Endogenously released GIP reduces and GLP-1 increases hepatic insulin extraction

Area of Science:

• Metabolic research
• Endocrinology
• Nutritional science

Background:

• Glucose-dependent insulinotropic peptide (GIP) is implicated in non-alcoholic fatty liver disease (NAFLD) development.
• Isomaltulose, a sucrose alternative, may mitigate NAFLD by influencing GIP levels.
• Understanding the differential effects of isomaltulose and sucrose on incretin hormones is crucial for metabolic health.

Purpose of the Study:

• To compare the effects of isomaltulose versus sucrose on GIP and glucagon-like peptide-1 (GLP-1) secretion.
• To assess the impact on hepatic insulin clearance (HIC) and insulin sensitivity across different glucose tolerance statuses.
• To investigate the relationship between incretin hormones, HIC, and insulin sensitivity.

Main Methods:

• A randomized crossover study involving participants with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM).
• Administration of isomaltulose and sucrose loads, followed by measurements of glucose, insulin, GIP, and GLP-1 levels.
• Calculation of incremental area under the curve (iAUC) for hormones and assessment of insulin sensitivity and HIC.

Main Results:

• Isomaltulose significantly reduced peak glucose and insulin concentrations compared to sucrose across all participant groups.
• Postprandial GIP secretion was decreased, while GLP-1 secretion was significantly increased after isomaltulose intake.
• Isomaltulose intake led to improved insulin sensitivity (35-50%) and enhanced hepatic insulin clearance (HIC), correlated with incretin hormone profiles.

Conclusions:

• Isomaltulose favorably modulates GIP and GLP-1 secretion, leading to improved insulin sensitivity and HIC compared to sucrose.
• GIP levels correlated inversely with HIC, while GLP-1 levels correlated positively, suggesting distinct roles in insulin metabolism.
• Dietary strategies influencing GIP and GLP-1, such as isomaltulose consumption, may be beneficial in managing metabolic dysfunction and insulin resistance.