Inhibition of carbohydrate-mediated glucagon-like peptide-1 (7‒36)amide secretion by circulating non-esterified fatty acids

1999 ◽  
Vol 96 (4) ◽  
pp. 335 ◽  
Author(s):  
L. RANGANATH ◽  
F. NORRIS ◽  
L. MORGAN ◽  
J. WRIGHT ◽  
V. MARKS
Keyword(s):  
Fatty Acids ◽  
Esterified Fatty Acids ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Inhibition of carbohydrate-mediated glucagon-like peptide-I (7–36)amide secretion by circulating non-esterified fatty acids

1999 ◽  
Vol 96 (4) ◽  
pp. 335-342
Author(s):  
L. RANGANATH ◽  
F. NORRIS ◽  
L. MORGAN ◽  
J. WRIGHT ◽  
V. MARKS
Keyword(s):  
Fatty Acids ◽  
Intrinsic Defect ◽  
Complete Suppression ◽  
Esterified Fatty Acids ◽  
Simple Obesity ◽  
Obese Subjects ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Pancreatic Hormone ◽  
Insulinotropic Effect

Two studies were performed to assess the entero-insular axis in simple obesity and the possible effect of variations in the level of circulating non-esterified fatty acids (NEFA) on one of the components of the entero-insular axis, glucagon-like peptide-1 [(7–36) amide]. In the first study, we compared the entero-pancreatic hormone response to oral carbohydrate in obese and lean women. Obese subjects demonstrated hyperinsulinaemia and impaired glucose tolerance but this was not associated with an increased secretion of either glucose-dependent insulinotropic polypeptide or glucagon-like peptide-1 (GLP-1). These findings therefore provide no support for the hypothesis that overactivity of the entero-insular axis contributes to the hyperinsulinaemia seen in obesity. Indeed, the plasma GLP-1 response to carbohydrate was markedly attenuated in obese subjects, confirming previous observations. In the second study, in which carbohydrate-stimulated GLP-1 responses were again evaluated in obese and lean women, circulating NEFA levels were modulated using either heparin (to increase serum NEFA) or acipimox (to reduce serum NEFA). Treatment with acipimox resulted in complete suppression of NEFA levels and in a markedly higher GLP-1 response than the response to carbohydrate alone or to carbohydrate plus heparin. We suggest that higher fasting and postprandial NEFA levels in obesity may tonically inhibit nutrient-mediated GLP-1 secretion, and that this results in attenuation of the GLP-1 response to carbohydrate. However, although serum NEFA levels post-acipimox were similarly suppressed in both lean and obese subjects, the GLP-1 response was again significantly lower in obese subjects, suggesting the possibility of an intrinsic defect of GLP-1 secretion in obesity. The reduction of GLP-1 levels in obesity may be important both in relation to its insulinotropic effect and to its postulated role as a satiety factor.

scholarly journals Glucagon-like peptide 1 abolishes the postprandial rise in triglyceride concentrations and lowers levels of non-esterified fatty acids in humans

Diabetologia ◽  
2006 ◽  
Vol 49 (3) ◽  
pp. 452-458 ◽  
Author(s):  
J. J. Meier ◽  
A. Gethmann ◽  
O. Götze ◽  
B. Gallwitz ◽  
J. J. Holst ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Esterified Fatty Acids ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Free fatty acids administered into the colon promote the secretion of glucagon-like peptide-1 and insulin

2006 ◽  
Vol 340 (1) ◽  
pp. 332-337 ◽  
Author(s):  
Tetsuya Adachi ◽  
Toshiki Tanaka ◽  
Kazuhisa Takemoto ◽  
Taka-aki Koshimizu ◽  
Akira Hirasawa ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

GLP-1 response to sequential mixed meals: influence of insulin resistance

2017 ◽  
Vol 131 (24) ◽  
pp. 2901-2910 ◽  
Author(s):  
Eleni Rebelos ◽  
Brenno Astiarraga ◽  
Roberto Bizzotto ◽  
Andrea Mari ◽  
Maria Laura Manca ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Release ◽  
Cell Function ◽  
Fasting Glucose ◽  
Insulin Resistant ◽  
Esterified Fatty Acids ◽  
Β Cell Function ◽  
Glucose Sensitivity ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Previous work has shown that potentiation of insulin release is impaired in non-diabetic insulin resistance; we tested the hypothesis that this defect may be related to altered glucagon-like peptide-1 (GLP-1) release. On consecutive days, 82 non-diabetic individuals, classified as insulin sensitive (IS, n=41) or insulin resistant (IR, n=41) by the euglycaemic clamp, were given two sequential mixed meals with standard (75 g, LCD) or double (150 g, HCD) carbohydrate content. Plasma glucose, insulin, C-peptide, non-esterified fatty acids (NEFA) and GLP-1 concentrations were measured; β-cell function (glucose sensitivity and potentiation) was resolved by mathematical modelling. Fasting GLP-1 levels were higher in IR than IS (by 15%, P=0.006), and reciprocally related to insulin sensitivity after adjustment for sex, age, fat mass, fasting glucose or insulin concentrations. Mean postprandial GLP-1 responses were tightly correlated with fasting GLP-1, were higher for the second than the first meal, and higher in IR than IS subjects but only with LCD. In contrast, incremental GLP-1 responses were higher during (i) the second than the first meal, (ii) on HCD than LCD, and (iii) significantly smaller in IR than IS independently of meal and load. Potentiation of insulin release was markedly reduced in IR vs IS across meal and carbohydrate loading. In the whole dataset, incremental GLP-1 was directly related to potentiation, and both were inversely related to mean NEFA concentrations. We conclude that (a) raised GLP-1 tone may be inherently linked with a reduced GLP-1 response and (b) defective post-meal GLP-1 response may be one mechanism for impaired potentiation of insulin release in insulin resistance.

scholarly journals Glucagon-Like Peptide 1: A Predictor of Type 2 Diabetes?

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Matthias Ploug Larsen ◽  
Signe Sørensen Torekov
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Fasting Glucose ◽  
Incretin Effect ◽  
Nonesterified Fatty Acids ◽  
Incretin Hormone ◽  
Pubmed Database ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Background. The incretin effect is impaired in patients with type 2 diabetes. Aim. To assess the relation between the incretin hormone GLP-1 and the prediabetic subtypes: impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and the combined IFG/IGT to investigate whether a low GLP-1 response may be a predictor of prediabetes in adults. Method. 298 articles were found using a broad search phrase on the PubMed database and after the assessment of titles and abstracts 19 articles were included. Results and Discussion. Studies assessing i-IFG/IFG and i-IGT/IGT found both increased, unaltered, and reduced GLP-1 levels. Studies assessing IFG/IGT found unaltered or reduced GLP-1 levels. When assessing the five studies with the largest sample size, it clearly suggests a decreased GLP-1 response in IFG/IGT subjects. Several other factors (BMI, glucagon, age, and nonesterified fatty acids (NEFA)), including medications (metformin), may also influence the secretion of GLP-1. Conclusion. This review suggests that the GLP-1 response is a variable in prediabetes possibly due to a varying GLP-1-secreting profile during the development and progression of type 2 diabetes or difference in the measurement technique. Longitudinal prospective studies are needed to assess whether a reduced GLP-1 response is a predictor of diabetes.

scholarly journals Short-Chain Fatty Acids Stimulate Glucagon-Like Peptide-1 Secretion via the G-Protein-Coupled Receptor FFAR2

Diabetes ◽  
2011 ◽  
Vol 61 (2) ◽  
pp. 364-371 ◽  
Author(s):  
G. Tolhurst ◽  
H. Heffron ◽  
Y. S. Lam ◽  
H. E. Parker ◽  
A. M. Habib ◽  
...  
Keyword(s):  
Fatty Acids ◽  
G Protein ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
G Protein Coupled Receptor ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
G Protein Coupled ◽  
Chain Fatty Acids

scholarly journals The impact of short-chain fatty acids on GLP-1 and PYY secretion from the isolated perfused rat colon

2018 ◽  
Vol 315 (1) ◽  
pp. G53-G65 ◽  
Author(s):  
Charlotte Bayer Christiansen ◽  
Maria Buur Nordskov Gabe ◽  
Berit Svendsen ◽  
Lars Ove Dragsted ◽  
Mette Marie Rosenkilde ◽  
...  
Keyword(s):  
Energy Source ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Rat Colon ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Free Fatty Acid Receptors ◽  
Chain Fatty Acids

The colonic epithelium harbors a large number of endocrine cells, but little is known about the endocrine functions of the colon. However, the high density of glucagon like peptide-1 (GLP-1)- and peptide-YY (PYY)-secreting L cells is of great interest because of the potential antidiabetic and antiobesity effects of GLP-1 and PYY. Short-chain fatty acids (SCFAs) produced by local bacterial fermentation are suggested to activate the colonic free fatty acid receptors FFAR2 (GPR43) and FFAR3 (GPR41), stimulating the colonic L cells. We used the isolated perfused rat colon as a model of colonic endocrine secretion and studied the effects of the predominant SCFAs formed: acetate, propionate, and butyrate. We show that luminal and especially vascular infusion of acetate and butyrate significantly increases colonic GLP-1 secretion, and to a minor extent also PYY secretion, but only after enhancement of intracellular cAMP. Propionate neither affected GLP-1 nor PYY secretion whether administered luminally or vascularly. A FFAR2- and FFAR3–specific agonist [( S)-2-(4-chlorophenyl)-3,3-dimethyl- N-(5-phenylthiazol-2-yl)butamide (CFMB)/ AR420626 ] had no effect on colonic GLP-1 output, and a FFAR3 antagonist ( AR399519 ) did not decrease the SCFA-induced GLP-1 response. However, the voltage-gated Ca2+-channel blocker nifedipine, the KATP-channel opener diazoxide, and the ATP synthesis inhibitor 2,4-dinitrophenol completely abolished the responses. FFAR2 receptor studies confirmed low-potent partial agonism of acetate, propionate, and butyrate, compared with CFMB, which is a full agonist with ~750-fold higher potency than the SCFAs. In conclusion, SCFAs may increase colonic GLP-1/PYY secretion, but FFAR2/FFAR3 do not seem to be involved. Rather, SCFAs are metabolized and appear to function as a colonocyte energy source.NEW & NOTEWORTHY By the use of in situ isolated perfused rat colon we show that short-chain fatty acids (SCFAs) primarily are used as a colonocyte energy source in the rat, subsequently triggering glucagon like peptide-1 (GLP-1) secretion independent of the free fatty acid receptors FFAR2 and FFAR3. Opposite many previous studies on SCFAs and FFAR2/FFAR3 and GLP-1 secretion, this experimental model allows investigation of the physiological interactions between luminal nutrients and secretion from cells whose function depend critically on their blood supply as well as nerve and paracrine interactions.

Effects of intraduodenal fatty acids on appetite, antropyloroduodenal motility, and plasma CCK and GLP-1 in humans vary with their chain length

2004 ◽  
Vol 287 (3) ◽  
pp. R524-R533 ◽  
Author(s):  
Kate L. Feltrin ◽  
Tanya J. Little ◽  
James H. Meyer ◽  
Michael Horowitz ◽  
Andre J. P. M. Smout ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Chain Length ◽  
Energy Intake ◽  
Decanoic Acid ◽  
Double Blind ◽  
Intraduodenal Infusion ◽  
Gut Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Intraduodenal Administration

The gastrointestinal effects of intraluminal fats may be critically dependent on the chain length of fatty acids released during lipolysis. We postulated that intraduodenal administration of lauric acid (12 carbon atoms; C12) would suppress appetite, modulate antropyloroduodenal pressure waves (PWs), and stimulate the release of cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) more than an identical dose of decanoic acid (10 carbon atoms; C10). Eight healthy males (19–47 yr old) were studied on three occasions in a double-blind, randomized fashion. Appetite perceptions, antropyloroduodenal PWs, and plasma CCK and GLP-1 concentrations were measured during a 90-min intraduodenal infusion of 1) C12, 2) C10, or 3) control (rate: 2 ml/min, 0.375 kcal/min for C12/C10). Energy intake at a buffet meal, immediately after completion of the infusion, was also quantified. C12, but not C10, suppressed appetite perceptions ( P < 0.001) and energy intake (control: 4,604 ± 464 kJ, C10: 4,109 ± 588 kJ, and C12: 1,747 ± 632 kJ; P < 0.001, C12 vs. control/C10). C12, but not C10, also induced nausea ( P < 0.001). C12 stimulated basal pyloric pressures and isolated pyloric PWs and suppressed antral and duodenal PWs compared with control ( P < 0.05 for all). C10 transiently stimulated isolated pyloric PWs ( P = 0.001) and had no effect on antral PWs but markedly stimulated duodenal PWs ( P = 0.004). C12 and C10 increased plasma CCK ( P < 0.001), but the effect of C12 was substantially greater ( P = 0.001); C12 stimulated GLP-1 ( P < 0.05), whereas C10 did not. In conclusion, there are major differences in the effects of intraduodenal C12 and C10, administered at 0.375 kcal/min, on appetite, energy intake, antropyloroduodenal PWs, and gut hormone release in humans.

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