Investigating Intestinal Glucagon After Roux-en-Y Gastric Bypass Surgery

Area of Science:

• Endocrinology and Metabolism
• Gastroenterology
• Bariatric Surgery Research

Background:

• Roux-en-Y gastric bypass (RYGB) surgery is associated with increased postprandial plasma glucagon concentrations.
• This occurs despite improved glucose tolerance and elevated levels of insulin and glucagon-like peptide 1 (GLP-1) post-RYGB.
• The origin of RYGB-induced hyperglucagonemia remains unclear.

Purpose of the Study:

• To investigate the potential gut origin of increased glucagon levels following RYGB surgery.
• To determine if the small intestine contributes to hyperglucagonemia after RYGB.

Main Methods:

• A substudy involving 8 morbidly obese individuals (with or without type 2 diabetes) undergoing RYGB.
• Gastrointestinal mucosal biopsy specimens were collected via upper enteroscopy before and 3 months after RYGB.
• Plasma and tissue glucagon concentrations were measured using mass spectrometry-validated immunoassays and immunohistochemistry.

Main Results:

• Postprandial plasma glucagon concentrations were significantly increased after RYGB.
• Glucagon gene expression in the small intestine increased, and glucagon was detected in small-intestine biopsy specimens post-RYGB.
• Immunohistochemistry revealed cells in the small intestine co-stained for GLP-1 and glucagon after RYGB.

Conclusions:

• Increased glucagon concentrations are found in both small-intestine biopsy specimens and postprandial plasma after RYGB.
• The presence of glucagon-producing cells in the small intestine suggests a gut-derived source.
• Enteroendocrine L cells in the small intestine likely contribute to postprandial hyperglucagonemia following RYGB.