LIPID-DIABET

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 该方案研究了在高血糖钳夹期间通过脂内/肝素共同输注来调节脂肪酸水平时，增加的游离脂肪酸对正常受试者内源性胰岛素分泌以及胰岛素和C肽清除的影响。我们证实，在这些正常志愿者中，游离脂肪酸的增加会导致高胰岛素血症。与既定的教条相反，我们发现高胰岛素血症完全是由于胰岛素总清除率的下降；胰岛素分泌率没有变化。这一结果可能也可能不限于高度不饱和脂肪，因为脂肪内脂是高度不饱和脂肪的来源。 有些令人惊讶的是，与上面提到的放射免疫分析结果相反，在接受脂肪/肝素注射以提高血浆FFA的受试者中，表明事实上C肽清除量增加了约20%(107.6±4.7vs87.8ml/m2/m2/min；IDAvs放射免疫分析方法，p&lt；0.05)我们认为这种差异可能是由于高脂血症对放射免疫分析中抗原/抗体结合的基质影响。由于RIA方法的对数性质，由于脂肪酸/脂肪洗涤剂的作用，抗体/抗原结合亲和力的微小下降很容易导致C-肽浓度增加20%-30%。这强调了同位素稀释分析的有用性，以避免免疫分析方法的分析物测量中的人为变化。最终的结果是，同位素稀释法似乎本质上不太容易出现测量伪影。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This protocol investigates the role of increased free fatty acids on endogenous insulin secretion and insulin and C-peptide clearance in normal subjects when fatty acid levels are manipulated by co-infusion of intralipid/heparin during hyperglycemic clamp. We confirm that increases in free fatty acids results in hyperinsulinemia in these normal volunteers. Contrary to established dogma, we have found that the hyperinsulinemia is entirely due to decreases in total clearance rate of insulin; there is no change in insulin secretory rates. This result may or may not be restricted to highly unsaturated fats since intralipid is a highly unsaturated source of fat. Somewhat surprisingly, and in contrast to the RIA results noted above, in subjects undergoing intralipid/heparin infusion to raise plasma FFA, suggests that in fact C-peptide clearance is increasing by ~20% (107.6 ¿ 4.7 vs 87.3 ¿ 7.8 ml/m2/m2/min; IDA vs RIA methods, p<.05) We believe this disparity is likely due to matrix affects of hyperlipidemia on antigen/antibody binding in the RIA. Small decreases in antibody/antigen binding affinity due to fatty acid/lipid detergent effects could easily result in 20-30% higher C-peptide concentrations due to the logarithmic nature of RIA methods. This emphasizes the usefulness of isotope dilution assays to avoid artifactual changes in analyte measurements by immunoassay methods. The net result is that the isotope dilution assay appears to be intrinsically less prone to artifacts of measurement.