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Acta Physiologica 2012; Volume 206, Supplement 693
Joint FEPS and Spanish Physiological Society Scientific Congress 2012
9/8/2012-9/11/2012
Santiago de Compostela, Spain
IMPACT OF NITRIC OXIDE SYNTHASE (NOS) ACTIVITY ON INSULIN CLEARANCE
Abstract number: P146
Martins1 F. O., Jones2 J. G., Ribeiro3 R., Mari4 A., Natali5 A., Macedo6 M. P.
1Centre for Neurosciences and Cell Biology, University of Coimbra; Centro de Estudos de Doenas Crnicas, New University of Lisbon, Centre for Neurosciences and Cell Biology, University of Coimbra; Centro de Estudos de Doenas Crnicas, New Universi
2Centre for Neurosciences and Cell Biology, University of Coimbra; Portuguese Diabetes Association (APDP-ERC), Lisbon, Portugal, Centre for Neurosciences and Cell Biology, University of Coimbra; Portuguese Diabetes Association (APDP-ERC), Lisbon
3Centro de Estudos de Doenas Crnicas, New University of Lisbon; Portuguese Diabetes Association (APDP-ERC), Lisbon, Portugal, Centro de Estudos de Doenas Crnicas, New University of Lisbon; Portuguese Diabetes Association (APDP-ERC), Lisbon, Port
4Institute of Biomedical Engineering, CNR, Padova, Institute of Biomedical Engineering, CNR, Padova,
5Centro de Estudos de Doenas Crnicas, New University of Lisbon; Metabolism Unit, Department of Internal Medicine, University of Pisa, Italy , Centro de Estudos de Doenas Crnicas, New University of Lisbon; Metabolism Unit, Department of Internal
6Centro de Estudos de Doenas Crnicas, New University of Lisbon; Portuguese Diabetes Association (APDP-ERC), Lisbon, Centro de Estudos de Doenas Crnicas, New University of Lisbon; Portuguese Diabetes Association (APDP-ERC), Lisbon
Objectives:
Impairment of insulin clearance (IC) may be a major factor in the development of hyperinsulinemia in conditions such as insulin resistance and obesity. While the role of NOS in the regulation of peripheral insulin sensitivity is well established, its role in IC and β-cell sensitivity modulation is not clear. Herein, we tested the hypothesis that increased NOS activity decreases both β-cell sensitivity as well as hepatic IC mediated via inhibition of insulin degrading enzyme (IDE).
Materials:
In this study, 12 weeks male Wistar rats were divided in two groups: NOS acutely inhibited [L-nitroarginine methyl ester (L-NAME); 35 ug/kg/min; i.v.] and NOS chronically inhibited (L-NAME 10 mg/kg; daily; 4 weeks; s.c.). Each animal was submitted to an intra-enteric glucose tolerance test (IEGTT) and plasma insulin and c-peptide levels were analyzed. Hepatic IDE activity was measured and total IC was quantified from the ratio of plasma c-peptide and insulin levels. β-cell sensitivity was obtained from the average slope of c-peptide plotted against plasma glucose levels.
Results:
Both L-NAME treatments promoted an increase in total IC (AUC: Control: 78237 ± 3283; Acute L-NAME: 128278 ± 7954, p<0,001; Chronic L-NAME: 103445 ± 4344, p<0,05) which was associated with an increase in hepatic IDE activity (RFUs/mg protein: Control: 6,7 ± 1,5; Acute L-NAME: 11,3 ± 1,4, p<0,05; Chronic L-NAME: 10,6 ± 0,6, p<0,05). β-cell sensitivity significantly increased with both acute and chronic L-NAME treatment (slope: Control: 17,0 ± 2,602; Acute L-NAME: 29,2 ± 2,3, p<0,05; Chronic L-NAME 10: 24,1 ± 3,0, p<0,05).
Conclusions:
In conclusion, our results support the hypothesis that concurrent with suppression of -cell insulin secretion by pancreatic NO, NO derived from constitutive NOS also inhibits hepatic IDE activity and consequently IC to achieve optimal plasma insulin levels.
Supported by: SFRH/BD/51194/2010 and PIC/IC/82956/2007, FCT, Portugal;
To cite this abstract, please use the following information:
Acta Physiologica 2012; Volume 206, Supplement 693 :P146