Glucose-dependent insulinotropic polypeptide inhibits bone resorption in humans

Area of Science:

• Endocrinology
• Bone Metabolism
• Human Physiology

Background:

• Gut hormones, particularly glucose-dependent insulinotropic polypeptide (GIP), are implicated in postprandial bone resorption reduction.
• Preclinical studies suggest GIP influences bone metabolism with both antiresorptive and anabolic effects.
• The specific role of GIP in human bone homeostasis remains largely unknown.

Purpose of the Study:

• To investigate the effect of GIP administration on bone resorption in healthy human subjects.
• To determine if GIP influences markers of bone resorption during euglycemic and hyperglycemic conditions.

Main Methods:

• Ten healthy subjects underwent 90-minute glucose clamps under euglycemic and hyperglycemic conditions.
• GIP or placebo was co-infused during the clamps.
• Plasma concentrations of C-terminal telopeptide of type I collagen (CTX), a bone resorption marker, were measured.

Main Results:

• GIP infusion significantly increased the reduction in CTX during both euglycemia and hyperglycemia compared to placebo.
• During euglycemia, GIP augmented the CTX reduction significantly (P < .001).
• During hyperglycemia, GIP infusion also significantly increased CTX reduction (P < .001), lowering CTX to 49% of basal values.

Conclusions:

• GIP administration demonstrably reduces bone resorption in humans.
• The bone resorption-reducing effect of GIP may interact with hyperglycemic conditions.
• GIP plays a role in human bone homeostasis, particularly in the postprandial state.