Cysteine is a key mediator in the increment of insulin sensitivity over a glucose tolerance test
Presentation Number: MON-856
Date of Presentation: June 17th, 2013
Joana Margarida Gaspar*, Ricardo Alexandre Afonso, Fátima Oliveira Martins, Inês Couto Coelho and Maria Paula Macedo
Faculdade Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal
The increase in peripheral insulin action after a meal, known as meal-induced insulin sensitization (MIS) is a mechanism that contributes to the regulation of postprandial glucose homeostasis. We have described that peripheral postprandial glucose disposal requires the presence of glucose and amino acids in the intestine to trigger the MIS, which is abolished in the absence of hepatic parasympathetic function. However, it remains unknown which specific amino acids are involved in MIS activation.
Since cysteine is a semi-essential amino acid and a substrate for glutathione synthesis, which is essential in postprandial glucose homeostasis, we tested the hypothesis that cysteine is an essential feeding signal to trigger the MIS mechanism.
Female Wistar rats with 9-weeks old were used. After 24h fast the animals were anesthetized and submitted to surgery involving enteric cannulation. N-acetyl-cysteine (NAC, 1mmol/kg; 15ml/h) was administered intra-enterically, as a source of cysteine. Immediately afterwards, an intra-enteric glucose tolerance test (IEGTT) was performed. Insulin sensitivity was also assessed both in the fasted state and 120 min after glucose administration (10 ml/kg, 60 ml/h) using a modified euglycemic clamp. In a separate set of experiments, hepatic parasympathetic denervation was performed during surgery and then NAC and glucose were administered. Blood samples were collected to assess glucose, insulin and C-peptide plasma levels.
NAC administration did not alter plasma glucose excursions throughout the IEGTT, suggesting that NAC does not affect glucose tolerance. Fasting insulin sensitivity (128.6±11.2 mg/kg) was not different from post-NAC (105.8±3.4 mg/kg) and post-glucose (117.5±12.2 mg/kg) insulin sensitivity. However, insulin sensitivity was significantly higher after administration of NAC with glucose, (227.3±17.8 mg/kg), suggesting that NAC and glucose together can trigger the MIS. When parasympathetic denervation was done, insulin sensitivity obtained after NAC+glucose was similar to that in the fasting state (129.3±14.7 mg/kg), suggesting that hepatic parasympathetic denervation prevents the MIS. The NAC+glucose group presented significantly lower plasma insulin levels, due to an increment in insulin clearance.
In conclusion, cysteine is an important amino acid, which function as a feeding signal and requires activation of hepatic parasympathetic nerves to induce MIS, contributing to the potentiation of postprandial insulin action.
Nothing to Disclose: JMG, RAA, FOM, ICC, MPM