Article

Palmitate potentiation of glucose-induced insulin release: a study using 2-bromopalmitate.

Pacific Nortwest Research Institute, Seattle, WA 98122, USA.
Metabolism (Impact Factor: 3.61). 10/2003; 52(10):1367-71. DOI: 10.1016/S0026-0495(03)00279-8
Source: PubMed

ABSTRACT The mechanisms whereby fatty acids (FA) potentiate glucose-induced insulin secretion from the pancreatic beta cell are incompletely understood. In this study, the effects of palmitate on insulin secretion were investigated in isolated rat islets. Palmitate did not initiate insulin secretion at nonstimulatory glucose concentrations, but markedly stimulated insulin release at concentrations of glucose > or = 5.6 mmol/L. At concentrations of palmitate > or =0.5 mmol/L, the important determinant of the potency of the FA was its unbound concentration. At total concentrations < or = 0.5 mmol/L, both the total and unbound concentrations appeared important. Surprisingly, 2-bromopalmitate did not affect palmitate oxidation, but significantly diminished palmitate esterification into cellular lipids. Neither methyl palmitate, which is not activated into a long-chain acyl-CoA ester, nor 2-bromopalmitate affected glucose-stimulated insulin release. Further, 2-bromopalmitate partly inhibited the potentiating effect of palmitate. These results support the concept that FA potentiation of insulin release is mediated by FA-derived signals generated in the esterification pathway.

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    • "The agonist properties of partial agonists, such as 2BrP, will appear more pronounced in a recombinant system with higher receptor density (Kenakin 1997). We were also able to confirm earlier reports (Parker et al. 2003; Warnotte et al. 1994) showing that while 2BrP inhibits LA-stimulated insulin release in mouse islets, the LC-CoA synthetase inhibitor triacsin C was without effect. The fact that 2BrP not only appears as an inhibitor of FA-mediated insulin release but has now also been identified as an antagonist/partial agonist of FFA 1 R/GPR40 provides a pharmacological support for our view that FFA 1 R/GPR40 is an essential link in the mechanism underlying the FA-mediated potentiation of insulin secretion. "
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    • "There is no evidence of a connection between palmitate and plasma glucose homeostasis . However, ourselves and others (Parker et al., 2003) have shown that that palmitate weakly stimulates insulin secretion, but this is only at concentrations as high as 1 mM (data not shown). An alternative possibility would be that the palmitate derivatised GLP-1 analogues have additional hyperglycaemic actions due to for example , stimulation of glucagon secretion. "
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