Effects of fatty acids on insulin secretion

As well as evidence for FFA modulation of energy metabolism and insulin action at cellular level, there is also increasing evidence to support the view that the amount and type of fatty acids influence the secretion of insulin, and in particular, modulate glucose-stimulated insulin secretion (GSIS). This appears to be an important physiological response which ensures insulin secretion is enhanced in situations where glucose uptake and oxidation could otherwise be compromised owing to inhibitory effects of high circulating FFA levels (via the glucose fatty acid cycle). There may also be fatty acid specific effects since in both human and rat islets, saturated fats (SFA) cause greater potentiation of GSIS compared with unsaturated fatty acids, as do long chain fatty acids compared with medium chain fatty acids (Gravena et al., 2002). However, this specificity is not confirmed as relevant human studies that could demonstrate this in vivo have not been carried out. It is important to note that this ability of fatty acids to stimulate insulin secretion, and thereby control blood glucose levels when fatty acid and glucose levels are simultaneously raised is limited. Indeed as described later, there is evidence that following chronic exposure fatty acids may also reduce insulin secretion.

The mechanism by which fatty acids cause stimulation of insulin secretion appears to be via increased intracellular LC acyl CoA (Yaney & Corkey, 2003; Roduit et al., 2004). LC acyl CoA are thought to act as lipid signalling factors for cellular processes such as exocytosis in the beta-cell and manipulation of beta-cell LC acyl CoA or malonyl CoA levels has been shown to promote insulin secretion (Chen et al., 1994; Zhang & Kim, 1998). Some fatty acids may also alter insulin secretion via direct modulation of ion channel activity, with myristic acid shown to increase both K+ and Ca2+ channel activity, while arachidonic acid may increase Ca2+ entry through indirect effects, following conversion to prostaglandins PGI2 or PGE2 (Haber et al., 2002). Palmitate also appears to enhance insulin secretion via acylation of membrane proteins which promote Ca2+ dependent insulin secretion (Yajima et al., 2000; Haber et al., 2002).

Supplements For Diabetics

Supplements For Diabetics

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