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Glucagon-like peptide-1 induces a cAMP-dependent increase of [ Na ] i associated with insulin secretion in pancreatic-cells
| Content Provider | Semantic Scholar |
|---|---|
| Author | Miura, Yoshikazu Matsui, Hisao |
| Copyright Year | 2003 |
| Abstract | Miura, Yoshikazu, and Hisao Matsui. Glucagon-like peptide-1 induces a cAMP-dependent increase of [Na ]i associated with insulin secretion in pancreatic islet -cells. Am J Physiol Endocrinol Metab 285: E1001–E1009, 2003; 10.1152/ajpendo.00005.2003.—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 glucoseand 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-MecAMP, 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. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://ajpendo.physiology.org/content/ajpendo/285/5/E1001.full.pdf |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 8-chloro-cyclic adenosine monophosphate AM broadcasting Adenylate Cyclase Adenylyl Cyclase 9 Analog Benzofurans Calcium ion Fura-2 Glucagon Glucagon-Like Peptide 1 Glucose H 89 Iontophoresis Islets of Langerhans SQ 22536 Sodium Tissue membrane insulin secretion potassium-binding benzofuran-isophthalate acetoxymethyl ester |
| Content Type | Text |
| Resource Type | Article |
