Biomaterial Database

Insulin secretion. Interrelationships of glucose, cyclic adenosine 3:5-monophosphate, and calcium. 1975

M A Charles, and J Lawecki, and R Pictet, and G M Grodsky

Glucose elevates both cyclic adenosine 3:5-monophosphate (cyclic AMP) and insulin secretion rapidly and in a parallel dose-dependent fashion in perifused rat islets. Theophylline stimulates cyclic AMP much more than glucose, yet secretion is much less. When the two agents are combined, cyclic AMP is similar to theophylline alone yet secretion is augmented synergistically. Glucose-induced cyclic AMP generation and insulin secretion are dependent on extracellular calcium. Theophylline-induced insulin secretion is also extracellular calcium-dependent; however, theophylline-induced cyclic AMP elevation is independent of extracellular calcium. Thus, extracellular calcium has multiple effects on insulin secretion, some of which appear unrelated to a terminal secretory process. When glucose is combined with theophylline at physiologic levels of extracellular calcium, both the first and second phases of secretion are prominent. At extracellular calcium levels of 0.05 mM, only the second phase is prominent whereas at 10 nM extracellular calcium (ethylene glycol bis(beta-aminoethyl ether)-N,-tetraacetic acid) only the first phase is prominent. A divalent cation ionophore (a23187, Eli Lilly), which transports calcium and magnesium ions across biological membranes, was used to elucidate further the role of calcium and magnesium. If the ionophore (10 muM) is perifused for 5 min at low extracellular calcium and magnesium, and physiologic calcium is then added, a sudden spike of insulin release occurs in the absence of cyclic AMP generation. Similar results were obtained with magnesium. When the ionophore is perifused for 30 min at low calcium and magnesium, insulin secretion again occurs in the absence of cyclic AMP generation. Electron microscopic examination of the B cells following perifusion with the ionophore shows no specific alterations. These observations suggest that: (a) glucose elevates cyclic AMP, but the latter acts primarily as a positive feed-forward modulator of glucose-induced insulin release; and (b) extracellular calcium has multiple effects on insulin secretion both upon, and independent of, the cyclic AMP system.

UI	MeSH Term	Description	Entries
D007328	Insulin	A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).	Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007515	Islets of Langerhans	Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN.	Islands of Langerhans,Islet Cells,Nesidioblasts,Pancreas, Endocrine,Pancreatic Islets,Cell, Islet,Cells, Islet,Endocrine Pancreas,Islet Cell,Islet, Pancreatic,Islets, Pancreatic,Langerhans Islands,Langerhans Islets,Nesidioblast,Pancreatic Islet
D008854	Microscopy, Electron	Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.	Electron Microscopy
D010477	Perfusion	Treatment process involving the injection of fluid into an organ or tissue.	Perfusions
D011863	Radioimmunoassay	Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation.	Radioimmunoassays
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002852	Chromatography, Ion Exchange	Separation technique in which the stationary phase consists of ion exchange resins. The resins contain loosely held small ions that easily exchange places with other small ions of like charge present in solutions washed over the resins.	Chromatography, Ion-Exchange,Ion-Exchange Chromatography,Chromatographies, Ion Exchange,Chromatographies, Ion-Exchange,Ion Exchange Chromatographies,Ion Exchange Chromatography,Ion-Exchange Chromatographies
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005947	Glucose	A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.	Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D000001	Calcimycin	An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.	4-Benzoxazolecarboxylic acid, 5-(methylamino)-2-((3,9,11-trimethyl-8-(1-methyl-2-oxo-2-(1H-pyrrol-2-yl)ethyl)-1,7-dioxaspiro(5.5)undec-2-yl)methyl)-, (6S-(6alpha(2S,3S),8beta(R*),9beta,11alpha))-,A-23187,A23187,Antibiotic A23187,A 23187,A23187, Antibiotic