Haber E P, Ximenes H M A, Procópio J, Carvalho C R O, Curi R, Carpinelli A R
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Brazil.
J Cell Physiol. 2003 Jan;194(1):1-12. doi: 10.1002/jcp.10187.
Hyperlipidemia is frequently associated with insulin resistance states as found in type 2 diabetes and obesity. Effects of free fatty acids (FFA) on pancreatic beta-cells have long been recognized. Acute exposure of the pancreatic beta-cell to FFA results in an increase of insulin release, whereas a chronic exposure results in desensitization and suppression of secretion. We recently showed that palmitate augments insulin release in the presence of non-stimulatory concentrations of glucose. Reduction of plasma FFA levels in fasted rats or humans severely impairs glucose-induced insulin release. These results imply that physiological plasma levels of FFA are important for beta-cell function. Although, it has been accepted that fatty acid oxidation is necessary for its stimulation of insulin secretion, the possible mechanisms by which fatty acids (FA) affect insulin secretion are discussed in this review. Long-chain acyl-CoA (LC-CoA) controls several aspects of the beta-cell function including activation of certain types of protein kinase C (PKC), modulation of ion channels, protein acylation, ceramide- and/or nitric oxide (NO)-mediated apoptosis, and binding to nuclear transcriptional factors. The present review also describes the possible effects of FA on insulin signaling. We showed for the first time that acute exposure of islets to palmitate upregulates the intracellular insulin-signaling pathway in pancreatic islets. Another aspect considered in this review is the source of FA for pancreatic islets. In addition to be exported to the medium, lipids can be transferred from leukocytes (macrophages) to pancreatic islets in co-culture. This process consists an additional source of FA that may plays a significant role to regulate insulin secretion.
高脂血症常与2型糖尿病和肥胖症等胰岛素抵抗状态相关。游离脂肪酸（FFA）对胰腺β细胞的影响早已为人所知。胰腺β细胞急性暴露于FFA会导致胰岛素释放增加，而慢性暴露则会导致脱敏和分泌抑制。我们最近发现，在非刺激浓度的葡萄糖存在下，棕榈酸酯会增强胰岛素释放。禁食大鼠或人类血浆FFA水平的降低会严重损害葡萄糖诱导的胰岛素释放。这些结果表明，生理水平的血浆FFA对β细胞功能很重要。尽管人们已经认识到脂肪酸氧化对于刺激胰岛素分泌是必要的，但本综述讨论了脂肪酸（FA）影响胰岛素分泌的可能机制。长链酰基辅酶A（LC-CoA）控制β细胞功能的多个方面，包括某些类型的蛋白激酶C（PKC）的激活、离子通道的调节、蛋白质酰化、神经酰胺和/或一氧化氮（NO）介导的细胞凋亡以及与核转录因子的结合。本综述还描述了FA对胰岛素信号传导的可能影响。我们首次表明，胰岛急性暴露于棕榈酸酯会上调胰腺胰岛细胞内的胰岛素信号通路。本综述考虑的另一个方面是胰腺胰岛的FA来源。除了分泌到培养基中，脂质还可以在共培养中从白细胞（巨噬细胞）转移到胰腺胰岛。这个过程构成了FA的另一个来源，可能在调节胰岛素分泌中发挥重要作用。
