Endocrine Abstracts (2009) 20 OC4.5

Regulation of obestatin levels during unacylated ghrelin infusions in normal and type 2 diabetic patients

David H St-Pierre, Fabio Settanni, Ilaria Olivetti, Elena Gramaglia, Andrea Benso, Fabrizio Riganti, Ezio Ghigo & Fabio Broglio


University of Turin, Turin, Piemont, Italy.


Background: Obestatin, a ghrelin gene product was recently isolated but important questions remain regarding its regulation and its physiological effects. The aim of the present study was to evaluate the effect of unacylated ghrelin (UAG) on obestatin levels in normal subjects and patients with type 2 diabetes (T2D).

Methods: Five normal subjects and 5 T2D patients were included in this study. Unacylated ghrelin (3 μg/kg per hour) or saline were continuously administrated i.v. for 5 h and a standardized lunch was served after 2 h of infusion (0 min). Blood samples were collected at −15, 15, 30, 45, 60, 90, 120, 150 and 180 min and obestatin, insulin, glycemic and FFA levels were assayed.

Results: Before meal, UAG or saline treatments did not induce a significant change in individual groups. However, obestatin levels were significantly increased in normal subjects versus T2D patients (P=0.04) following UAG pre-treatment. In postprandial conditions, a significant decrease in obestatin levels was observed at times 60, 90, 120, 150 and 180 min in normal subjects during saline infusion. In addition, nadir and AUC values were both significantly elevated during treatment with UAG versus saline in normal subjects (P<0.05). Likewise, during treatment with UAG, peak, nadir and AUC values were significantly higher in normal subjects versus T2D patients (P<0.001).

Conclusion: This study is first to describe that the postprandial reduction of obestatin is abolished by a UAG infusion in normal subjects but not in T2D patients. Overall the present results suggest that UAG upregulates obestatin expression from the ghrelin gene only in normal subjects. Further studies will be needed to describe the mechanisms underlying the regulation of obestatin in normal subjects and T2D patients.

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