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题名:Systemic inhibition of nitric oxide synthesis in non-diabetic individuals produces a significant deterioration in glucose tolerance by increasing insulin clearance and inhibiting insulin secretion.
作者:NATALI A; RIBEIRO R; BALDI S; TULIPANI A; ROSSI M; VENTURI E; MARI A; MACEDO MP; FERRANNINI E;
来源:Diabetologia. 2013 May;56(5):1183-91. doi: 10.1007/s00125-013-2836-x. Epub 2013 [ IF= 6.81 ] ]
URL :10.1007/s00125-013-2836-x
日期:20130606
摘要:AIMS/HYPOTHESIS: Endogenous NO inhibits insulin release in isolated beta cells
and insulin-degrading enzyme activity in hepatocytes, while NO release from
endothelial cells has been suggested to enhance insulin action. We assessed the
overall effect of systemic inhibition of endogenous NO synthesis on glucose
homeostasis in humans. METHODS: Twenty-four non-diabetic volunteers underwent two
hyperglycaemic (+7 mmol/l) clamps with either saline or L-NG-nitroarginine methyl
ester (L-NAME, at rates of 2.5, 5, 10 and 20 mug min(-1) kg(-1)) infusion.
Another five volunteers underwent an OGTT with either saline or L-NAME (20 mug
min(-1) kg(-1)) infusion. Blood pressure and heart rate were measured to monitor
NO blockade; during the OGTT, endothelial function was assessed by peripheral
arterial tonometry and insulin secretion by C-peptide deconvolution and insulin
secretion modelling. RESULTS: Compared with saline, L-NAME at the highest dose
raised mean blood pressure (+20 +/- 2 mmHg), depressed heart rate (-12 +/- 2 bpm)
and increased insulin clearance (+50%). First-phase insulin secretion was
impaired, but insulin sensitivity (M/I index) was unchanged. During the OGTT,
L-NAME raised 2 h plasma glucose by 1.8 mmol/l (p < 0.01), doubled insulin
clearance and impaired beta cell glucose sensitivity while depressing endothelial
function. CONCLUSIONS/INTERPRETATION: In humans, systemic NO blockade titrated to
increase blood pressure and induce endothelial dysfunction does not affect
insulin action but significantly impairs glucose tolerance by increasing plasma
insulin clearance and depressing insulin secretion, namely first-phase and beta
cell glucose sensitivity.

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