Regulation of 86Rb outflow from pancreatic islets: the dual effect of nutrient secretagogues. 1981

A R Carpinelli, and W J Malaisse

1. An increase in the concentration of extracellular D-glucose from zero to 1.7 mM or more (up to 16.7 mM) causes a rapid and sustained decrease in 86Rb fractional outflow rate (FOR) from prelabelled and perifused pancreatic rat islets. The 86Rb FOR also decreases when the concentration of D-glucose is raised from 1.7 mM or more (up to 5.6 mM) to higher values not exceeding 8.3 mM. 2. However, when the glucose concentration is raised from 8.3 mM (or 11.1 mM) to higher values, no decrease in 86Rb FOR is observed and, instead, a transient increase in 86Rb FOR now takes place. 3. Such a dual effect on 86Rb FOR is also observed when alpha-ketoisocaproic acid is used as the nutrient secretagogue or when the latter keto acid is used in combination with D-glucose. 4. The transient increase in 86Rb FOR evoked by D-glucose in islets already exposed to alpha-ketoisocaproate is abolished by mannoheptulose, suggesting that it depends on the integrity of glucose metabolism. 5. The transient increase in 86Rb FOR evoked, under suitable experimental conditions, by D-glucose of alpha-ketoisocaproate is abolished in the absence of extracellular Ca2+ and mimicked by theophylline and tolbutamide, suggesting that it is attributable to an increase in cytosolic Ca2+ concentration. The latter view is supported by the fact that the increase in 86Rb FOR coincides with an increase in 45Ca FOR, provided that Ca2+ is not removed from the extracellular medium. 6. It is concluded that, in contrast to the situation found when the concentration of the nutrient secretagogue is increased from a non-insulinotropic to a higher value, the stimulation of Ca2+ entry into islet cells and the subsequent increase in insulin secretion evoked by D-glucose or alpha-ketoisocaproate when the concentration of these nutrients is increased from intermediate (8.3-10.0 mM) to higher values is not attributable to a decrease in K+ conductance.

UI MeSH Term Description Entries
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
D007651 Keto Acids Carboxylic acids that contain a KETONE group. Oxo Acids,Oxoacids,Acids, Keto,Acids, Oxo
D011188 Potassium An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
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
D002208 Caproates Derivatives of caproic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain a carboxy terminated six carbon aliphatic structure. Hexanoates,Caproic Acid Derivatives,Caproic Acids,Hexanoic Acid Derivatives,Hexanoic Acids,Acid Derivatives, Caproic,Acid Derivatives, Hexanoic,Acids, Caproic,Acids, Hexanoic,Derivatives, Caproic Acid,Derivatives, Hexanoic Acid
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
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
D012413 Rubidium An element that is an alkali metal. It has an atomic symbol Rb, atomic number 37, and atomic weight 85.47. It is used as a chemical reagent and in the manufacture of photoelectric cells.
D012636 Secretory Rate The amount of a substance secreted by cells or by a specific organ or organism over a given period of time; usually applies to those substances which are formed by glandular tissues and are released by them into biological fluids, e.g., secretory rate of corticosteroids by the adrenal cortex, secretory rate of gastric acid by the gastric mucosa. Rate, Secretory,Rates, Secretory,Secretory Rates

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