Circulating acylghrelin levels are suppressed by insulin and increase in response to hypoglycemia in healthy adult volunteers.

Objective: Ghrelin has glucoregulatory and orexigenic actions, but its role in acute hypoglycemia remains uncertain. We aimed to investigate circulating levels of acylghrelin (AG) and unacylated ghrelin (UAG) in response to hyperinsulinemia and to hypoglycemia.

Design: A randomized, single-blind, placebo-controlled crossover study including 3 study days was performed at a university hospital clinical research center.

Methods: Nine healthy men completed 3 study days: i) saline control (CTR), ii) hyperinsulinemic euglycemia (HE) (bolus insulin 0.1 IE/kg i.v. and glucose 20% i.v. for 105 min, plasma glucose ≈5 mmol/l), and iii) hyperinsulinemic hypoglycemia (HH) (bolus insulin 0.1 IE/kg i.v.).

Results: HH and HE suppressed AG concentrations at t=45-60 min as compared with CTR (P<0.05). At t=90 min, a rebound increase in AG was observed in response to HH as compared with both HE and CTR (P<0.05). UAG also decreased during HH and HE at t=45 min (P<0.05), whereas the AG-to-UAG ratio remained unaffected.

Conclusions: This study demonstrates that AG and UAG are directly suppressed by hyperinsulinemia and that AG concentrations increase after a latency of ≈1 h in response to hypoglycemia, suggesting a potential counterregulatory role of AG.