Home LiteratureArticle Details
PMID: 12601083 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

SUR1 regulates PKA-independent cAMP-induced granule priming in mouse pancreatic B-cells.

The Journal of general physiology ·Vol. 121 ·No. 3 ·2003-03-00 ·Pages 181-97

Eliasson L, Ma X, Renström E, Barg S, Berggren PO, Galvanovskis J, Gromada J, Jing X, Lundquist I, Salehi A, Sewing S, Rorsman P

Abstract

Measurements of membrane capacitance were applied to dissect the cellular mechanisms underlying PKA-dependent and -independent stimulation of insulin secretion by cyclic AMP. Whereas the PKA-independent (Rp-cAMPS-insensitive) component correlated with a rapid increase in membrane capacitance of approximately 80 fF that plateaued within approximately 200 ms, the PKA-dependent component became prominent during depolarizations >450 ms. The PKA-dependent and -independent components of cAMP-stimulated exocytosis differed with regard to cAMP concentration dependence; the K(d) values were 6 and 29 micro M for the PKA-dependent and -independent mechanisms, respectively. The ability of cAMP to elicit exocytosis independently of PKA activation was mimicked by the selective cAMP-GEFII agonist 8CPT-2Me-cAMP. Moreover, treatment of B-cells with antisense oligodeoxynucleotides against cAMP-GEFII resulted in partial (50%) suppression of PKA-independent exocytosis. Surprisingly, B-cells in islets isolated from SUR1-deficient mice (SUR1(-/-) mice) lacked the PKA-independent component of exocytosis. Measurements of insulin release in response to GLP-1 stimulation in isolated islets from SUR1(-/-) mice confirmed the complete loss of the PKA-independent component. This was not attributable to a reduced capacity of GLP-1 to elevate intracellular cAMP but instead associated with the inability of cAMP to stimulate influx of Cl(-) into the granules, a step important for granule priming. We conclude that the role of SUR1 in the B cell extends beyond being a subunit of the plasma membrane K(ATP)-channel and that it also plays an unexpected but important role in the cAMP-dependent regulation of Ca(2+)-induced exocytosis.

MeSH Terms
ATP-Binding Cassette Transporters Animals Cells, Cultured Cyclic AMP/physiology Cyclic AMP-Dependent Protein Kinases/physiology Electric Capacitance Electrophysiology Exocytosis/drug effects,physiology Glucagon/pharmacology Glucagon-Like Peptide 1 Glucose/pharmacology Guanine Nucleotide Exchange Factors/agonists,physiology Insulin/metabolism Insulin Secretion Islets of Langerhans/drug effects,physiology Mice Mice, Inbred Strains Mice, Knockout Peptide Fragments/pharmacology Potassium Channels/physiology Potassium Channels, Inwardly Rectifying Protein Precursors/pharmacology Receptors, Drug/physiology Secretory Vesicles/physiology Sulfonylurea Receptors Time Factors
Chemicals
ATP-Binding Cassette Transporters Abcc8 protein, mouse Guanine Nucleotide Exchange Factors Insulin Peptide Fragments Potassium Channels Potassium Channels, Inwardly Rectifying Protein Precursors Receptors, Drug Sulfonylurea Receptors Glucagon-Like Peptide 1 Glucagon Cyclic AMP Cyclic AMP-Dependent Protein Kinases Glucose
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Eliasson Lena
Department of Molecular and Cellular Physiology, Institute of Physiological Sciences, SE-221 84 Lund, Sweden.
Ma Xiaosong
Renström Erik
Barg Sebastian
Berggren Per-Olof
Galvanovskis Juris
Gromada Jesper
Jing Xingjun
Lundquist Ingmar
Salehi Albert
Sewing Sabine
Rorsman Patrik
References (43)
43 references, click to expand
  1. Localized calcium influx in pancreatic beta-cells: its significance for Ca2+-dependent insulin secretion from the islets of Langerhans.
    Endocrine. 2000 Dec;13(3):251-62 PMID: 11216635
  2. Triggering and amplifying pathways of regulation of insulin secretion by glucose.
    Diabetes. 2000 Nov;49(11):1751-60 PMID: 11078440
  3. cAMP-regulated guanine nucleotide exchange factor II (Epac2) mediates Ca2+-induced Ca2+ release in INS-1 pancreatic beta-cells.
    J Physiol. 2001 Oct 15;536(Pt 2):375-85 PMID: 11600673
  4. Fast exocytosis with few Ca(2+) channels in insulin-secreting mouse pancreatic B cells.
    Biophys J. 2001 Dec;81(6):3308-23 PMID: 11720994
  5. Critical role of cAMP-GEFII--Rim2 complex in incretin-potentiated insulin secretion.
    J Biol Chem. 2001 Dec 7;276(49):46046-53 PMID: 11598134
  6. RIM1alpha forms a protein scaffold for regulating neurotransmitter release at the active zone.
    Nature. 2002 Jan 17;415(6869):321-6 PMID: 11797009
  7. Sulfonylurea-mediated stimulation of insulin exocytosis via an ATP-sensitive K+ channel-independent action.
    Diabetes. 2002 Feb;51 Suppl 1:S33-6 PMID: 11815455
  8. Signals and pools underlying biphasic insulin secretion.
    Diabetes. 2002 Feb;51 Suppl 1:S60-7 PMID: 11815460
  9. Beta-cell protein kinases and the dynamics of the insulin response to glucose.
    Diabetes. 2002 Feb;51 Suppl 1:S68-73 PMID: 11815461
  10. A subset of 50 secretory granules in close contact with L-type Ca2+ channels accounts for first-phase insulin secretion in mouse beta-cells.
    Diabetes. 2002 Feb;51 Suppl 1:S74-82 PMID: 11815462
  11. Inositol 3,4,5,6-tetrakisphosphate inhibits insulin granule acidification and fusogenic potential.
    J Biol Chem. 2002 Jul 26;277(30):26717-20 PMID: 12055181
  12. Sulfonylurea receptor type 1 knock-out mice have intact feeding-stimulated insulin secretion despite marked impairment in their response to glucose.
    J Biol Chem. 2002 Oct 4;277(40):37176-83 PMID: 12149271
  13. A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK.
    Nat Cell Biol. 2002 Nov;4(11):901-6 PMID: 12402047
  14. cAMP-activated protein kinase-independent potentiation of insulin secretion by cAMP is impaired in SUR1 null islets.
    Diabetes. 2002 Dec;51(12):3440-9 PMID: 12453898
  15. Glucose metabolism in mouse pancreatic islets.
    Biochem J. 1970 Jun;118(1):143-54 PMID: 4919469
  16. Regulation of insulin release by calcium.
    Physiol Rev. 1981 Oct;61(4):914-73 PMID: 6117094
  17. Electrical activity, cAMP concentration, and insulin release in mouse islets of Langerhans.
    Am J Physiol. 1985 Jan;248(1 Pt 1):C145-53 PMID: 2578253
  18. Protein phosphorylation in electrically permeabilized islets of Langerhans. Effects of Ca2+, cyclic AMP, a phorbol ester and noradrenaline.
    Biochem J. 1988 Sep 1;254(2):397-403 PMID: 2845950
  19. Establishment of a pancreatic beta cell line that retains glucose-inducible insulin secretion: special reference to expression of glucose transporter isoforms.
    Endocrinology. 1990 Jul;127(1):126-32 PMID: 2163307
  20. Electrophysiology of the pancreatic beta-cell.
    Prog Biophys Mol Biol. 1989;54(2):87-143 PMID: 2484976
  21. Pancreatic beta-cells are rendered glucose-competent by the insulinotropic hormone glucagon-like peptide-1(7-37).
    Nature. 1993 Jan 28;361(6410):362-5 PMID: 8381211
  22. Calcium-independent potentiation of insulin release by cyclic AMP in single beta-cells.
    Nature. 1993 May 27;363(6427):356-8 PMID: 7684514
  23. A low affinity Ca2+ receptor controls the final steps in peptide secretion from pituitary melanotrophs.
    Neuron. 1993 Jul;11(1):93-104 PMID: 8393324
  24. New perspectives on the actions of sulphonylureas and hyperglycaemic sulphonamides on the pancreatic beta-cell.
    Diabete Metab. 1994 Mar-Apr;20(2):157-62 PMID: 7805953
  25. Identification of synaptic proteins and their isoform mRNAs in compartments of pancreatic endocrine cells.
    Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12487-91 PMID: 7809063
  26. Kinetics of the secretory response in bovine chromaffin cells following flash photolysis of caged Ca2+.
    Biophys J. 1994 Dec;67(6):2546-57 PMID: 7696493
  27. Glucagon-like peptide I increases cytoplasmic calcium in insulin-secreting beta TC3-cells by enhancement of intracellular calcium mobilization.
    Diabetes. 1995 Jul;44(7):767-74 PMID: 7789644
  28. PKC-dependent stimulation of exocytosis by sulfonylureas in pancreatic beta cells.
    Science. 1996 Feb 9;271(5250):813-5 PMID: 8628999
  29. Cooling inhibits exocytosis in single mouse pancreatic B-cells by suppression of granule mobilization.
    J Physiol. 1996 Jul 1;494 ( Pt 1):41-52 PMID: 8814605
  30. Multiple exocytotic pathways in pancreatic beta cells.
    J Cell Biol. 1997 Jul 14;138(1):55-64 PMID: 9214381
  31. Insulinotropic glucagon-like peptide-1-mediated activation of non-selective cation currents in insulinoma cells is mimicked by maitotoxin.
    J Biol Chem. 1997 Jul 18;272(29):17987-93 PMID: 9218425
  32. Protein kinase A-dependent and -independent stimulation of exocytosis by cAMP in mouse pancreatic B-cells.
    J Physiol. 1997 Jul 1;502 ( Pt 1):105-18 PMID: 9234200
  33. Rim is a putative Rab3 effector in regulating synaptic-vesicle fusion.
    Nature. 1997 Aug 7;388(6642):593-8 PMID: 9252191
  34. Multisite regulation of insulin secretion by cAMP-increasing agonists: evidence that glucagon-like peptide 1 and glucagon act via distinct receptors.
    Pflugers Arch. 1997 Sep;434(5):515-24 PMID: 9242714
  35. Intracellular cAMP potentiates voltage-dependent activation of L-type Ca2+ channels in rat islet beta-cells.
    Pflugers Arch. 1998 Mar;435(4):578-80 PMID: 9446708
  36. Cellular regulation of islet hormone secretion by the incretin hormone glucagon-like peptide 1.
    Pflugers Arch. 1998 Apr;435(5):583-94 PMID: 9479010
  37. Correlating structure and function in ATP-sensitive K+ channels.
    Trends Neurosci. 1998 Jul;21(7):288-94 PMID: 9683320
  38. Neurotransmitters and their receptors in the islets of Langerhans of the pancreas: what messages do acetylcholine, glutamate, and GABA transmit?
    Endocrine. 1998 Jun;8(3):213-23 PMID: 9741825
  39. Sulfonylureas enhance exocytosis from pancreatic beta-cells by a mechanism that does not involve direct activation of protein kinase C.
    Diabetes. 1998 Nov;47(11):1722-6 PMID: 9792541
  40. cAMP-GEFII is a direct target of cAMP in regulated exocytosis.
    Nat Cell Biol. 2000 Nov;2(11):805-11 PMID: 11056535
  41. Mechanisms of synaptic vesicle exocytosis.
    Annu Rev Cell Dev Biol. 2000;16:19-49 PMID: 11031229
  42. The stimulatory action of tolbutamide on Ca2+-dependent exocytosis in pancreatic beta cells is mediated by a 65-kDa mdr-like P-glycoprotein.
    Proc Natl Acad Sci U S A. 1999 May 11;96(10):5539-44 PMID: 10318919
  43. Priming of insulin granules for exocytosis by granular Cl(-) uptake and acidification.
    J Cell Sci. 2001 Jun;114(Pt 11):2145-54 PMID: 11493650
Article Info
Journal
The Journal of general physiology
Abbr.
J Gen Physiol
ISSN
0022-1295
DOI
10.1085/jgp.20028707
Published
2003-03-00
Pages
181-97
Language
English
Region
United States
NLM ID
2985110R
PMCID
PMC2217330
Subset
IM
Grants
NIDDK NIH HHS · R01 DK058508 · United States
NIDDK NIH HHS · DK58508 · United States
External Links
PubMed source DOI: 10.1085/jgp.20028707 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2