Autocrine/Paracrine Function of Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) for Glucose Homeostasis in Pancreatic β-Cells and Adipocytes |
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| Authors: | Kwang-Hyun Park Byung-Ju Kim Asif Iqbal Shawl Myung-Kwan Han Hon Cheung Lee Uh-Hyun Kim |
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| Institution: | From the ‡Department of Biochemistry.;the §National Creative Research Laboratory for Ca2+ Signaling Network.;the ¶Department of Microbiology, and ;the **Institute of Cardiovascular Research, Chonbuk National University Medical School, Jeonju, 561-180, Korea and ;the ‖School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China |
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| Abstract: | Nicotinic acid adenine dinucleotide phosphate (NAADP) is a second messenger for mobilizing Ca2+ from intracellular stores in various cell types. Extracellular application of NAADP has been shown to elicit intracellular Ca2+ signals, indicating that it is readily transported into cells. However, little is known about the functional role of this NAADP uptake system. Here, we show that NAADP is effectively transported into selected cell types involved in glucose homeostasis, such as adipocytes and pancreatic β-cells, but not the acinar cells, in a high glucose-dependent manner. NAADP uptake was inhibitable by Ned-19, a NAADP mimic; dipyridamole, a nucleoside inhibitor; or NaN3, a metabolic inhibitor or under Ca2+-free conditions. Furthermore, NAADP was found to be released from pancreatic islets upon stimulation by high glucose. Consistently, administration of NAADP to type 2 diabetic mice improved glucose tolerance. We propose that NAADP is functioning as an autocrine/paracrine hormone important in glucose homeostasis. NAADP is thus a potential antidiabetic agent with therapeutic relevance. |
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| Keywords: | Adipocyte Beta Cell Calcium Signaling Diabetes NAADP |
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