Older Subjects With β-Cell Dysfunction Have an Accentuated Incretin Release

Area of Science:

• Endocrinology
• Metabolism
• Gerontology

Background:

• Insulin secretion (IS) declines with age, increasing risk for impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM).
• Incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), regulate IS.
• Age-related decline in incretin release and its association with beta-cell dysfunction are not fully understood.

Purpose of the Study:

• To test if incretin hormone release is lower in older adults.
• To determine if reduced incretin release is linked to beta-cell dysfunction.
• To investigate the role of GLP-1 and GIP in age-related glucose intolerance.

Main Methods:

• Oral glucose tolerance test (OGTT) in young (n=40) and older (n=53) non-diabetic subjects.
• Categorization into young normal glucose tolerance (Y-NGT), older normal glucose tolerance (O-NGT), and older impaired glucose tolerance (O-IGT) groups.
• Measurement of plasma insulin, C-peptide, GLP-1, and GIP; calculation of insulin sensitivity (Matsuda index) and insulin secretory rate (ISR).

Main Results:

• Older adults with IGT (O-IGT) showed lower insulin sensitivity and early-phase ISR compared to young adults (Y-NGT).
• GLP-1 concentrations were elevated in both older groups (O-NGT and O-IGT) compared to Y-NGT.
• GIP secretion was higher in O-NGT subjects than in Y-NGT subjects, but not significantly different in O-IGT.

Conclusions:

• Aging is associated with an exaggerated GLP-1 secretory response.
• This enhanced GLP-1 response in older adults is insufficient to improve first-phase insulin release in individuals with IGT.
• The exaggerated GLP-1 response does not overcome insulin resistance, highlighting a potential mechanism for T2DM development in aging populations.