Characterization of Somatostatin Receptor Subtype-Specific Regulation of Insulin and Glucagon Secretion: An in Vitro Study on Isolated Human Pancreatic Islets
V Singh, MD Brendel, S Zacharias… - The Journal of …, 2007 - academic.oup.com
V Singh, MD Brendel, S Zacharias, S Mergler, H Jahr, B Wiedenmann, RG Bretzel…
The Journal of Clinical Endocrinology & Metabolism, 2007•academic.oup.comAbstract Introduction: Pancreatic A-and B-cells express somatostatin receptors (SSTRs).
Five pharmacologically distinct SSTR subtypes are known (SSTR1–SSTR5). In rodents,
SSTR2 inhibits glucagon secretion, whereas SSTR5 suppresses the release of insulin.
Human pancreatic A-and B-cells express SSTR1–3 and SSTR5; however, their contribution
to the regulation of glucagon and insulin secretion is not well known. Aim of the Study: The
goal of this study was to characterize the role of individual SSTR subtypes in regulating …
Five pharmacologically distinct SSTR subtypes are known (SSTR1–SSTR5). In rodents,
SSTR2 inhibits glucagon secretion, whereas SSTR5 suppresses the release of insulin.
Human pancreatic A-and B-cells express SSTR1–3 and SSTR5; however, their contribution
to the regulation of glucagon and insulin secretion is not well known. Aim of the Study: The
goal of this study was to characterize the role of individual SSTR subtypes in regulating …
Abstract
Introduction: Pancreatic A- and B-cells express somatostatin receptors (SSTRs). Five pharmacologically distinct SSTR subtypes are known (SSTR1–SSTR5). In rodents, SSTR2 inhibits glucagon secretion, whereas SSTR5 suppresses the release of insulin. Human pancreatic A- and B-cells express SSTR1–3 and SSTR5; however, their contribution to the regulation of glucagon and insulin secretion is not well known.
Aim of the Study: The goal of this study was to characterize the role of individual SSTR subtypes in regulating human glucagon and insulin secretion in vitro.
Methods: Human pancreatic islets were isolated from healthy donors and incubated with somatostatin, SSTR1–3-selective and SSTR5-selective agonists, or an SSTR2-selective antagonist (DC-41-33). Stimulation of insulin secretion was induced by glucose (10, 20 mm) alone or in combination with 10 nm exendin-4 or 10 mml-arginine. Glucagon secretion was induced by 20 mml-arginine. Basal secretion of insulin and glucagon was measured at 2.8 or 3.3 mm glucose.
Results: SSTR1-, SSTR2-, and SSTR5-selective agonists inhibited insulin secretion with the following order of potency: SSTR2 (EC50, 0.08 nm) > SSTR5 (EC50, 5.3 nm) > SSTR1 (EC50, 35 nm). Glucagon secretion was inhibited by SSTR-selective agonists with the following order of potency: SSTR2 (EC50, 0.05 nm) > SSTR1 (EC50, 1.8 nm) > SSTR5 (EC50, 28 nm). DC-41-33 dose-dependently reversed the effects of the SSTR2-selective agonist on insulin and glucagon secretion.
Conclusion: Our study demonstrates that SSTR2-agonist is the most potent inhibitor of insulin and glucagon secretion from isolated human pancreatic islets. Furthermore, we identify SSTR1- and SSTR5-selective agonists as additional inhibitors of insulin and glucagon secretion from human pancreas.
Oxford University Press