The effect of nitric oxide on glucose metabolism.
Nitric oxide (NO) is an important bioactive signaling molecule that mediates a variety of normal physiological functions, which, if altered, could contribute to the genesis of many pathological conditions, including diabetes. In this study, we examined the possible diabetogenicity of NO by noting differences in the cellular binding of insulin in dogs treated with the NO donor, S-nitrosoglutathione (GSNO) compared to captopril-treated controls. GSNO administration resulted in an abnormality in glucose metabolism which was attributed to decreased binding of insulin to its receptor on the cell membrane of mononuclear leucocytes, 11.60 +/- 0.60% in GSNO-treated dogs compared with 18.10 +/- 1.90% in captopril-treated control (p < 0.05). The decreased insulin binding was attributed to decreased insulin receptor sites per cell, 21.43 +/- 2.51 x 10(4) in GSNO-treated dogs compared with 26.60 +/- 1.57 x 10(4) in captopril-treated controls (p < 0.05). Average affinity analysis of the binding data demonstrated that this decrease in insulin binding was also due to a decrease in average affinity of the receptor on mononuclear leucocytes for insulin. This was evident by a decrease in empty and filled site affinities in GSNO-treated dogs compared with that of captopril-treated dogs (p < 0.05). It appears that GSNO is exerting its effect by decreasing the number of insulin receptor sites and/or decreasing the average receptor affinity. These results provide evidence for a novel role of NO as a modulator of insulin binding and the involvement of NO in the aetiology of diabetes mellitus.
Ragoobirsingh
Dalip
D
Department of Basic Medical Sciences, Biochemistry Section, University of the West Indies, Mona Campus, Jamaica. dalip.ragoobirsingh@uwimona.edu.jm
McGrowder
Donovan
D
Dasgupta
Tara
T
Brown
Paul
P
D000818:Animals; D001667:Binding, Competitive; D002216:Captopril / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000378:metabolism; D004285:Dogs; D005260:Female; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D011972:Receptor, Insulin / Q000378:metabolism; D026422:S-Nitrosoglutathione / Q000494:pharmacology
D007328:Insulin; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D002216:Captopril; D011972:Receptor, Insulin; D005947:Glucose