NAADP: a new second messenger for glucose-induced Ca2+ responses in clonal pancreatic beta cells.
Important questions remain concerning how elevated blood glucose levels are coupled to insulin secretion from pancreatic beta cells and how this process is impaired in type 2 diabetes. Glucose uptake and metabolism in beta cells cause the intracellular Ca(2+) concentration ([Ca(2+)](i)) to increase...
| Main Authors: | , , , , |
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| Formato: | Journal article |
| Idioma: | English |
| Publicado em: |
2003
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| _version_ | 1826263803087552512 |
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| author | Masgrau, R Churchill, G Morgan, A Ashcroft, S Galione, A |
| author_facet | Masgrau, R Churchill, G Morgan, A Ashcroft, S Galione, A |
| author_sort | Masgrau, R |
| collection | OXFORD |
| description | Important questions remain concerning how elevated blood glucose levels are coupled to insulin secretion from pancreatic beta cells and how this process is impaired in type 2 diabetes. Glucose uptake and metabolism in beta cells cause the intracellular Ca(2+) concentration ([Ca(2+)](i)) to increase to a degree necessary and sufficient for triggering insulin release. Although both Ca(2+) influx and Ca(2+) release from internal stores are critical, the roles of inositol 1,4,5-trisphosphate (IP(3)) and cyclic adenosine dinucleotide phosphate ribose (cADPR) in regulating the latter have proven equivocal. Here we show that glucose also increases [Ca(2+)](i) via the novel Ca(2+)-mobilizing agent nicotinic acid adenine dinucleotide phosphate (NAADP) in the insulin-secreting beta-cell line MIN6. NAADP binds to specific, high-affinity membrane binding sites and at low concentrations elicits robust Ca(2+) responses in intact cells. Higher concentrations of NAADP inactivate NAADP receptors and attenuate the glucose-induced Ca(2+) increases. Importantly, glucose stimulation increases endogenous NAADP levels, providing strong evidence for recruitment of this pathway. In conclusion, our results support a model in which NAADP mediates glucose-induced Ca(2+) signaling in pancreatic beta cells and are the first demonstration in mammalian cells of the presence of endogenous NAADP levels that can be regulated by a physiological stimulus. |
| first_indexed | 2024-03-06T19:57:38Z |
| format | Journal article |
| id | oxford-uuid:2631d45e-d593-47a6-92aa-a1c74c8d38ba |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:57:38Z |
| publishDate | 2003 |
| record_format | dspace |
| spelling | oxford-uuid:2631d45e-d593-47a6-92aa-a1c74c8d38ba2022-03-26T11:59:29ZNAADP: a new second messenger for glucose-induced Ca2+ responses in clonal pancreatic beta cells.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2631d45e-d593-47a6-92aa-a1c74c8d38baEnglishSymplectic Elements at Oxford2003Masgrau, RChurchill, GMorgan, AAshcroft, SGalione, AImportant questions remain concerning how elevated blood glucose levels are coupled to insulin secretion from pancreatic beta cells and how this process is impaired in type 2 diabetes. Glucose uptake and metabolism in beta cells cause the intracellular Ca(2+) concentration ([Ca(2+)](i)) to increase to a degree necessary and sufficient for triggering insulin release. Although both Ca(2+) influx and Ca(2+) release from internal stores are critical, the roles of inositol 1,4,5-trisphosphate (IP(3)) and cyclic adenosine dinucleotide phosphate ribose (cADPR) in regulating the latter have proven equivocal. Here we show that glucose also increases [Ca(2+)](i) via the novel Ca(2+)-mobilizing agent nicotinic acid adenine dinucleotide phosphate (NAADP) in the insulin-secreting beta-cell line MIN6. NAADP binds to specific, high-affinity membrane binding sites and at low concentrations elicits robust Ca(2+) responses in intact cells. Higher concentrations of NAADP inactivate NAADP receptors and attenuate the glucose-induced Ca(2+) increases. Importantly, glucose stimulation increases endogenous NAADP levels, providing strong evidence for recruitment of this pathway. In conclusion, our results support a model in which NAADP mediates glucose-induced Ca(2+) signaling in pancreatic beta cells and are the first demonstration in mammalian cells of the presence of endogenous NAADP levels that can be regulated by a physiological stimulus. |
| spellingShingle | Masgrau, R Churchill, G Morgan, A Ashcroft, S Galione, A NAADP: a new second messenger for glucose-induced Ca2+ responses in clonal pancreatic beta cells. |
| title | NAADP: a new second messenger for glucose-induced Ca2+ responses in clonal pancreatic beta cells. |
| title_full | NAADP: a new second messenger for glucose-induced Ca2+ responses in clonal pancreatic beta cells. |
| title_fullStr | NAADP: a new second messenger for glucose-induced Ca2+ responses in clonal pancreatic beta cells. |
| title_full_unstemmed | NAADP: a new second messenger for glucose-induced Ca2+ responses in clonal pancreatic beta cells. |
| title_short | NAADP: a new second messenger for glucose-induced Ca2+ responses in clonal pancreatic beta cells. |
| title_sort | naadp a new second messenger for glucose induced ca2 responses in clonal pancreatic beta cells |
| work_keys_str_mv | AT masgraur naadpanewsecondmessengerforglucoseinducedca2responsesinclonalpancreaticbetacells AT churchillg naadpanewsecondmessengerforglucoseinducedca2responsesinclonalpancreaticbetacells AT morgana naadpanewsecondmessengerforglucoseinducedca2responsesinclonalpancreaticbetacells AT ashcrofts naadpanewsecondmessengerforglucoseinducedca2responsesinclonalpancreaticbetacells AT galionea naadpanewsecondmessengerforglucoseinducedca2responsesinclonalpancreaticbetacells |