Alterations in pancreatic islet cell function in response to small bowel resection

Area of Science:

• Endocrinology
• Gastroenterology
• Metabolic Surgery

Background:

• Intestinal resection significantly impacts metabolic homeostasis.
• The specific effects of small bowel resection on pancreatic islet function and gut hormone regulation remain largely unknown.
• Glucagon-like peptide-1 (GLP-1) signaling is recognized for its role in glucose regulation and insulin sensitivity.

Purpose of the Study:

• To investigate the consequences of 50% small bowel resection (SBR) on pancreatic β-cell morphology, proliferation, and glucagon-like peptide-1 (GLP-1) expression in mice.
• To elucidate the role of GLP-1 in the enteropancreatic axis following SBR.
• To assess the therapeutic potential of GLP-1 agonist administration in mitigating SBR-induced metabolic disturbances.

Main Methods:

• Surgical 50% proximal small bowel resection (SBR) or sham operation in C57BL/6 mice.
• Assessment of pancreatic insulin content and secretion (ELISA, static incubation, islet perfusion).
• Immunohistochemistry for α- and β-cell structure, Western blot for GLP-1 receptor (GLP-1R) expression, and immunoassay for plasma insulin and GLP-1 levels.

Main Results:

• SBR led to pancreatic islet hypertrophy and impaired glucose tolerance, without altering α- and β-cell proportions.
• Insulin secretion was significantly reduced in SBR mice, indicating a perturbed second phase of insulin release.
• Expression of pancreatic GLP-1R and serum GLP-1 levels were decreased by approximately twofold in SBR mice compared to controls.

Conclusions:

• Massive small bowel resection causes significant pancreatic islet hypertrophy and impaired insulin secretion, mediated by reduced GLP-1 signaling.
• Decreased GLP-1 and GLP-1R expression following SBR presents a novel mechanism in enteropancreatic glucose regulation.
• Administration of a GLP-1 agonist effectively mitigated the metabolic derangements observed after SBR, highlighting its therapeutic potential.