Endogenous somatostatin-28 modulates postprandial insulin secretion. Immunoneutralization studies in baboons

Area of Science:

• Endocrinology
• Gastroenterology
• Metabolism

Background:

• Somatostatin-28 (S-28) and somatostatin-14 (S-14) are peptide hormones that inhibit peripheral cellular functions.
• S-28 is secreted by enterocytes post-meal, while S-14 is mainly from gastric and pancreatic D cells.
• The role of S-28 in regulating pancreatic B cell function during nutrient absorption is not fully understood.

Purpose of the Study:

• To investigate the role of S-28 as a humoral regulator of pancreatic B cell function during nutrient absorption.
• To determine if S-28 acts as a incretin within the enteroinsular axis.

Main Methods:

• Baboons were administered a somatostatin-specific monoclonal antibody (mAb) to block S-28 activity.
• Glucose, insulin, glucagon-like peptide-1, growth hormone (GH), and glucagon levels were measured before and after intragastric nutrient administration.
• Insulin and glucose kinetics were assessed to evaluate insulin sensitivity.

Main Results:

• Portal and peripheral S-28 levels increased significantly after meals in baboons.
• Immunoneutralization of S-28 led to elevated postprandial insulin levels on days 1 and 2 post-mAb administration.
• GH levels increased, glucagon levels decreased, and insulin resistance was noted on day 2, with fasting insulin levels rising significantly.

Conclusions:

• S-28 plays a role in the enteroinsular axis, acting as a incretin to regulate postprandial insulin secretion.
• Elevated insulin levels after S-28 blockade suggest its inhibitory effect on insulin secretion during nutrient absorption.
• Increased GH action contributes to insulin resistance, prompting compensatory increases in insulin secretion.