Protective action by hemin against interleukin-1 beta induced inhibition of rat pancreatic islet function. 1994

N Welsh, and S Sandler
Department of Medical Cell Biology, Uppsala University, Sweden.

We have presently investigated the putative protective role of hemin against the inhibitory actions of the cytokine interleukin-1 beta (IL-1 beta) on isolated rat pancreatic islets. For this purpose, islets were isolated from adult rats, pre-cultured for 3-7 days in RPMI 1640 medium + 10% fetal calf serum and then exposed to IL-1 beta (5 ng/ml), hemin for 1, 7 or 24 h after which islet nitrite production, aconitase activity, glucose oxidation rates, glucose-stimulated insulin release and medium insulin accumulation were determined. It was found that hemin did not prevent IL-1 beta induced nitrite production. On the other hand, hemin partially counteracted the IL-1 beta induced decrease in aconitase activity, glucose oxidation, insulin release and medium insulin accumulation. This protective effect was present at a hemin concentration of 10 microM and most pronounced at 100 microM. Furthermore, hemin induced the synthesis of a 31 kDa protein, which was shown to be heme oxygenase as demonstrated by Western blot analysis. Finally, the protease inhibitor N-alpha-tosyl-L-lysine chloromethyl ketone (TLCK), which protects against IL-1 beta by decreasing nitric oxide production, was found to act additively in combination with hemin in alleviating the IL-1 beta effects. It is proposed that the beneficial effects of hemin against IL-1 beta could be related to scavenging of nitric oxide and/or an increased resistance to nitric oxide production.

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
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
D008297 Male Males
D009573 Nitrites Salts of nitrous acid or compounds containing the group NO2-. The inorganic nitrites of the type MNO2 (where M Nitrite
D010084 Oxidation-Reduction A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). Redox,Oxidation Reduction
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
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
D006419 Heme Oxygenase (Decyclizing) A mixed function oxidase enzyme which during hemoglobin catabolism catalyzes the degradation of heme to ferrous iron, carbon monoxide and biliverdin in the presence of molecular oxygen and reduced NADPH. The enzyme is induced by metals, particularly cobalt. Haem Oxygenase,Heme Oxygenase,Oxygenase, Haem,Oxygenase, Heme

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