Cellular pathogenesis of diabetic gastroenteropathy.
Gastroenteropathy manifesting in upper gastrointestinal symptoms, delayed gastric emptying, constipation, diarrhea and fecal incontinence occurs frequently in patients with diabetes mellitus and represents a significant health care burden. Current treatments are largely symptomatic and ineffective. Better understanding of the cellular and molecular pathogenesis of these disorders is required for the development of more effective therapies. Recent advances in our understanding of the inherent, high-level complexities of the control systems that execute and regulate gastrointestinal motility, together with the utilization of new experimental models and sophisticated physiological, morphological and molecular techniques have lead to the realization that diabetic gastroenteropathies cannot be ascribed to any singular defect or dysfunction. In fact, these disorders are multifactorial and involve a spectrum of metabolic and dystrophic changes that can potentially affect all key components of motor control including the systemic autonomic and enteric nervous systems, interstitial cells of Cajal and smooth muscle cells. Candidate pathomechanisms are also varied and include imbalance between pro- and anti-oxidative factors, altered trophic stimuli to mature cells and their progenitors, and, possibly, autoimmune factors. The goal of this paper is to review the cellular changes underlying diabetic gastroenteropathies and their potential causes, with particular focus on functional interactions between various cell types. It is proposed that diabetic gastroenteropathies should be considered a form of gastrointestinal neuromuscular dystrophy rather than a "functional" disorder. Future research should identify ways to block cytotoxic factors, support the regeneration of damaged cells and translate the experimental findings into new treatment modalities.
Ordög
T
T
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA. ordog.tamas@mayo.edu
Hayashi
Y
Y
Gibbons
S J
SJ
D000818:Animals; D048909:Diabetes Complications / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D005767:Gastrointestinal Diseases / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D005769:Gastrointestinal Motility; D006801:Humans