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

Abstract

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 z5 mmol/l), and iii) hyperinsulinemic hypoglycemia (HH) (bolus insulin 0.1 IE/kg i.v.). Results: HH and HE suppressed AG concentrations at tZ45-60 min as compared with CTR (P!0.05). At tZ90 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 tZ45 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 z1 h in response to hypoglycemia, suggesting a potential counterregulatory role of AG.

Ghrelin Protects Against Insulin-Induced Hypoglycemia in a Mouse Model of Type 1 Diabetes Mellitus

“…Basal plasma ghrelin in STZ-treated WT mice ( Figure 2D ) was significantly higher than levels usually observed in non-STZ-treated WT mice, as expected ( 34 – 41 ). Also as expected from other studies that examined the effects of insulin on plasma ghrelin or ghrelin secretion ( 41 , 53 – 57 ), plasma ghrelin fell (~79%) in STZ-treated WT mice over the course of the clamp ( Figure 2D ). Nonetheless, plasma ghrelin remained much higher than the essentially undetectable level in ghrelin-KO littermates ( Figure 2D ).…”

Effect of basal insulin therapy on vascular endothelial function and adipokine profiles in people with Type 2 diabetes

“…These results suggest that glargine's suppression of ghrelin levels might attenuate the improvement in vascular endothelial function resulting from glycaemic control. A previous study showed that insulin injection suppressed acyl ghrelin levels, even in healthy euglycaemic adults [30], suggesting that insulin may depress ghrelin excretion. In the present study, acyl ghrelin level was significantly decreased by glargine treatment but not detemir treatment.…”

Effects of ghrelin in energy balance and body weight homeostasis

“…A recent study in healthy volunteers demonstrated that acylated ghrelin levels are low under hyperinsulinemia conditions, followed by a subsequent increase in plasma ghrelin levels. 89 The authors even suggested that this fluctuation in ghrelin levels in response to acute hyperinsulemia would contribute to a rise of hunger sensation and therefore of food intake which are indeed observed after episodes of hypoglycemia. 89 Studies in animal models have demonstrated that ghrelin increases hepatic glucose production 62 by activating the gluconeogenic processes and/or via GH (which in its turn causes an increased hepatic glucose production).…”