Generation of Nicotinic Acid Adenine Dinucleotide Phosphate and Cyclic ADP-Ribose by Glucagon-Like Peptide-1 Evokes Ca2+ Signal That Is Essential for Insulin Secretion in Mouse Pancreatic Islets

• DOI: 10.2337/db07-0443
• Publication Date: 2008-01-10T02:21:06Z
• Authors: Byung-Ju Kim; Kwang-Hyun Park; Chang-Yeol Yim; Shin Takasawa; Hiroshi Okamoto; Mie-Jae Im; Uh-Hyun Kim
• Keywords: Pancreatic Islets; Cyclic ADP-Ribose

Glucagon-like peptide-1 (GLP-1) increases intracellular Ca(2+) concentrations ([Ca(2+)](i)), resulting in insulin secretion from pancreatic beta-cells. The molecular mechanism(s) of the GLP-1-mediated regulation [Ca(2+)](i) was investigated.GLP-1-induced changes were measured beta-cells isolated Cd38(+/+) and Cd38(-/-) mice. Calcium-mobilizing second messengers identified by measuring levels nicotinic acid adenine dinucleotide phosphate (NAADP) cyclic ADP-ribose (ADPR), using a enzymatic assay. To locate NAADP- ADPR-producing enzyme(s), cellular organelles separated sucrose gradient method.A GLP-1-induced increase showed cooperative signal, i.e., an initial rise mediated action NAADP that produced acidic subsequent long-lasting ADPR plasma membranes secretory granules. GLP-1 sequentially stimulated production through protein kinase A cAMP-regulated guanine nucleotide exchange factor II. Furthermore, results governed overall signals, including GLP-1, addition to CD38, enzymes capable synthesizing and/or present These observations supported study with beta-cells, demonstrating NAADP, ADPR, signal normal GLP-1.Our findings demonstrate for is spatiotemporally formed multiple enzymes.