Desacyl ghrelin is influenced by changes in insulin concentration during an insulin tolerance test

Objective: Ghrelin, a gut-brain peptide, regulates energy homeostasis and glucose metabolism and is present in acylated and nonacylated form in the circulation. Although desacyl ghrelin (DAG), the predominant form of ghrelin, is associated with insulin sensitivity and improved metabolic state, not much is known about its direct regulation by insulin. We aimed to assess changes in DAG in response to the rapid increase in insulin concentration during an insulin tolerance test (ITT) in normal weight and obese subjects. Design: We performed an observational single center study. An ITT was assessed in eight subjects (four males), median age of 29.9 years (range 19.6-42.0). DAG concentrations were measured at 20, 40, 60 and 90. min after insulin infusion. Homeostatic Model Assessment (HOMA) was calculated from fasting insulin and glucose. Body mass index (BMI) and waist circumference were assessed. Results: Three subjects were obese (BMI≥30kg/m²), one subject was overweight (BMI=25-30kg/m²) and four subjects had normal weight (BMI=18.5-25kg/m²). Median DAG decreased after insulin infusion (90pg/mL, p=0.028), especially in normal weight subjects. Baseline DAG was lower in subjects with higher BMI (ρ=-0.76, p=0.028) and higher fasting insulin (ρ=-0.76, p=0.030). DAG changes correlated with fasting insulin levels (ρ=-0.85, p=0.007), HOMA (ρ=-0.86, p=0.007), BMI (ρ=-0.83, p=0.010) and waist circumference (ρ=-0.93, p<0.001). Conclusion: DAG levels rapidly decreased in response to insulin administration in normal subjects, but not in insulin-resistant obese who are in a state of relative DAG deficiency.