Abnormal Ghrelin and Pancreatic Polypeptide Responses in Gastroparesis

Abstract

Vagal nerve dysfunction has been implicated in the pathogenesis of diabetic gastroparesis, but its role in idiopathic gastroparesis remains uncertain. The increase in pancreatic polypeptide with sham feeding is often used as a measure of vagal integrity. Ghrelin has been suggested to function as an appetite-stimulating hormone from the gut to the brain acting through vagal afferent pathways. Systemic ghrelin also rises in part due to vagal efferent pathways. Alterations in ghrelin and its effects on appetite could play a role in gastroparesis. In this study we aimed [1] to investigate the presence of vagal nerve dysfunction in patients with idiopathic and diabetic gastroparesis and [2] to determine if alterations in ghrelin concentrations occur in gastroparesis. Normal subjects and patients with diabetic, idiopathic, or postsurgical gastroparesis underwent a sham feeding protocol. Serial blood samples were obtained for plasma ghrelin and pancreatic polypeptide. Sham feeding was characterized by an increase in pancreatic polypeptide and ghrelin in normal controls and patients with idiopathic gastroparesis. The changes in pancreatic polypeptide and ghrelin levels in diabetic and postsurgical gastroparesis were significantly less than those in normal subjects. Vagal nerve dysfunction, as evidenced by an impaired pancreatic polypeptide response with sham feeding, is present in diabetic gastroparesis but not idiopathic gastroparesis. Systemic ghrelin concentrations increased with sham feeding in normal subjects and patients with idiopathic gastroparesis but not in diabetic or postsurgical gastroparesis. Vagal function and regulation of ghrelin levels are impaired in diabetic gastroparesis.

Ghrelin and Obestatin Levels in Type 2 Diabetic Patients With and Without Delayed Gastric Emptying

“…These findings are in accordance with a study of Gaddipati et al [14]. Those authors studied the ghrelin and pancreatic polypeptide responses in healthy subjects and patients with diabetic, idiopathic, or postsurgical gastroparesis after sham feeding as a measure of vagal integrity.…”

Vagal Nerve Regulation Is Essential for the Increase in Gastric Motility in Response to Mild Exercise

“…Ghrelin stimulates short-term food intake, promotes gastric emptying, and regulates body weight. In patients with anorexia or post-bariatric surgery, profound changes in plasma ghrelin levels were found, suggesting that it is an important hormone in the regulation of body weight (Gaddipati et al 2006;Jürimäe et al 2007). Studies on the effects of acute or chronic exercise showed that high-intensity exercise could lower plasma ghrelin levels in rats (Ghanbari-Niaki et al 2008;Wang et al 2008;GhanbariNiaki et al 2009).…”

No Ghrelin Response to Oral Glucose in Diabetes Mellitus with Gastroparesis

“…Thus, suppression of ghrelin by food or an oral glucose load may not be regulated by the plasma level of glucose and/or insulin, but rather by some direct or indirect information from the gastrointestinal tract. Very recently, Gaddipati et al reported that sham feeding could increase the plasma ghrelin level in normal subjects, while such a response of ghrelin was not observed in patients with diabetic gastroparesis [27]. In contrast, Arosio et al reported that circulating ghrelin concentrations decreased with sham feeding as they do with actual meal ingestion in humans [28].…”