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Insulin sensitivity in vivo is enhanced by systemic administration of S-nitrosothiols but not by SIN-1 in wistar rats
Insulin resistance has been associated both with impaired nitric oxide (NO) action and decreased glutathione (GSH) levels (Guarino et al. 2003). GSH and NO react promptly to form S-nitrosoglutathione, (GSNO) ( Schrammel et al. 1998) , which suggests that NO insulin-sensitizing effect involves the formation of a nitrosothiol intermediate. We tested the hypothesis that intravenous administration of the nitrosothiols GSNO or S-nitrosoacetylpennicilamine (SNAP) increases total insulin sensitivity, when compared to a non-nitrosothiol NO-donor (3-morpholinosydnonimine, SIN-1) 24-h fasted male Wistar rats (250-300g) were anesthetized with sodium pentobarbital (65mg/Kg). Two nitrosothiols, GSNO (15mg/kg) and SNAP (10 mg/kg), and a NO-donor SIN-1 (10.0 mg/kg), were perfused intravenously at equimolar doses. A modified euglycemic clamp was used to quantitate insulin sensitivity in the fasted state and after drug administration (50mU/kg insulin). Insulin sensitivity was not significantly altered by administration of SIN-1 (from 93.5±10.4 to 88.7±6.9 mg glucose/kg bw, n=5). In contrast, intravenous infusion of both nitrosothiols significantly increased insulin sensitivity from 115.5±9.7to170.8±21.1 mg glucose/kg bw (p< 0.001, paired t-test, n= 8) after GSNO administration and from 76.4±10.2 to 187.0±25.1 mg glucose/kg bw after SNAP administration (p<0.005, paired t-test, n=6). Our results support the hypothesis that nitrosothiols increase insulin sensitivity in contrast with non-nitrosothiol NO-donors.
Guarino MP, Afonso RA, Raimundo N, Raposo JF, Macedo MP. (2003) Am J Physiol Gastrointest Liver Physio l. 284(4): G588. This study was supported by FCT grant POCTI/NSE/42397/2001 and by APDP. Maria P. Guarino was supported by a FCT fellowship BD/4916/2001. |
