1976-P: Physiological Effects of GIP(1-30)NH₂ in Healthy Subjects

The gut-derived incretin hormone glucose-dependent insulinotropic polypeptide (GIP) circulates in at least two active forms: GIP(1-42), which besides its insulinotropic effect during hyperglycemia stimulates glucagon secretion at low plasma glucose (PG) levels and decreases bone resorption, and GIP(1-30)NH₂. In vitro and rodent studies has shown similar physiological effects of GIP(1-30)NH₂ and GIP(1-42), but effects in humans remain unexplored. Here, we infused GIP(1-42) and GIP(1-30)NH₂ in humans to establish the physiological effects of GIP(1-30)NH₂.

On three separate days, 10 healthy men (mean age 23 (range 20-28) years, BMI 22.4 (20.0-25.2) kg/m²) received intravenous infusions of GIP(1-42), GIP(1-30)NH₂ and saline, respectively. Both peptides were infused at 4 pmol/kg/min during 200 minutes. After 20 minutes of infusion, PG was clamped at the fasting PG level (FPG) for 60 minutes, followed by 60 minutes at FPG × 1.5, and lastly 60 minutes at FPG × 2.

There were no differences in PG levels between the three interventions, but significantly more glucose was needed for the clamp with GIP(1-42) compared to saline (P = 0.022). Plasma levels of GIP(1-30)NH₂ reached a mean (± SD) of 31.4 ± 29.9 pmol/l and GIP(1-42) of 97.8 ± 27.9 pmol/l. Despite this difference, both infusions resulted in robust and glucose-dependent insulin responses (as assessed by serum C-peptide) with no differences between the two peptide infusions (P = 0.187), and at FPG level only GIP(1-30)NH₂ resulted in higher glucagon levels than saline (P = 0.0302). At 180 minutes, the bone resorption marker carboxy-terminal collagen I crosslinks (CTX) was suppressed to 61 ± 13% of baseline values during saline, 42 ± 16% during GIP(1-30)NH₂, and 29 ± 6% during GIP(1-42) (P < 0.001).

We conclude that, like GIP(1-42), GIP(1-30)NH₂ is a potent insulinotropic (at high PG levels), glucagonotropic (at low PG levels) and bone resorption-inhibiting hormone in healthy subjects.