Biomaterial Database

Rat pancreatic islet and RINm5F cell responses to epiandrosterone, dehydroepiandrosterone and interleukin-1 beta. 1998

S G Laychock

Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo 14214, USA. slaychoc@ubmed.buffalo.edu

Epiandrosterone (EA), dehydroepiandrosterone (DHEA), and their sulfate (-S) and acetate (-A) conjugates were investigated for effects on isolated pancreatic islets and RINm5F insulinoma cells. Interleukin-1 beta (IL-1 beta) inhibited glucose-stimulated insulin release in cultured islets, but the presence of EA, EA-A, and to a lesser extent EA-S, preserved the secretory response. IL-1 beta also increased islet nitrite production, which was antagonized by EA and EA-A, but not by EA-S. EA, EA-A, DHEA, and DHEA-A, but not EA-S and DHEA-S inhibited glucose-stimulated insulin release from islets. This response may be related to the inhibition of glucose transport by EA, EA-A, DHEA, DHEA-A, and DHEA-S, as observed in RINm5F cells. EA, EA-A, DHEA, and DHEA-A also inhibited glucose metabolism in RINm5F cells, whereas EA-S and DHEA-S had no effect. EA, EA-A, DHEA, and DHEA-A, but not the sulfate conjugates, also inhibited RINm5F cell IL-1 beta-induced nitric oxide synthase (iNOS) activity. IL-1 beta also increased cytosolic Cu/Zn-superoxide dismutase (SOD) and mitochondrial Mn-SOD in RINm5F cells. EA inhibited RINm5F cell Cu/Zn-SOD in the presence and absence of IL-1 beta, whereas EA-S increased basal enzyme activity and did not affect the IL-1 beta response. EA did not affect basal Mn-SOD activity and inhibited IL-1 beta-stimulated activity, whereas EA-S was without effect. IL-1 beta had no effect on catalase activity in RINm5F cells, whereas EA, EA-A, and DHEA-A inhibited catalase activity. Thus, EA and DHEA and their acetate congeners protected the beta-cell from the inhibitory effects of IL-1 beta, and inhibited glucose transport and oxidation, and inducible nitricoxide synthase expression. EA and DHEA also had profound effects on Cu/Zn-SOD, which may alter the toxic effects of hydrogen peroxide generation in beta-cells.

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
D007340	Insulinoma	A benign tumor of the PANCREATIC BETA CELLS. Insulinoma secretes excess INSULIN resulting in HYPOGLYCEMIA.	Adenoma, beta-Cell,Insuloma,beta-Cell Tumor,Adenoma, beta Cell,Adenomas, beta-Cell,Insulinomas,Insulomas,Tumor, beta-Cell,Tumors, beta-Cell,beta Cell Tumor,beta-Cell Adenoma,beta-Cell Adenomas,beta-Cell Tumors
D007375	Interleukin-1	A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.	IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
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
D009569	Nitric Oxide	A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.	Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D009573	Nitrites	Salts of nitrous acid or compounds containing the group NO2-. The inorganic nitrites of the type MNO2 (where M	Nitrite
D010190	Pancreatic Neoplasms	Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).	Cancer of Pancreas,Pancreatic Cancer,Cancer of the Pancreas,Neoplasms, Pancreatic,Pancreas Cancer,Pancreas Neoplasms,Pancreatic Acinar Carcinoma,Pancreatic Carcinoma,Acinar Carcinoma, Pancreatic,Acinar Carcinomas, Pancreatic,Cancer, Pancreas,Cancer, Pancreatic,Cancers, Pancreas,Cancers, Pancreatic,Carcinoma, Pancreatic,Carcinoma, Pancreatic Acinar,Carcinomas, Pancreatic,Carcinomas, Pancreatic Acinar,Neoplasm, Pancreas,Neoplasm, Pancreatic,Neoplasms, Pancreas,Pancreas Cancers,Pancreas Neoplasm,Pancreatic Acinar Carcinomas,Pancreatic Cancers,Pancreatic Carcinomas,Pancreatic Neoplasm
D002374	Catalase	An oxidoreductase that catalyzes the conversion of HYDROGEN PEROXIDE to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in ACATALASIA.	Catalase A,Catalase T,Manganese Catalase,Mn Catalase