Structural specificity of nucleotides for insulin secretory action from the isolated perfused rat pancreas. 1979

M M Loubatieres-Mariani, and J Chapal, and F Lignon, and G Valette

The study concerned the effects of variuos nucleotides on the insulin secretion from the isolated perfused rat pancreas. ATP, the first nucleotide studied, increased the insulin release induced by glucose 1.5 g/l. There was a first immediate peak followed by a second significant and durable increase. The log dose-response curve was linear for concentrations ranging from 0.825 microM to 330 microM. The effects of natural adenine derivatives (ATP, ADP, 5' AMP, cAMP and adenosine) were compared. ATP was the most active compound; ADP had nearly the same activity as ATP (relative potency ATP/ADP = 3.2); 5' AMP, cAMP and adenosine displayed a very weak activity (about 100 fold less active). Adenylimido-diphosphate (AMP-PNP), a non-phosphorylating structural analogue of ATP, clearly stimulated insulin secretion and its effect was concentration-related. It was about 10 fold less active than ATP. The comparison of triphosphorylated derivatives from various purine nucleosides (ATP, GTP, ITP) or pyrimidine nucleosides (CTP and UTP) showed that only the purine derivatives had a strong insulin secretory effect with, in order of decreasing activity: ATP greater than GTP greater than ITP. These results show that certain structural features (purine basis and di- or triphosphate groups) are essential to elicit an insulin secretory effect.

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
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D009711 Nucleotides The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed) Nucleotide
D011685 Purine Nucleotides Purines attached to a RIBOSE and a phosphate that can polymerize to form DNA and RNA. Nucleotides, Purine
D011742 Pyrimidine Nucleotides Pyrimidines with a RIBOSE and phosphate attached that can polymerize to form DNA and RNA. Nucleotides, Pyrimidine
D000078790 Insulin Secretion Production and release of insulin from PANCREATIC BETA CELLS that primarily occurs in response to elevated BLOOD GLUCOSE levels. Secretion, Insulin
D000227 Adenine Nucleotides Adenine Nucleotide,Adenosine Phosphate,Adenosine Phosphates,Nucleotide, Adenine,Nucleotides, Adenine,Phosphate, Adenosine,Phosphates, Adenosine
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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