The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation.

Stein, Daniel T.; Stevenson, B E; Chester, Michael R.; Basit, Mujeeb; Daniels, M B; Turley, Stephen D.; McGarry, Julie

doi:10.1172/jci119546

Cited by 305 publications

(274 citation statements)

References 30 publications

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“…In these studies, GLP-1 concentrations are probably not increased (although not usually measured) and therefore favour a direct role for NEFA in the regulation of insulin secretion. Also, the marked stimulatory effect on insulin secretion of saturated fatty acids compared to other fatty acids seen in vitro [19] was completely absent in vivo, again showing the complexity of the in vivo situation.…”

Section: Discussionmentioning

confidence: 95%

“…From numerous isolated islet studies it has become clear that fatty acids have a direct effect on the beta cell and that short-term incubation of fatty acids gives rise to an amplified insulin response, increasing with chain length and degree of saturation [10,19]. A direct stimulatory effect of fatty acids upon islets provides a plausible explanation for the greater insulinotropic effect with increased NEFA concentrations, as seen in this study, although in vivo, other factors, such as insulin sensitivity, hepatic insulin clearance and other stimulants have to be considered.…”

Section: Discussionmentioning

confidence: 99%

“…At the cellular level, glucose-stimulated insulin release has been shown to be more pronounced with increasing chain length and the degree of saturation of the fatty acids in acute incubations in vitro [17,18]. In particular, stearic and palmitic acid have marked stimulatory effects on glucose-stimulated insulin secretion from perfused rat pancreas [19]. Results from these in vitro studies cannot necessarily be extrapolated to the situation in vivo.…”

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Interaction between specific fatty acids, GLP-1 and insulin secretion in humans

et al. 2002

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Aims/hypothesis. Fatty acids affect insulin secretion in vivo, but little is known about the effects of specific fatty acids. Our aim was to investigate differential effects of acutely increased plasma monounsaturated, polyunsaturated and saturated fatty acids on glucosestimulated insulin secretion in healthy humans. Methods. A new experimental protocol was used to increase plasma monounsaturated (MUFA test), polyunsaturated (PUFA test) or saturated (SFA test) nonesterified fatty acids for 2 h by repeated oral fat feeding and continuous intravenous heparin infusion. This was followed by a hyperglycaemic clamp (10 mmol/l) to test insulin secretion in response to a prior plasma NEFA increase. Results. Total plasma NEFA concentrations were increased during the fat tests compared to the control visit (1.7-fold increase for MUFA and SFA tests and 1.4-fold increase for PUFA test; p<0.001). Exaggerated responses in plasma insulin, C-peptide and proinsulin concentrations were seen during the hyperglycaemic clamp after increasing plasma NEFA concentrations compared with the control (p<0.01). The effects were greatest for the MUFA test followed by the PUFA test and SFA test (p<0.01). Plasma GLP-1 concentrations increased during fat feeding, with a higher response during the MUFA test compared to PUFA and SFA tests (p<0.01). Conclusion/interpretation. Increasing plasma NEFA concentrations by oral fat feeding with heparin infusion augments glucose-stimulated insulin secretion with the greatest effect for monounsaturated fatty acids and the lowest effect for saturated fatty acids. Monounsaturated fatty acids also increase GLP-1 more than saturated fatty acids. Therefore, the exaggerated insulin concentrations could be due to both NEFA and GLP-1. [Diabetologia (2002[Diabetologia ( ) 45:1533[Diabetologia ( -1541 Keywords Monounsaturated fatty acids, polyunsaturated fatty acids, saturated fatty acids, insulin secretion, GLP-1. High fat diets lead to obesity, which in turn is one of the main causes of the development of Type II (noninsulin-dependent) diabetes mellitus. Both obesity and Type II diabetes are characterized by increased plasma non-esterified fatty acid concentrations [1] and raised fasting plasma NEFA concentrations are a risk marker for the development of Type II diabetes in Caucasian subjects [2] and in Pima Indians [3]. Increased plasma NEFA concentrations can have adverse effects on various tissues. Excess plasma NEFA concentrations can lead to a reduced skeletal muscle glucose uptake and oxidation [4,5,6], increased hepatic glucose output [7] and a decrease in hepatic insulin clearance [8,9]. These mechanisms could lead to glucose intolerance and insulin resistance leading to Type II diabetes.Inappropriately high concentrations of plasma NEFA have also been shown to alter glucose-stimulat-

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Interaction between specific fatty acids, GLP-1 and insulin secretion in humans

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“…Also, circulating fatty acids, both observationally and experimentally, seem closely involved in the pathogenesis of type 2 diabetes [31,33]. Depending on chain length, fatty acids also stimulate insulin secretion [34,35], which may further aggravate hepatic insulin resistance [36]. The fall in NEFA after glucose challenge between the sites (Fig.…”

Section: Discussionmentioning

confidence: 99%

Marked differences in the IGF system that are associated with migration in comparable populations of Gujaratis living in Sandwell, UK, and Gujarat, India

et al. 2005

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Aims/hypotheses: We previously reported independent links between the IGF system and the development of impaired glucose tolerance and cardiovascular risk. This study tests the hypothesis that the lifestyle change which accompanies population migration, with attendant increases in cardiovascular risk, is reflected by changes in the IGF system. Materials and methods: We compared a specific Gujarati community in Sandwell, UK (n=205), with people still resident in the same villages of origin near Navsari, India (n=246). We performed anthropometry and measured fasting plasma insulin, IGF-I, insulin-like growth factor binding protein (IGFBP)-1 and IGFBP-3. Results: Daily calorie intake, BMI and WHR were significantly higher in UK Gujaratis than in Indian Gujaratis. IGFBP-1 was significantly lower in UK migrants (mean 29.5 [95% CI 25.9-33.0] vs 56.5 [50.6-62.5]μg/l; F=48.4, p<0.001). Conversely, fasting insulin, IGFBP-3 and IGF-I were all higher in UK Gujaratis (mean IGF-I 145.9 [138.1-153.6]ng/ml in UK Gujaratis and 100.9 [94.6-107.3] ng/ml in Navsari Gujaratis; F=76.6, p<0.001). These differences were still apparent when adjustment was made for BMI by location for IGF-I (F=57.4, p<0.001) and IGFBP-3 (F=5.7, p=0.02), but were no longer apparent for IGFBP-1 and insulin. At the population level, the decrease in IGFBP-1 for a given increase in insulin was significantly smaller in UK Gujaratis, suggesting greater hepatic insulin resistance in this group. Conclusions/interpretation: Environmental factors have profound effects on circulating IGF system components and on the relationship between IGFBP-1, IGF-I and related metabolic variables. This may have long-term implications for the development of worsening glucose tolerance and cardiovascular disease.

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“…The role of FA in the process of glucoseinduced insulin secretion has been investigated by several groups (Opara et al, 1992(Opara et al, , 1994Stein et al, 1996Stein et al, , 1997Boden et al, 1998). The potency of FA to promove glucose-induced insulin release increases with the chain length and decreases with the degree of unsaturation (Opara et al, 1994;Dobbins et al, 1997).…”

Section: Plasma Fa and Insulin Secretionmentioning

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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The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation.

Cited by 305 publications

References 30 publications

Interaction between specific fatty acids, GLP-1 and insulin secretion in humans

Interaction between specific fatty acids, GLP-1 and insulin secretion in humans

Marked differences in the IGF system that are associated with migration in comparable populations of Gujaratis living in Sandwell, UK, and Gujarat, India

Pleiotropic effects of fatty acids on pancreatic β‐cells

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