title: Autocrine/paracrine function of nicotinic acid adenine dinucleotide phosphate (NAADP) for glucose homeostasis in pancreatic β-cells and adipocytes.
abstract: Nicotinic acid adenine dinucleotide phosphate (NAADP) is a second messenger for mobilizing Ca(2+) from intracellular stores in various cell types. Extracellular application of NAADP has been shown to elicit intracellular Ca(2+) 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 Ca(2+)-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.
authors.affiliation: From the Department of Biochemistry.
authors.forename: Kwang-Hyun
authors.initials: KH
authors.lastname: Park
authors.forename: Byung-Ju
authors.initials: BJ
authors.lastname: Kim
authors.forename: Asif Iqbal
authors.initials: AI
authors.lastname: Shawl
authors.forename: Myung-Kwan
authors.initials: MK
authors.lastname: Han
authors.forename: Hon Cheung
authors.initials: HC
authors.lastname: Lee
authors.forename: Uh-Hyun
authors.initials: UH
authors.lastname: Kim
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D019898:Autocrine Communication; D001693:Biological Transport, Active; D020013:Calcium Signaling; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051379:Mice; D009249:NADP / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D019899:Paracrine Communication; D015290:Second Messenger Systems
chemical_list: D007328:Insulin; D009249:NADP; C024376:NAADP; D005947:Glucose
keywords: Adipocyte; Beta Cell; Calcium Signaling; Diabetes; NAADP