Stereospecific effects of fatty acids on proglucagon-derived peptide secretion in fetal rat intestinal cultures.

Rocca, Antonio S.; Brubaker, Patricia L.

doi:10.1210/endo.136.12.7588313

Cited by 94 publications

(53 citation statements)

References 36 publications

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“…Similar studies have demonstrated synergistic effects of the monounsaturated fatty acid oleic acid and the enteroendocrine hormone glucose-dependent insulinotropic peptide in the regulation of GLP-1 secretion by GLUTag cells (48,54). In the in vivo setting, GLP-1 is rapidly secreted by L cells upon ingestion of a meal, and by fat and glucose in particular (3)(4)(5), as was also shown in the present study.…”

Section: Discussionsupporting

confidence: 90%

“…Previous studies have demonstrated that alterations in the fat composition of rodent chow, while maintaining fat content at 5%, do not alter GLP-1 concentrations in the ileum of rats (57), although dietary fat does stimulate GLP-1 release from the intestinal L cell (3,37,40,54). The mechanism(s) by which fat enhances the synthesis and secretion of GLP-1 remains to be determined.…”

Section: Discussionmentioning

confidence: 98%

“…In the in vivo setting, GLP-1 is rapidly secreted by L cells upon ingestion of a meal, and by fat and glucose in particular (3)(4)(5), as was also shown in the present study. Both direct effects of nutrients on the L cell and indirect effects involving endocrine and neuronal mediators, including GRP (3,40,48,54), have been shown to be involved in this secretion. As a consequence, GLP-1 release is biphasic, with the indirect effects occurring rapidly (15-30 min) and the direct effects taking place much later (60 -120 min) after a meal (4,5).…”

Section: Discussionmentioning

confidence: 99%

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Role of Leptin in the Regulation of Glucagon-Like Peptide-1 Secretion

2003

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T he hormone glucagon-like peptide-1 (GLP-1) is secreted from enteroendocrine L cells, which are localized in the distal ileum and colon (1), after nutrient ingestion (2-5). GLP-1 acts through a specific G-protein-coupled receptor to potently stimulate glucose-dependent insulin secretion (6 -8). GLP-1 further reduces glycemia through inhibition of both glucagon secretion (9) and gastric emptying (10) and by stimulation of pancreatic ␤-cell proliferation and neogenesis (11,12). The GLP-1 receptor is also expressed in hypothalamic nuclei that are responsible for modulating feeding behavior (13,14), and central GLP-1 administration reduces food intake in rodents, whereas peripheral administration of GLP-1 promotes satiety and decreases body weight in humans (13,15). These pleiotropic actions of GLP-1 therefore offer great potential for the treatment of hyperglycemia in patients with type 2 diabetes (1,15).It has recently been shown that plasma GLP-1 levels are reduced in obesity (16 -19), a condition that is highly correlated to type 2 diabetes (20). The mechanisms leading to decreased GLP-1 secretion in obesity have not been elucidated. However, because plasma leptin levels are proportional to fat mass, we postulated the existence of an adipo-enteroendocrine interaction between leptin and GLP-1. Leptin, a product of the ob gene in white adipose tissue, activates hypothalamic circuits, leading to the inhibition of food intake (21,22). The leptin receptor gene encodes five alternatively spliced forms of mRNA (23,24). However, only the long form of the leptin receptor (ObRb) contains an intracellular JAK-STAT signaling motif, and Ob-Rb appears to be responsible for the physiological actions of leptin (25-27). Although Ob-Rb is predominantly distributed in the ventral medial hypothalamic region known to be important in determining feeding behavior (21,28), it is now recognized that Ob-Rb is also expressed in several peripheral tissues, including the gut and the pancreas (29 -31).It has been shown that ob/ob mice, which are homozygous for a mutation of the ob gene, and db/db mice, which have a mutation in the leptin receptor, both exhibit hyperphagia and morbid obesity, leading to hyperinsulinemia and hyperglycemia (22,23). Although ob/ob and db/db mice serve as models of type 2 diabetes, human ob or db gene mutations are extremely rare, and no linkages with diabetes have been found (32,33). Nonetheless, most obese humans exhibit hyperleptinemia, and increased adiposity is believed to occur in association with the development of leptin resistance (21,32,33). One model of leptin resistance is the C57BL/6 mouse submitted to a high-fat diet (34). In contrast to the ob/ob and db/db mice, these mice develop impaired glucose tolerance but seldom progress to frank diabetes. We now demonstrate that leptin stimulates GLP-1 secretion from enteroendocrine L cells in vitro and in vivo and, furthermore, that leptin resistance in obese C57BL/6 mice is associated with impaired secretion of GLP-1. RESEARCH DESIGN AND METHODSCell cultu...

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Role of Leptin in the Regulation of Glucagon-Like Peptide-1 Secretion

2003

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“…After a mixed meal, the plasma GLP-1 increase has also been shown to be more pronounced with the presence of olive oil than palm oil or butter in healthy humans [39]. Also, in vitro, oleic acid is a stronger stimulator of GLP-1 secretion than saturated fatty acids [52]. The marked increase in GLP-1 at basal glucose concentrations coincided with only a very small increase in plasma insulin concentrations for the three fat tests compared to the control visit.…”

Section: Discussionmentioning

confidence: 99%

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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“…A study in diabetic mice showed that a high-MUFA diet with a controlled caloric intake could ameliorate impaired glucose tolerance [14]. The mechanism of glucose-lowering action by MUFAs is proposed to be through the reversal of decreased activity of glucokinase, a key enzyme in the catabolism of glucose [15], and through the activation of glucagon-like peptide-1 secretion [16,17], which stimulates glucose-dependent insulin secretion and inhibits food intake.…”

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confidence: 99%

A high-MUFA diet alone does not affect ketone body metabolism, but reduces glycated hemoglobin when combined with exercise training in diabetic rats

et al. 2015

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Background: Monounsaturated fat (MUFA) also has glucose-lowering action, but its effect on ketone bodies is unknown. Objectives: To examine the effects of high-MUFA diet alone or in combination with exercise training, which can improve glucose and ketone body metabolism, in a rat model of diabetes. Methods: Wistar rats were administered streptozotocin to induce diabetes and then randomly divided into five groups: sedentary rats fed a regular diet (1), a high-saturated-fat diet (2), a high-MUFA diet (3); and exercisetrained rats fed a regular diet (4), and a high-MUFA diet (5). Training was by a treadmill twice daily, 5 days/week. At 12 weeks, glucose, glycated hemoglobin (HbA 1c ), insulin, nonesterified fatty acids (NEFA), and β-hydroxybutyrate levels were measured in cardiac blood. Activity of the overall ketone synthesis pathway was determined in liver and 3-ketoacyl-CoA transferase activity determined in gastrocnemius muscle. Results: A high-MUFA diet tended to lower plasma glucose without affecting other biochemical variables. Training did not change glucose metabolism, but significantly reduced serum NEFA. Only the high-MUFA diet plus training significantly decreased HbA 1c levels. Hepatic ketone synthesis was decreased and 3-ketoacyl-CoA transferase activity was increased by training alone or in combination with a high-MUFA diet. Changes in NEFA, β-hydroxybutyrate, and the enzymatic activities in response to training plus a high-MUFA diet were comparable to those caused by training alone. Conclusion: A high-MUFA diet alone does not alter ketone body metabolism. Combination of a MUFA-rich diet and exercise training is more effective than either MUFA or exercise alone for lowering HbA 1c .

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Stereospecific effects of fatty acids on proglucagon-derived peptide secretion in fetal rat intestinal cultures.

Cited by 94 publications

References 36 publications

Role of Leptin in the Regulation of Glucagon-Like Peptide-1 Secretion

Role of Leptin in the Regulation of Glucagon-Like Peptide-1 Secretion

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

A high-MUFA diet alone does not affect ketone body metabolism, but reduces glycated hemoglobin when combined with exercise training in diabetic rats

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