دورية أكاديمية
Sulfonylurea receptor type 1 knock-out mice have intact feeding-stimulated insulin secretion despite marked impairment in their response to glucose.
| العنوان: | Sulfonylurea receptor type 1 knock-out mice have intact feeding-stimulated insulin secretion despite marked impairment in their response to glucose. |
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| المؤلفون: | Shiota C; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA., Larsson O, Shelton KD, Shiota M, Efanov AM, Hoy M, Lindner J, Kooptiwut S, Juntti-Berggren L, Gromada J, Berggren PO, Magnuson MA |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 2002 Oct 04; Vol. 277 (40), pp. 37176-83. Date of Electronic Publication: 2002 Jul 30. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Print ISSN: 0021-9258 (Print) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | ATP-Binding Cassette Transporters* , Eating*/physiology , Potassium Channels, Inwardly Rectifying*, Blood Glucose/*metabolism , Insulin/*metabolism , Potassium Channels/*physiology , Receptors, Drug/*physiology, Animals ; Carbachol/pharmacology ; Cloning, Molecular ; Exocytosis ; Genotype ; Glucose Clamp Technique ; Insulin Secretion ; Islets of Langerhans/drug effects ; Islets of Langerhans/metabolism ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Perfusion ; Potassium Channels/deficiency ; Potassium Channels/genetics ; Receptors, Drug/deficiency ; Receptors, Drug/genetics ; Recombinant Proteins/metabolism ; Sulfonylurea Receptors |
| مستخلص: | The ATP-sensitive potassium channel is a key molecular complex for glucose-stimulated insulin secretion in pancreatic beta cells. In humans, mutations in either of the two subunits for this channel, the sulfonylurea type 1 receptor (Sur1) or Kir6.2, cause persistent hyperinsulinemic hypoglycemia of infancy. We have generated and characterized Sur1 null mice. Interestingly, these animals remain euglycemic for a large portion of their life despite constant depolarization of membrane, elevated cytoplasmic free Ca(2+) concentrations, and intact sensitivity of the exocytotic machinery to Ca(2+). A comparison of glucose- and meal-stimulated insulin secretion showed that, although Sur1 null mice do not secrete insulin in response to glucose, they secrete nearly normal amounts of insulin in response to feeding. Because Sur1 null mice lack an insulin secretory response to GLP-1, even though their islets exhibit a normal rise in cAMP by GLP-1, we tested their response to cholinergic stimulation. We found that perfused Sur1 null pancreata secreted insulin in response to the cholinergic agonist carbachol in a glucose-dependent manner. Together, these findings suggest that cholinergic stimulation is one of the mechanisms that compensate for the severely impaired response to glucose and GLP-1 brought on by the absence of Sur1, thereby allowing euglycemia to be maintained. |
| معلومات مُعتمدة: | CA68485 United States CA NCI NIH HHS; DK20593 United States DK NIDDK NIH HHS; DK42502 United States DK NIDDK NIH HHS; DK42612 United States DK NIDDK NIH HHS |
| سلسلة جزيئية: | GENBANK AF037274; AF037275; AF037276; AF037277; AF037278; AF037279; AF037280; AF037281; AF037282; AF037283; AF037284; AF037285; AF037286; AF037287; AF037288; AF037289; AF037290; AF037291; AF037292; AF037293; AF037294; AF037295; AF037296; AF037297; AF037298; AF037299; AF037300; AF037301; AF037302; AF037303; AF037304; AF037305; AF037306; AF037307; AF037308; AF037309; AF037310; AF037311; AF037312; AF037313 |
| المشرفين على المادة: | 0 (ABCC8 protein, human) 0 (ATP-Binding Cassette Transporters) 0 (Abcc8 protein, mouse) 0 (Blood Glucose) 0 (Insulin) 0 (Potassium Channels) 0 (Potassium Channels, Inwardly Rectifying) 0 (Receptors, Drug) 0 (Recombinant Proteins) 0 (Sulfonylurea Receptors) 8Y164V895Y (Carbachol) |
| تواريخ الأحداث: | Date Created: 20020801 Date Completed: 20021120 Latest Revision: 20210206 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1074/jbc.M206757200 |
| PMID: | 12149271 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 0021-9258 |
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| DOI: | 10.1074/jbc.M206757200 |