Workgroup Kuhn


    Actions of the NP/GC-A System on the endocrine pancreas

    Beatrice Dankworth and Michaela Kuhn, in collaboration with Ana Ropero (Institute of Bioengineering, Miguel Hernández University, Elche, Spain)

    The islet of Langerhans is the main tissue involved in maintaining blood glucose homeostasis, and its dysfunction is an essential factor in the development of type 1 and type 2 diabetes mellitus. Glucose-stimulated insulin secretion in pancreatic β-cells is driven by the ATP-dependent potassium (KATP) channels and calcium entry.

    Together with published reports our immunohistochemical studies show that the guanylyl cyclase-A (GC-A) receptor is present in pancreatic β-cells but the function is largely unknown.  Our collaborative study with Ana Ropero in isolated murine pancreatic islets and β-cells showed a direct effect of the GC-A receptor in regulating glucose-stimulated insulin secretion (GSIS) and beta-cell mass. GC-A activation by ANP, rapidly blocked ATP-dependent potassium (KATP) channel activity, increased glucose-elicited Ca2+ signals, and enhanced GSIS in islets of Langerhans. Cell type specific deletion of murine GC-A in the endocrine pancreas will help us to elucidate the relevance of these observations for systemic glucose homeostasis and metabolism.

    GC-A is present in pancreatic beta-cells. left: immunoreactive GC-A, center: immunoreactive insulin, right: merge (Ana Ropero, Elche, Spain).


    Soriano S, Ropero AB, Alonso-Magdalena P, Ripoll C, Quesada I, Gassner B, Kuhn M, Gustafsson JA, Nadal A. (2009) Rapid regulation of K(ATP) channel activity by 17{beta}-estradiol in pancreatic {beta}-cells involves the estrogen receptor {beta} and the atrial natriuretic peptide receptor. Mol Endocrinol 23:1973-1982.

    Ropero AB, Soriano S, Tudurí E, Marroquí L, Téllez N, Gassner B, Juan-Picó P, Montaya E, Quesada I, Kuhn M, Nadal A. (2010) The atrial natriuretic peptide (ANP) and guanylyl cyclase-A system modulates pancreatic ß-cell function. Endocrinology 151:3665-3674.