Modulation by cytosolic pH of calcium and rubidium fluxes in rat pancreatic islets. 1988

L Best, and A P Yates, and C Gordon, and S Tomlinson
Department of Medicine, University of Manchester, U.K.

Cytosolic pH (pHi) of pancreatic islet cells was assessed using the fluorescent dye 2'7'-biscarboxyethyl-5'(6')-carboxyfluorescein (BCECF). pHi was rapidly lowered by addition of the sodium salt of a weak acid or by treatment with amiloride. In the latter case, no recovery of pHi occurred. NH4Cl produced a rise in pHi. Stimulation of islet cells with glyceraldehyde produced a sustained fall in pHi, whereas glucose and alpha-ketoisocaproate caused a small, gradual rise in pHi. Intracellular acidification, particularly with amiloride, resulted in an immediate potentiation of glucose-induced insulin secretion from perifused islets. In the case of weak acid treatment, subsequent removal of the weak acid produced a paradoxical stimulation of insulin release which was not observed upon removal of amiloride. NH4Cl produced a transient stimulation followed by a reduction in the rate of glucose-induced insulin secretion. A reduction in pHi, either in response to weak acid or amiloride treatment, was associated with a diminution in the rate of efflux of 86Rb+ and of 45Ca2+. Removal of weak acid produced a marked "rebound" stimulation of 86Rb+ and 45Ca2+ efflux. Treatment of islets with NH4Cl, either in the presence or absence of glucose or Ca2+, resulted in a marked stimulation of efflux of 86Rb+ and 45Ca2+. The stimulatory effect of NH4Cl on 45Ca2+ efflux was markedly impaired in the absence of Na+. It is concluded that pHi can influence the secretory activity of pancreatic islets, possibly via effects on potassium permeability and sodium-calcium exchange across the plasma membrane, resulting in altered mobilisation of calcium in the islet cell. However, it is unlikely that glucose or other nutrient stimuli activate islets solely via an effect on pHi.

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
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
D002463 Cell Membrane Permeability A quality of cell membranes which permits the passage of solvents and solutes into and out of cells. Permeability, Cell Membrane
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
D006863 Hydrogen-Ion Concentration The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D000078790 Insulin Secretion Production and release of insulin from PANCREATIC BETA CELLS that primarily occurs in response to elevated BLOOD GLUCOSE levels. Secretion, Insulin
D000584 Amiloride A pyrazine compound inhibiting SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with DIURETICS to spare POTASSIUM loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705) Amidal,Amiduret Trom,Amiloberag,Amiloride Hydrochloride,Amiloride Hydrochloride, Anhydrous,Kaluril,Midamor,Midoride,Modamide,Anhydrous Amiloride Hydrochloride,Hydrochloride, Amiloride,Hydrochloride, Anhydrous Amiloride,Trom, Amiduret
D000643 Ammonium Chloride An acidifying agent that has expectorant and diuretic effects. Also used in etching and batteries and as a flux in electroplating. Sal Ammoniac,Ammoniac, Sal,Chloride, Ammonium
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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