Document Detail


Glucagon-like peptide-1 induces a cAMP-dependent increase of [Na+]i associated with insulin secretion in pancreatic beta-cells.
MedLine Citation:
PMID:  14534075     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glucagon-like peptide-1 (GLP-1) elevates the intracellular free calcium concentration ([Ca2+]i) and insulin secretion in a Na+-dependent manner. To investigate a possible role of Na ion in the action of GLP-1 on pancreatic islet cells, we measured the glucose-and GLP-1-induced intracellular Na+ concentration ([Na+]i), [Ca2+]i, and insulin secretion in hamster islet cells in various concentrations of Na+. The [Na+]i and [Ca2+]i were monitored in islet cells loaded with sodium-binding benzofuran isophthalate and fura 2, respectively. In the presence of 135 mM Na+ and 8 mM glucose, GLP-1 (10 nM) strongly increased the [Na+]i, [Ca2+]i, and insulin secretion. In the presence of 13.5 mM Na+, both glucose and GLP-1 increased neither the [Na+]i nor the [Ca2+]i. In a Na+-free medium, GLP-1 and glucose did not increase the [Na+]i. SQ-22536, an inhibitor of adenylate cyclase, and H-89, an inhibitor of PKA, incompletely inhibited the response. In the presence of both 8 mM glucose and H-89, 8-pCPT-2'-O-Me-cAMP, a PKA-independent cAMP analog, increased the insulin secretion and the [Na+]i. Therefore, we conclude that GLP-1 increases the cAMP level via activation of adenylate cyclase, which augments the membrane Na+ permeability through PKA-dependent and PKA-independent mechanisms, thereby increasing the [Ca2+]i and promoting insulin secretion from hamster islet cells.
Authors:
Yoshikazu Miura; Hisao Matsui
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  285     ISSN:  0193-1849     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2003-10-09     Completed Date:  2003-11-20     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E1001-9     Citation Subset:  IM    
Affiliation:
Department of Hygiene, Dokkyo University School of Medicine, 880 Mibu, Tochigi 321-0293, Japan. y-miura@dokkyomed.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Adenine / analogs & derivatives*,  pharmacology
Adenylate Cyclase / antagonists & inhibitors
Animals
Calcium / metabolism
Cricetinae
Cyclic AMP / analogs & derivatives*,  pharmacology*
Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
Enzyme Inhibitors / pharmacology
Gadolinium / pharmacology
Glucagon / pharmacology*
Glucagon-Like Peptide 1
Glucose / pharmacology
Insulin / secretion*
Islets of Langerhans / drug effects,  metabolism*,  secretion
Isoquinolines / pharmacology
Male
Mesocricetus
Ouabain / pharmacology
Peptide Fragments / pharmacology*
Protein Precursors / pharmacology*
Sodium / administration & dosage,  metabolism*
Somatostatin / pharmacology
Sulfonamides*
Tetrodotoxin / pharmacology
Chemical
Reg. No./Substance:
0/8-(4-chloro-phenylthio)-2'-O-methyladenosine-3'-5'-cyclic monophosphate; 0/Enzyme Inhibitors; 0/Isoquinolines; 0/Peptide Fragments; 0/Protein Precursors; 0/Sulfonamides; 11061-68-0/Insulin; 127243-85-0/H 89; 17318-31-9/9-(tetrahydro-2-furyl)-adenine; 4368-28-9/Tetrodotoxin; 50-99-7/Glucose; 51110-01-1/Somatostatin; 60-92-4/Cyclic AMP; 630-60-4/Ouabain; 73-24-5/Adenine; 7440-23-5/Sodium; 7440-54-2/Gadolinium; 7440-70-2/Calcium; 89750-14-1/Glucagon-Like Peptide 1; 9007-92-5/Glucagon; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases; EC 4.6.1.1/Adenylate Cyclase

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