Low density of ghrelin cells in the oxyntic mucosa correlated to slow gastric emptying in patients with type 1 diabetes

Ghrelin is a peptide hormone that has been isolated from the stomach and localized to endocrine cells in the oxyntic mucosa. Ghrelin acts synergistically with GH-releasing hormone and increases appetite and feeding. It also accelerates gastric and small intestinal motility in rodents. Patients with diabetes suffer from slow gastric emptying, giving rise to nausea and vomiting. The present study was undertaken to establish the possible role of ghrelin in slow gastric emptying observed in patients with longstanding type 1 diabetes, and to correlate the results with the metabolic status of these patients. Eleven patients with type 1 diabetes along with 10 and 15 healthy volunteers as controls underwent gastrointestinal endoscopy/biopsy or gastric scintigraphy. Gastric emptying in patients and controls was measured by scintigraphy. Sections from biopsies of the oxyntic mucosa and duodenum were immunostained for ghrelin with the avidin-biotin complex method. The density of the cells was quantified with computerized image analysis. Both the lag phase and half-emptying time (T50) were higher in patients with diabetes than in healthy volunteers. The T50 was correlated with the blood glucose level. The density of ghrelin-immunoreactive cells in the oxyntic mucosa of patients with diabetes was significantly reduced compared to the healthy controls. Ghrelin cell density was correlated with both the lag phase and T50, as well as with blood glucose level. The present finding of reduced density of ghrelin cells in patients with type 1 diabetes, which was well correlated with gastric emptying, indicates the possible role of ghrelin in the pathophysiology of gastroparesis observed in diabetes.