Insulin sensitivity is dependent on a HISS (hepatic in- sulin sensitizing substance)-dependent component and on a HISS-independent component [1].
Proc. West. Pharmacol. Soc. 44: 25-26 (2001)
Nitric Oxide Synthase Inhibition Decreases Output of Hepatic Insulin Sensitizing Substance (HISS), which is Reversed by SIN-1 but not by Nitroprusside MARIA PEDRO GUARINO1,4, NINA CRUZ CORREIA1,2,4, JOÃO RAPOSO3 & MARIA PAULA MACEDO1,2,4* 1
Departamento de Fisiologia - FCM-UNL, Campo Mártires da Pátria, 130, 1169-056 Lisboa, Portugal; 2Instituto Superior de Ciências da SaúdeSul, Quinta da Granja, 2825 Monte da Caparica, Portugal; 3Instituto Português de Oncologia, Serviço de Endocrinologia, Rua Professor Lima Basto, 1093 Lisboa, Portugal; 4Associação Protectora dos Diabéticos de Portugal, Rua do Salitre, 118, Lisboa, Portugal
Insulin sensitivity is dependent on a HISS (hepatic insulin sensitizing substance)-dependent component and on a HISS-independent component [1]. HISS sensitizes skeletal muscle to insulin. Its release is dependent on the activation of hepatic muscarinic receptors. Moreover, nitric oxide (NO) produced in the liver is a key regulator of HISS release [2]. We studied the ability of different NO donors to reverse HISS-dependent insulin resistance. Two NO donors with distinct chemistries were used: 3morpholinosydnonimine (SIN-1, 5.0 mg/kg), which acts by releasing both NO and superoxide (O2-.) leading to the formation of the thionitrite, S-nitrosoglutathione (GSNO), in the presence of glutathione (GSH) [3]; and sodium nitroprusside (SNP, 20 nmol/kg/min), which releases NO promptly and whose activity is independent of the formation of nitrosothiols [4].
300
CONTROL
RIST INDEX (m g/Kg)
L-NAME 1mg/Kg IPV SNP 20nmol/Kg/min IPV
*
200
100
0
Figure 1. Intraportal administration of L-NAME (1mg/kg) significantly reduced (p
