Atrial Natriuretic Peptide Affects Stimulus-Secretion Coupling of Pancreatic beta-Cells

作者：Undank Sabrina; Kaiser Julia; Sikimic Jelena; Duefer Martina; Krippeit Drews Peter; Drews Gisela^*

来源：Diabetes, 2017, 66(11): 2840-2848.

DOI：10.2337/db17-0392

Atrial natriuretic peptide (ANP) influences glucose homeostasis and possibly acts as a link between the cardiovascular system and metabolism, especially in metabolic disorders like diabetes. The current study evaluated effects of ANP on -cell function by the use of a beta-cell-specific knockout of the ANP receptor with guanylate cyclase activity (GC-A-KO). ANP augmented insulin secretion at the threshold glucose concentration of 6 mmol/L and decreased K-ATP single-channel activity in beta-cells of control mice but not of GC-A-KO mice. In wild-type beta-cells but not beta-cells lacking functional K-ATP channels (SUR1-KO), ANP increased electrical activity, suggesting no involvement of other ion channels. At 6 mmol/L glucose, ANP readily elicited Ca2+ influx in control beta-cells. This effect was blunted in beta-cells of GC-A-KO mice, and the maximal cytosolic Ca2+ concentration was lower. Experiments with inhibitors of protein kinase G (PKG), protein kinase A (PKA), phosphodiesterase 3B (PDE3B), and a membrane-permeable cyclic guanosine monophosphate (cGMP) analog on K-ATP channel activity and insulin secretion point to participation of the cGMP/PKG and cAMP/PKA/Epac (exchange protein directly activated by cAMP) directly activated by cAMP Epac pathways in the effects of ANP on beta-cell function; the latter seems to prevail. Moreover, ANP potentiated the effect of glucagon-like peptide 1 (GLP-1) on glucose-induced insulin secretion, which could be caused by a cGMP-mediated inhibition of PDE3B, which in turn reduces cAMP degradation.

• 出版日期2017-11-1