme expressed in a subset of macrophages has emerged as a major protective mechanism against oxidative stress. Activation of macrophages with high levels of HO1 expression protects against development of delayed gastric emptying in animal models of diabetes, while activation of macrophages that do not express HO1 are linked to neuromuscular cell injury. Targeting macrophages and HO1 may therefore be a therapeutic option in diabetic gastroparesis.
  
  
  OBJECTIVE
  This report briefly reviews the pathophysiology of diabetic gastroparesis with a focus on oxidative damage and how activation and polarization of different subtypes of macrophages in the muscularis propria determines development of delay in gastric emptying or protects against its development.
authors.affiliation: Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, MN, USA.
authors.forename: L
authors.initials: L
authors.lastname: Neshatian
authors.forename: S J
authors.initials: SJ
authors.lastname: Gibbons
authors.forename: G
authors.initials: G
authors.lastname: Farrugia
mesh_terms: D000818:Animals; D048909:Diabetes Complications / Q000201:enzymology / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000503:physiopathology; D041981:Gastrointestinal Tract; D018589:Gastroparesis / Q000150:complications* / Q000201:enzymology / Q000503:physiopathology*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006801:Humans; D056885:Interstitial Cells of Cajal / Q000502:physiology; D008264:Macrophages / Q000201:enzymology / Q000502:physiology*; D051379:Mice; D018384:Oxidative Stress; D051381:Rats
chemical_list: D006419:Heme Oxygenase (Decyclizing)
keywords: diabetic gastroparesis; heme oxygenase 1; macrophage; macrophage polarization; oxidative stress