In:
IUBMB Life, Wiley, Vol. 49, No. 5 ( 2000-05), p. 441-450
Abstract:
Incubation of various tissues, including heart, liver, kidney, muscle, and intestine from mice and erythrocytes or their membrane fractions from humans, with physiologic concentration of insulin resulted in the activation of a membrane‐bound nitric oxide synthase (NOS). Activation of NOS and synthesis of NO were stimulated by the binding of insulin to specific receptors on the cell surface. A Lineweaver‐Burk plot of the enzymatic activity demonstrated that the stimulation of NOS by insulin was related to the decrease in the Km for L‐arginine, the substrate for NOS, with a simultaneous increase of Vmax. Addition of NG‐nitro‐L‐arginine methyl ester (LNAME), a competitive inhibitor of NOS, to the reaction mixture completely inhibited the hormone‐stimulated NO synthesis in all tissues. Furthermore, NO had an insulin‐like effect in stimulating glucose transport and glucose oxidation in muscle, a major site for insulin action. Addition of NAME to the reaction mixture completely blocked the stimulatory effect of insulin by inhibiting both NO production and glucose metabolism, without affecting the hormone‐stimulated tyrosine or phosphatidylinositol 3‐kinases of the membrane preparation. Injection of NO in alloxan‐induced diabetic mice mimicked the effect of insulin in the control of hyperglycemia (i.e., lowered the glucose content in plasma). However, injection of NAME before the administration of insulin to diabetic‐induced and nondiabetic mice inhibited not only the insulin‐stimulated increase of NO in plasma but also the glucose‐lowering effect of insulin.
Type of Medium:
Online Resource
ISSN:
1521-6543
,
1521-6551
DOI:
10.1080/152165400410308
Language:
English
Publisher:
Wiley
Publication Date:
2000
detail.hit.zdb_id:
2009952-6
detail.hit.zdb_id:
1492141-8
SSG:
12
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