Effect of metformin on nitric oxide synthase in genetically obese (ob/ob) mice

被引:27
作者
Kumar, VB
Bernardo, AE
Vyas, K
Franko, M
Farr, S
Lakshmanan, L
Buddhiraju, C
Morley, JE
机构
[1] St Louis VA Med Ctr, Ctr Geriatr Res Educ & Clin, St Louis, MO 63125 USA
[2] St Louis Univ, Hlth Sci Ctr, St Louis, MO 63104 USA
关键词
metformin; nitric oxide synthase; thin layer chromatography (TLC); NOS inhibition; obese;
D O I
10.1016/S0024-3205(01)01359-5
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Genetically obese (ob/ob) mice were employed for the study of the effect of metformin on activity and expression of nitric oxide synthase (NOS) in vitro and in vivo. For in vitro analysis, mouse liver extracts were used. For the in vivo study, (ob/ob) and their control litter mates (ob/c) mice were injected with specified amounts of metformin and the expression of NOS in the adipose tissue and hypothalamus was measured by Western blotting. Results show that metformin exhibited a biphasic effect on NOS activity in vitro. Expression of metformin was differentially altered in the hypothalamus and adipose tissues of the normal and ob/ob animals that were treated with metformin. Further, a significant decrease in food intake occurred in the (ob/ob) mice that received metformin. This decrease in food intake was not accompanied by changes in serum glucose. At inhibitory concentrations, hypothalamic NOS expression changes differentially in normal and ob/ob mice. In normal mice, metformin stimulated NOS expression, while in ob/ob mice there was an inhibition. NOS expression increased in brown adipose tissue of metformin treated control mice, while no such increase was observed in ob/ob mice. No effect of metformin was observed in white adipose tissue of control or obese mice. Thus, metformin may produce anorectic effects through modulation of NOS. (C) 2001 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:2789 / 2799
页数:11
相关论文
共 41 条
[31]   The effect of metformin on liver blood flow in vivo in normal subjects and patients with non insulin dependent diabetes [J].
Signore, A ;
Fiore, V ;
Chianelli, M ;
Procaccini, E ;
Barone, R ;
Ronga, G ;
Negri, M ;
Pozzilli, P .
DIABETES RESEARCH AND CLINICAL PRACTICE, 1996, 33 (02) :83-87
[32]  
SIGNORE A, 1995, DIABETES METAOBLISM, V1, pS13
[33]   REEVALUATION OF A BIGUANIDE, METFORMIN - MECHANISM OF ACTION AND TOLERABILITY [J].
SIRTORI, CR ;
PASIK, C .
PHARMACOLOGICAL RESEARCH, 1994, 30 (03) :187-228
[34]   METFORMIN IMPROVES PERIPHERAL VASCULAR FLOW IN NONHYPERLIPIDEMIC PATIENTS WITH ARTERIAL-DISEASE [J].
SIRTORI, CR ;
FRANCESCHINI, G ;
GIANFRANCESCHI, G ;
SIRTORI, M ;
MONTANARI, G ;
BOSISIO, E ;
MANTERO, E ;
BONDIOLI, A .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1984, 6 (05) :914-923
[35]   Selective pharmacological inhibition of distinct nitric oxide synthase isoforms [J].
Southan, GJ ;
Szabo, C .
BIOCHEMICAL PHARMACOLOGY, 1996, 51 (04) :383-394
[36]  
TNAKUMARI L, 1996, NEUROSCI LETT, V215, P153
[37]   United Kingdom prospective diabetes study 17: A 9-year update of a randomized, controlled trial on the effect of improved metabolic control on complications in non-insulin-dependent diabetes mellitus [J].
Turner, R ;
Cull, C ;
Holman, R .
ANNALS OF INTERNAL MEDICINE, 1996, 124 (01) :136-145
[38]  
Wang Y, 1997, J BIOL CHEM, V272, P11392
[39]  
Waterborg J H, 1994, Methods Mol Biol, V32, P1
[40]   Inactivation of nitric oxide synthase isoforms by diaminoguanidine and N-G-amino-L-arginine [J].
Wolff, DJ ;
Lubeskie, A .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1996, 325 (02) :227-234