Acute effects of fatty acids on insulin secretion from rat and human islets of Langerhans

Abstract

Fatty acids have both stimulatory and inhibitory effects on insulin secretion. Long-term exposure to fatty acids results in impaired insulin secretion whilst acute exposure has generally been found to enhance insulin release. However, there are conflicting data in the literature as to the relative efficacy of various fatty acids and on the glucose dependency of the stimulatory effect. Moreover, there is little information on the responses of human islets in vitro to fatty acids. We have therefore studied the acute effects of a range of fatty acids on insulin secretion from rat and human islets of Langerhans at different glucose concentrations.Fatty acids (0·5 mM) acutely stimulated insulin release from rat islets of Langerhans in static incubations in a glucose-dependent manner. The greatest effect was seen at high glucose concentration (16·7 mM) and little or no response was elicited at 3·3 or 8·7 mM glucose. Longchain fatty acids (palmitate and stearate) were more effective than medium-chain (octanoate). Saturated fatty acids (palmitate, stearate) were more effective than unsaturated (palmitoleate, linoleate, elaidate). Stimulation of insulin secretion by fatty acids was also studied in perifused rat islets. No effects were observed at 3·3 mM glucose but fatty acids markedly potentiated the effect of 16·7 mM glucose. The combination of fatty acid plus glucose was less effective when islets had been first challenged with glucose alone. The insulin secretory responses to fatty acids of human islets in static incubations were similar to those of rat islets. In order to examine whether the responses to glucose and to fatty acids could be varied independently we used an animal model in which lactating rats are fed a low-protein diet during early lactation. Islets from rats whose mothers had been malnourished during lactation were still able to respond effectively to fatty acids despite a lowered secretory response to glucose.These data emphasise the complex interrelationships between nutrients in the control of insulin release and support the view that fatty acids play an important role in glucose homeostasis during undernutrition.

HPA axis and vagus nervous function are involved in impaired insulin secretion of MSG-obese rats

“…Pancreatic islets were isolated from operated or shamoperated rats using a collagenase enzyme technique as previously described, with some adaptation (Gravena et al 2002). At 100 days of age, after being anesthetized with 45 mg/kg BW thiopental, the rats were decapitated and the abdominal wall was cut open.…”

Poor pubertal protein nutrition disturbs glucose-induced insulin secretion process in pancreatic islets and programs rats in adulthood to increase fat accumulation

“…Pancreatic islets were isolated by a collagenase technique as previously described (Gravena et al 2002) …”

Fatty acid metabolism and insulin secretion in pancreatic beta cells

“…The rapid effect of NEFA to potentiate GSIS in vitro, while having little effect on secretion at non-stimulatory glucose concentrations, would suggest that they act as incretins [25,31,78,79,80]. This effect has also been documented in vivo, where NEFA increase serum insulin concentrations in animals [81] and humans [82].…”

“…Another possibility is that the LC-CoA derivative of the fatty acid directly modulates multiple effector systems in stimulating secretion [31,63,69,77,85] or that its esterification into complex lipids provides the necessary signalling factors in potentiating secretion [29,78,83,86,87,88]. Several descriptive studies dealing with extracellular NEFA have shown that an increase in chain length, peaking around C16, and increasing saturation correlates with an increase in insulinotropic action of NEFA [80,89,90].…”