Biomaterial Database

Inhibition of phosphodiesterase 3B in insulin-secreting cells of normal and streptozocin-nicotinamide-induced diabetic rats: implications for insulin secretion. 2014

A Zywert, and K Szkudelska, and T Szkudelski

Department of Animal Physiology and Biochemistry, Poznan University of Life Sciences, Poznan, Poland. tszkudel@jay.up.poznan.pl.

Cyclic adenosine monophosphate (cAMP) plays important role in the potentiation of insulin secretion in pancreatic B-cells. However, the relevance of cAMP-degrading enzymes in the regulation of insulin secretion is not fully elucidated. The present work was undertaken to determine effects of inhibition of phosphodiesterase 3B (PDE3B) by amrinone on insulin secretion from pancreatic islets and perfused pancreas of normal and mildly diabetic rats. Inhibition of this enzyme was demonstrated to substantially increase insulin-secretory response to 6.7 mM glucose in the isolated islets and perfused pancreas of non-diabetic rats. Increment in glucose-induced insulin secretion resulting from inhibition of PDE3B was accompanied by an increase in islet cAMP levels and was suppressed by inhibition of protein kinase A. It was also demonstrated that insulin secretion stimulated by glucose and 1 μM forskolin was only slightly elevated in the presence of amrinone. Moreover, insulin release induced by succinate instead of glucose was also augmented by inhibition of PDE3B in rat islets. However, exposure of the pancreatic islets of streptozotocin-nicotinamide-induced diabetic rats to amrinone appeared to be without any effect on glucose-induced insulin secretion. Similar lack of response was shown in the perfused pancreas of diabetic rats. These results indicate that inhibition of PDE3B by amrinone significantly augments insulinotropic action of physiological glucose in B-cells of normal rats. This effect is mediated via protein kinase A and may be also induced in the presence of metabolizable stimuli other than glucose. Effects generated by amrinone were demonstrated to be, however, insufficient to enhance glucose-induced insulin secretion in B-cells of streptozotocin-nicotinamide-induced diabetic rats.

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
D008297	Male		Males
D009536	Niacinamide	An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and PELLAGRA. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake.	Nicotinamide,Vitamin B 3,Vitamin PP,3-Pyridinecarboxamide,Enduramide,Nicobion,Nicotinsäureamid Jenapharm,Papulex,Vitamin B3,3 Pyridinecarboxamide,B 3, Vitamin,B3, Vitamin,Jenapharm, Nicotinsäureamid
D010726	Phosphodiesterase Inhibitors	Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.	Phosphodiesterase Antagonists,Phosphodiesterase Inhibitor,Phosphoric Diester Hydrolase Inhibitors,Antiphosphodiesterases,Inhibitor, Phosphodiesterase
D003921	Diabetes Mellitus, Experimental	Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY.	Alloxan Diabetes,Streptozocin Diabetes,Streptozotocin Diabetes,Experimental Diabetes Mellitus,Diabete, Streptozocin,Diabetes, Alloxan,Diabetes, Streptozocin,Diabetes, Streptozotocin,Streptozocin Diabete
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
D000078790	Insulin Secretion	Production and release of insulin from PANCREATIC BETA CELLS that primarily occurs in response to elevated BLOOD GLUCOSE levels.	Secretion, Insulin
D000676	Amrinone	A positive inotropic cardiotonic (CARDIOTONIC AGENTS) with vasodilator properties, phosphodiesterase 3 inhibitory activity, and the ability to stimulate calcium ion influx into the cardiac cell.	5-Amino-(3,4'-bipyridine)-6(1H)-one,Amrinon,Cordemcura,Inocor,Win-40680,Wincoram,Win 40680,Win40680
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