ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 P532

Diabetogenic effects of a continuous infusion of acylated ghrelin in normal and type 2 diabetic patients

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

University of Turin, Torino, Italy.

Background: Previous studies have shown that acylated ghrelin (AG) modulates insulin secretion and glucose disposal in vitro and after acute administration in humans. The aim of the present study was to evaluate postprandial glucose and insulin response following AG infusion in normal subjects and patients with type 2 diabetes.

Methods: Six normal subjects and 3 patients with type 2 diabetes were included in this study. AG (1 μg/kg per h) or saline were continuously administrated iv for 5 h and a standardized lunch of ~920 Kcal (50% carbohydrates, 30% lipids and 20% protein content) was served after 2 h of infusion. Blood samples were collected at times 0, 15, 30, 45, 60, 90, 120, 150 and 180 min in order to assay insulin levels and glycemia.

Results: Before meal, insulin levels (saline: 12.7±3.3 μIU/ml; AG: 13.1±6.6 μIU/ml) and glycemia (saline: 70.8±6.8 mg/dl; AG: 75.3±9.1) were not significantly different for both treatments. In postprandial conditions, AG infusion upregulated the glycemic peak value (153.2±22.6 mg/dl vs 110.0±9.3; P=0.03) while insulin concentrations were marginally increased (205.9±114.5 μIU/ml vs 96.3±17.2 μIU/ml; P>0.05) when compared with saline. Continuous AG administration induced a significantly increased of glycemic AUC (22 041±3758 mg/dl per min vs 15 273±834 mg/dl per min) while insulin AUC (24 959±13 310 μIU/ml per min vs 10 027±1933 μIU/ml per min; P>0.05) tended to be elevated compared to the one observed during saline administration. In addition, preliminary data suggest that AG infusion could also confer detrimental effects (increased insulin secretion and elevation of glycemia) in patients with early onset of type 2 diabetes.

Conclusion: The present study is the first to evaluate the influence of AG infusion in postprandial conditions both in normal subjects and patients with type 2 diabetes. Finally, these results strongly suggest that continuous administration of AG induces diabetogenic effects.

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