Does Somatostatin Confer Insulinostatic Effects of... : Pancreas (original) (raw)

Original Articles

Does Somatostatin Confer Insulinostatic Effects of Neuromedin U in the Rat Pancreas?

Kaczmarek, Przemyslaw PhD*; Malendowicz, Ludwik K. MD, PhD†; Fabis, Marzena PhD*‡; Ziolkowska, Agnieszka MD, PhD†; Pruszynska-Oszmalek, Ewa PhD*; Sassek, Maciej MSc*; Wojciechowicz, Tatiana PhD*; Szczepankiewicz, Dawid MSc*; Andralojc, Karolina MSc*; Szkudelski, Tomasz PhD*; Strowski, Mathias Z. MD, PhD§; Nowak, Krzysztof W. PhD, DSc*

From the *Department of Animal Physiology and Biochemistry, August Cieszkowski University of Agriculture; †Department of Histology and Embryology, Karol Marcinkowski Medical University, Poznan, Poland; ‡Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA; and §Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Interdisziplinäres Stoffwechsel-Centrum: Endokrinologie, Diabetes und Stoffwechsel, Charité-Universitätsmedizin Berlin, Germany.

Received for publication October 18, 2006; accepted February 12, 2008.

Reprints: Przemyslaw Kaczmarek, PhD, Department of Animal Physiology and Biochemistry, August Cieszkowski University of Agriculture, 35 Wolynska St, 60-637 Poznan, Poland (e-mail: [email protected]).

Dr Strowski was supported by the Deutsche Forschungsgemeinschaft.

Abstract

Objectives:

Neuromedin U (NmU) is a neuropeptide with anorexigenic activity. Two receptor subtypes (NmUR1 and NmUR2) confer the effects of NmU on target cells. We have recently demonstrated that NmU reduces insulin secretion from isolated pancreatic islets. Aim of our current study is to investigate the role of somatostatin at mediating the effects of NmU on insulin secretion.

Methods:

Expression of NmU in the pancreas was detected by immunohistochemistry. Insulin and somatostatin secretion from in situ perfused rat pancreas and isolated pancreatic islets was measured by radioimmunoassay. The paracrine effects of somatostatin within pancreatic islets were blocked by cyclosomatostatin, a somatostatin receptor antagonist.

Results:

Receptor subtype NmUR1, but not NmUR2, was expressed in the endocrine pancreas, predominantly in the periphery. Neuromedin U reduced insulin secretion from in situ perfused rat pancreas and stimulated somatostatin secretion from isolated pancreatic islets. Neuromedin U stimulated somatostatin secretion at both physiological and supraphysiological glucose concentrations. Cyclosomatostatin increased insulin secretion and reduced NmU-induced inhibition of insulin secretion.

Conclusions:

Neuromedin U reduces insulin and increases somatostatin secretion. Blockade of somatostatin action abolishes the inhibition of insulin secretion by NmU. The results of the study suggest that somatostatin mediates the inhibitory action of NmU on insulin secretion.