Cyclic AMP, a Mediator of GLP-1, Acts in Concert with Glucose and Tolbutamide to Increase Cytosolic Ca2+ in Pancreatic B-Cells
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Cyclic AMP (cAMP) plays an important role in the regulation of islet B-cell function and stimulates insulin release in a glucose-dependent manner(1). Several physiologic peptides such as truncated glucagon-like peptide-1 (GLP-1), gastric inhibitory peptide (GIP) and glucagon are known to elevate cAMP level in islets and stimulate insulin release also in a glucose-dependent manner(1–4). It has been recently shown that both a rise in cAMP and these peptides increase the cytosolic free Ca2+ concentration ([Ca2+]i) in pancreatic B-cells(3–7), the key intracellular signal that triggers exocytosis of insulin(8,9). The increase in [Ca2+]i is also glucose-dependent(6) and is tightly linked to insulin release(3). However, the mechanisms for the glucose-dependent action of cAMP to increase [Ca2+]i is not well understood. Whether cAMP increases [Ca2+]i via specific cooperation with glucose, a fuel secretagogue, or also with other types of insulin secretagogues is of particular importance. Whether the glucose-dependent action of the peptides to increase [Ca2+]i is mediated by a rise in cAMP is not thoroughly determined.
KeywordsInsulin Release Pituitary Adenylate Cyclase Activate Polypeptide Gastric Inhibitory Polypeptide Stimulate Insulin Release Krebs Ringer Bicarbonate Buffer
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