The metabolism of lipids in mouse pancreatic islets. The oxidation of fatty acids and ketone bodies

Berne, Christian

doi:10.1042/bj1520661

Cited by 77 publications

(46 citation statements)

References 44 publications

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“…Islets express low-density lipoprotein receptors (Grupping et al 1997) and lipoprotein lipase (Cruz et al 2001) and may therefore obtain fatty acids from lipoprotein particles. However, free fatty acids are also taken up and stored or oxidised by islets (Berne 1975b). Exposure of islets to fatty acids has marked effects on secretory function.…”

Section: Discussionmentioning

confidence: 99%

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

Gravena

Mathias²,

Ashcroft

2002

Journal of Endocrinology

139

107

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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.

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Section: Discussionmentioning

confidence: 99%

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

Gravena

Mathias²,

Ashcroft

2002

Journal of Endocrinology

139

107

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“…Glucose-induced insulin secretion is associated not only with inhibition of FFA oxidation, but also increased FFA esterification, and complex lipid synthesis by pancreatic b-cells (Prentki and Corkey, 1996). Significant increases occur in the total mass of diacylglycerol (DAG) (PeterRiesch et al, 1988), triacylglycerol (Berne, 1975), and phosphatidic acid (PA) (Farese et al, 1986). Recently, we have shown that pancreatic islets are able to convert glucose into fatty acids (FA) by de novo synthesis (unpublished data).…”

Section: Glucose As Lipid Precursors In B-cellmentioning

confidence: 99%

Pleiotropic effects of fatty acids on pancreatic β‐cells

Haber

Ximenes

Procópio

et al. 2002

Journal Cellular Physiology

148

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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.

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“…Les acides gras sont des substrats énergétiques majeurs de la cellule β des îlots de Langerhans [17,18]; ils stimulent l'insulinosécrétion en présence de concentrations normales ou élevées de glucose sanguin. Les effets insulinosécréteurs des acides gras sont néanmoins faibles par rapport à leur contribution au métabolisme oxydatif des cellules β. Les acides gras utilisés par les cellules β ont plusieurs origines: les acides gras libres circulants, les acides gras contenus dans les lipoprotéines circulantes (les cellules β possèdent des récepteurs des LDL qui leur permettent de capter les lipoprotéines circulantes [19]) et les acides gras contenus dans les triglycérides stockés dans la cellule β.…”

Section: Les Acides Gras Libres Sont Des Substrats Normaux Des Cellulunclassified

Rôle des acides gras libres dans la sécrétion et l’action de l’insuline : mécanismes de la lipotoxicité

Girard¹

2003

Med Sci (Paris)

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The metabolism of lipids in mouse pancreatic islets. The oxidation of fatty acids and ketone bodies

Cited by 77 publications

References 44 publications

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

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

Pleiotropic effects of fatty acids on pancreatic β‐cells

Rôle des acides gras libres dans la sécrétion et l’action de l’insuline : mécanismes de la lipotoxicité

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