Pleiotropic effects of fatty acids on pancreatic β‐cells

Abstract

Hyperlipidemia is frequently associated with insulin resistance states as found in type 2 diabetes and obesity. Effects of free fatty acids (FFA) on pancreatic b-cells have long been recognized. Acute exposure of the pancreatic b-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 b-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 acylCoA (LC-CoA) controls several aspects of the b-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.

Adiponectin counteracts cytokine- and fatty acid-induced apoptosis in the pancreatic beta-cell line INS-1

“…Cytokines and palmitic acid induced a marked (two-three fold) decrease of glucose/forskolin-stimulated insulin release ( Fig. 5), in complete agreement with recently published data [23,26,27,29,32]. Neither IL-1β/IFN-γ nor palmitic acid affected basal insulin secretion under our experimental conditions (Fig.…”

“…There is increasing evidence that acute exposure of pancreatic beta cells to high concentrations of fatty acids results in an increase of insulin release, whereas chronic exposure induces desensitization and suppression of secretion [28,29], possibly contributing to the progressive beta-cell dysfunction in Type 2 diabetes.…”

Free fatty acid receptor 1 (FFA1R/GPR40) and its involvement in fatty-acid-stimulated insulin secretion

“…Medium-chain to long-chain fatty acids (FAs) are known to have pleiotropic effects on the pancreatic β-cell; while acute administration of FFAs stimulates insulin release (Haber et al 2003), long-term exposure to high levels of FFAs results in impairment of the β-cell secretory capacity (Salehi et al 2003, Salehi et al 2001, Bollheimer et al 1998), often associated with type 2 diabetes. The secretory response is strongly dependent on the metabolic status of the β-cell.…”

Insulin-stimulating diets during the weaning-to-estrus interval do not improve fetal and placental development and uniformity in high-prolific multiparous sows

“…probably resulted in short-term increases in plasma free fatty acid levels before morning feeding (Barb et al, 1997;Inoue et al, 2005), which in turn can stimulate glucose-stimulated insulin secretion (Haber et al, 2003;Itoh et al, 2003). As insulin responses differ between morning and afternoon feedings, studies investigating effects of insulin on, for example, follicle development should consider both insulin responses.…”