title: Involvement of actin filament in the generation of Ca2+ mobilizing messengers in glucose-induced Ca2+ signaling in pancreatic β-cells.
abstract: Glucose is a metabolic regulator of insulin secretion from pancreatic β-cells, which is regulated by intracellular Ca(2+) signaling. We and others previously demonstrated that glucose activates CD38/ADP-ribosyl cyclase (ADPR-cyclase) to produce two Ca(2+) second messengers, cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP). Although F-actin remodeling is known to be an important step in glucose stimulated insulin secretion, the role of actin cytoskeleton in regulating Ca(2+) signaling in pancreatic β-cells remain to be solved. Here, we show that actin filaments are involved in the activation of CD38/ADPR-cyclase in pancreatic β-cells. Glucose induces a sequential formation of cADPR and NAADP. Pretreatment with jasplakinolide, an actin polymerizing agent, or a myosin heavy chain IIA (MHCIIA) blocker, blebbistatin, inhibited glucose-induced CD38 internalization, an essential step for cADPR formation. Blocking actin disassembly with jasplakinolide also abrogates glucose-induced cADPR and NAADP formation and sustained Ca(2+) signals. These results indicate that actin filaments along with MHCIIA play an important role in CD38 internalization for the generation of Ca(2+) mobilizing messengers for glucose-induced Ca(2+) signaling in pancreatic β-cells.
authors.affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonju, South Korea.
authors.forename: Asif Iqbal
authors.initials: AI
authors.lastname: Shawl
authors.forename: Kwang-Hyun
authors.initials: KH
authors.lastname: Park
authors.forename: Byung-Ju
authors.initials: BJ
authors.lastname: Kim
authors.forename: Chiharu
authors.initials: C
authors.lastname: Higashida
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Higashida
authors.forename: Uh-Hyun
authors.initials: UH
authors.lastname: Kim
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D047630:Depsipeptides / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006651:Histocytochemistry; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009249:NADP / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000199:Actins; D047630:Depsipeptides; D006576:Heterocyclic Compounds, 4 or More Rings; C057531:jasplakinolide; C472645:blebbistatin; D009249:NADP; C024376:NAADP; D036541:ADP-ribosyl Cyclase; D005947:Glucose