Sulfonylurea-mediated stimulation of insulin exocytosis via an ATP-sensitive K+ channel-independent action.
Several reports indicate that hypoglycemic sulfonylureas augment Ca(2+)-dependent insulin secretion via mechanisms other than inhibition of the ATP-sensitive K(+) channel. The effect involves a 65-kd protein in the granule membrane and culminates in intragranular acidification. Lowering of granule p...
| Main Authors: | , , , |
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| Format: | Conference item |
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2002
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| _version_ | 1797050236816850944 |
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| author | Renström, E Barg, S Thévenod, F Rorsman, P |
| author_facet | Renström, E Barg, S Thévenod, F Rorsman, P |
| author_sort | Renström, E |
| collection | OXFORD |
| description | Several reports indicate that hypoglycemic sulfonylureas augment Ca(2+)-dependent insulin secretion via mechanisms other than inhibition of the ATP-sensitive K(+) channel. The effect involves a 65-kd protein in the granule membrane and culminates in intragranular acidification. Lowering of granule pH is necessary for the insulin granule to gain release competence. Proton pumping into the granule is driven by a v-type H(+)-ATPase, but requires simultaneous Cl(-) uptake into the granule via metabolically regulated ClC-3 Cl(-) channels to maintain electroneutrality. Here we discuss the possibility that modulation of granule ClC-3 channels represents the mechanism whereby sulfonylureas directly potentiate the beta-cell exocytotic machinery. |
| first_indexed | 2024-03-06T18:02:11Z |
| format | Conference item |
| id | oxford-uuid:002863ae-8970-43ea-ae90-1b0a6a3872f1 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T18:02:11Z |
| publishDate | 2002 |
| record_format | dspace |
| spelling | oxford-uuid:002863ae-8970-43ea-ae90-1b0a6a3872f12022-03-26T08:28:03ZSulfonylurea-mediated stimulation of insulin exocytosis via an ATP-sensitive K+ channel-independent action.Conference itemhttp://purl.org/coar/resource_type/c_5794uuid:002863ae-8970-43ea-ae90-1b0a6a3872f1Symplectic Elements at Oxford2002Renström, EBarg, SThévenod, FRorsman, PSeveral reports indicate that hypoglycemic sulfonylureas augment Ca(2+)-dependent insulin secretion via mechanisms other than inhibition of the ATP-sensitive K(+) channel. The effect involves a 65-kd protein in the granule membrane and culminates in intragranular acidification. Lowering of granule pH is necessary for the insulin granule to gain release competence. Proton pumping into the granule is driven by a v-type H(+)-ATPase, but requires simultaneous Cl(-) uptake into the granule via metabolically regulated ClC-3 Cl(-) channels to maintain electroneutrality. Here we discuss the possibility that modulation of granule ClC-3 channels represents the mechanism whereby sulfonylureas directly potentiate the beta-cell exocytotic machinery. |
| spellingShingle | Renström, E Barg, S Thévenod, F Rorsman, P Sulfonylurea-mediated stimulation of insulin exocytosis via an ATP-sensitive K+ channel-independent action. |
| title | Sulfonylurea-mediated stimulation of insulin exocytosis via an ATP-sensitive K+ channel-independent action. |
| title_full | Sulfonylurea-mediated stimulation of insulin exocytosis via an ATP-sensitive K+ channel-independent action. |
| title_fullStr | Sulfonylurea-mediated stimulation of insulin exocytosis via an ATP-sensitive K+ channel-independent action. |
| title_full_unstemmed | Sulfonylurea-mediated stimulation of insulin exocytosis via an ATP-sensitive K+ channel-independent action. |
| title_short | Sulfonylurea-mediated stimulation of insulin exocytosis via an ATP-sensitive K+ channel-independent action. |
| title_sort | sulfonylurea mediated stimulation of insulin exocytosis via an atp sensitive k channel independent action |
| work_keys_str_mv | AT renstrome sulfonylureamediatedstimulationofinsulinexocytosisviaanatpsensitivekchannelindependentaction AT bargs sulfonylureamediatedstimulationofinsulinexocytosisviaanatpsensitivekchannelindependentaction AT thevenodf sulfonylureamediatedstimulationofinsulinexocytosisviaanatpsensitivekchannelindependentaction AT rorsmanp sulfonylureamediatedstimulationofinsulinexocytosisviaanatpsensitivekchannelindependentaction |