Effect of Exogenous Intravenous Administrations of GLP-1 and/or GIP on Circulating Pro-Atrial Natriuretic Peptide in Subjects With Different Stages of Glucose Tolerance

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Abstract
GLP-1 receptor agonists have antihypertensive properties, explained via release of atrial natriuretic peptide (ANP) as shown in mice (1). Whether GLP-1 directly interacts with the natriuretic peptide system in humans was studied in a single report (2). Here, we studied interaction of two major incretins, glucose-dependent insulinotropic peptide (GIP) and GLP-1, both administered exogenously, with ANP in patients with type 2 diabetes (nine men and three women, 61 ± 10 years, BMI 30.0 ± 3.7 kg/m2, HbA1c 7.3 ± 1.5%). Placebo (vehicle: 0.9% NaCl with 1% human serum albumin), GIP (4 pmol · kg−1 · min−1), GLP-1(7–36)-amide (1.2 pmol · kg−1 · min−1), or a combination of both hormones were infused over 360 min on different days in randomized order (3). Additionally, eight male overweight subjects with normal glucose tolerance (49.9 ± 3.2 years, BMI 32.9 ± 0.7 kg/m2) were given GIP infusion (2 pmol · kg−1 · min−1) and placebo (isotonic saline) infusion for 240 min (4). In cohort I, intact, biologically active GIP and GLP-1 were measured as described previously (3). In cohort II, total GIP was determined by commercial ELISA kit (Linco Research, St. Charles, MO). Midregional pro-ANP (MR-proANP) was measured with an immunoassay (MR-proANP LIA; B.R.A.H.M.S GmbH, Hennigsdorf, Germany). In subjects with type 2 diabetes, exogenous GIP elevated the total concentrations of GIP …