Beysen C, Karpe F, Fielding B A, Clark A, Levy J C, Frayn K N
Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Infirmary, Oxford, UK.
Diabetologia. 2002 Nov;45(11):1533-41. doi: 10.1007/s00125-002-0964-9. Epub 2002 Oct 2.
AIMS/HYPOTHESIS: Fatty acids affect insulin secretion in vivo, but little is known about the effects of specific fatty acids. Our aim was to investigate differential effects of acutely increased plasma monounsaturated, polyunsaturated and saturated fatty acids on glucose-stimulated insulin secretion in healthy humans.
A new experimental protocol was used to increase plasma monounsaturated (MUFA test), polyunsaturated (PUFA test) or saturated (SFA test) non-esterified fatty acids for 2 h by repeated oral fat feeding and continuous intravenous heparin infusion. This was followed by a hyperglycaemic clamp (10 mmol/l) to test insulin secretion in response to a prior plasma NEFA increase.
Total plasma NEFA concentrations were increased during the fat tests compared to the control visit (1.7-fold increase for MUFA and SFA tests and 1.4-fold increase for PUFA test; p<0.001). Exaggerated responses in plasma insulin, C-peptide and proinsulin concentrations were seen during the hyperglycaemic clamp after increasing plasma NEFA concentrations compared with the control (p<0.01). The effects were greatest for the MUFA test followed by the PUFA test and SFA test (p<0.01). Plasma GLP-1 concentrations increased during fat feeding, with a higher response during the MUFA test compared to PUFA and SFA tests (p<0.01).
CONCLUSION/INTERPRETATION: Increasing plasma NEFA concentrations by oral fat feeding with heparin infusion augments glucose-stimulated insulin secretion with the greatest effect for monounsaturated fatty acids and the lowest effect for saturated fatty acids. Monounsaturated fatty acids also increase GLP-1 more than saturated fatty acids. Therefore, the exaggerated insulin concentrations could be due to both NEFA and GLP-1.
目的/假设：脂肪酸在体内会影响胰岛素分泌，但对于特定脂肪酸的影响却知之甚少。我们的目的是研究急性升高的血浆单不饱和脂肪酸、多不饱和脂肪酸和饱和脂肪酸对健康人体葡萄糖刺激的胰岛素分泌的不同影响。
采用一种新的实验方案，通过重复口服脂肪喂养和持续静脉输注肝素，使血浆单不饱和脂肪酸（MUFA试验）、多不饱和脂肪酸（PUFA试验）或饱和脂肪酸（SFA试验）非酯化脂肪酸升高2小时。随后进行高血糖钳夹（10 mmol/L），以测试在先前血浆非酯化脂肪酸升高后胰岛素的分泌情况。
与对照访视相比，在脂肪试验期间总血浆非酯化脂肪酸浓度升高（MUFA试验和SFA试验升高1.7倍，PUFA试验升高1.4倍；p<0.001）。与对照相比，在血浆非酯化脂肪酸浓度升高后的高血糖钳夹期间，血浆胰岛素、C肽和胰岛素原浓度出现过度反应（p<0.01）。MUFA试验的影响最大，其次是PUFA试验和SFA试验（p<0.01）。在脂肪喂养期间血浆胰高血糖素样肽-1（GLP-1）浓度升高，与PUFA试验和SFA试验相比，MUFA试验期间的反应更高（p<0.01）。
结论/解读：通过口服脂肪喂养并输注肝素提高血浆非酯化脂肪酸浓度，可增强葡萄糖刺激的胰岛素分泌，对单不饱和脂肪酸的影响最大，对饱和脂肪酸的影响最小。单不饱和脂肪酸比饱和脂肪酸也能更多地增加GLP-1。因此，胰岛素浓度的过度升高可能是由于非酯化脂肪酸和GLP-1共同作用的结果。
