Endocrine Abstracts

Objectives: Atrial natriuretic peptide (ANP) is a cardiac hormone that is known to play an essential role in regulation of blood pressure and vascular endothelial function. However, the metabolic regulation of ANP is not fully understood. In patients with the metabolic syndrome, hyperglucagonemia is a common feature, besides hypertension and hyperinsulinemia. Our aim was to evaluate the impact of glucagon on proANP and the possible mechanisms underlying this effect.

Methods: In this prospective, double-blind, placebo-controlled study, we studied hormonal and metabolic responses to intramuscular glucagon or placebo administration in 13 patients with type 1 diabetes mellitus (DM1; 6/7 males/females; BMI 24.8±0.95 kg/m²), in 12 obese healthy subjects (OS; 6/6; 33.9±1.6 kg/m²) and in 13 lean controls (LC; 6/7; 21.6±0.5 kg/m²). Furthermore, we studied the response of proANP to insulin (0.15 IU/kg BW) in OS and LC as a possible mediator for the glucagon-induced effects using insulin tolerance test. Finally, we further investigated the impact of hyperinsulinemia under euglycemic conditions on proANP in 32 healthy subjects.

Results: Gender, fasting glucose and glucagon levels were comparable between groups. Glucagon significantly decreased proANP in OS (proANP-AUC240: 203.4±4.8 (glucagon) vs. 226.6±6.9 (placebo), P<0.01) and LC (205.8±2.6 vs 245.8±9.2, P<0.01) but failed to affect proANP concentrations in DM1 (P=0.737). Glucagon increased insulin in LS and OS (P<0.01) but did not affect it in DM1 (P>0.05).

Under hypoglycaemic hyperinsulinemic conditions, insulin markedly decreased proANP in OS and LC (P<0.01). Similarly, insulin significantly decreased proANP under euglycemic hyperinsulinemic conditions in healthy subjects (P<0.01).

Conclusions: We show that insulin mediates the glucagon-induced decrease in proANP, possibly providing a novel link between hyperinsulinemia and cardiovascular risk.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.