Glucagon-like peptide-1 reduces contractile function and fails to boost glucose utilization in normal hearts in the presence of fatty acids

2013 ◽  
Vol 168 (4) ◽  
pp. 4085-4092 ◽  
Author(s):  
T. Dung Nguyen ◽  
Yasushige Shingu ◽  
Paulo A. Amorim ◽  
Michael Schwarzer ◽  
Torsten Doenst
Keyword(s):  
Fatty Acids ◽  
Glucose Utilization ◽  
Contractile Function ◽  
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

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.

scholarly journals Glucagon Like Peptide 1 and Evidence Around Diabetes Specific Nutrition

2019 ◽  
Vol 10 (2) ◽  
pp. 64-75
Author(s):  
ANSHU JOSHI ◽  
SAMEER RAO ◽  
GANESH KADHE
Keyword(s):  
Fatty Acids ◽  
Insulin Secretion ◽  
Gastric Emptying ◽  
Food Intake ◽  
Diabetes Management ◽  
Monounsaturated Fatty Acids ◽  
Complex Carbohydrate ◽  
Soluble Fibre ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

There has been significant research and development in pharmaco-therapeutic molecules for management of type 2 diabetes mellitus (T2DM). Diabetes specific nutrition intervention & newer incretin-based therapies have gained a lot of attention. Since incretins play an essential role in augmenting the post-prandial release of insulin, it is important to understand the science behind incretins and modulation of same by diabetic-specific nutrition (DSN). The purpose of this article is to summarize the available science around glucagon like peptide 1 (GLP-1) and the known role of nutrition, particularly diabetes specific nutrition. Literature published in PubMed, Google scholar and Embase were studied up to the end of August 2018. The key words of GLP-1, T2DM and Nutrients were used in different combinations. It was found that macronutrient aspects of DSN like complex carbohydrate, soluble fibre, proteins and high monounsaturated fatty acids augment GLP-1 secretion from intestinal L-cells. This may be attributed to insulin-trophic effects of DSN as well as its effects in causing deceleration in gastric emptying and reducing food intake. Hence, it was concluded that augmenting GLP-1 secretion in response to the intake of certain nutrients helps in modulating insulin secretion, metabolic homeostasis as well as decelerating gastric emptying and reducing food intake. DSN increases endogenous GLP-1 secretion which in turn improves insulin secretion and sensitivity. Thus, integrating DSN in mainstay diabetes management plans may result in better glycaemic and metabolic controls, particularly when GLP-1 based therapies are concurrently in use. Key Messages: DSN containing complex carbohydrate, soluble fibre, proteins and high monounsaturated fatty acids (MUFAs) augments GLP-1 secretion which in turn improves insulin secretion and sensitivity.

scholarly journals Loss of CASK Accelerates Heart Failure Development

2021 ◽  
Vol 128 (8) ◽  
pp. 1139-1155
Author(s):  
Julian Mustroph ◽  
Can M. Sag ◽  
Felix Bähr ◽  
Anna-Lena Schmidtmann ◽  
Shamindra N. Gupta ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sarcoplasmic Reticulum ◽  
Ventricular Arrhythmias ◽  
Contractile Function ◽  
Aortic Constriction ◽  
Functional Consequences ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Human And Mouse ◽  
Increased Susceptibility

Rationale: Increased myocardial activity of CaMKII (Ca/calmodulin-dependent kinase II) leads to heart failure and arrhythmias. In Drosophila neurons, interaction of CaMKII with CASK (Ca/CaM-dependent serine protein kinase) has been shown to inhibit CaMKII activity, but the consequences of this regulation for heart failure and ventricular arrhythmias are unknown. Objective: We hypothesize that CASK associates with CaMKII in human and mouse hearts thereby limiting CaMKII activity and that altering CASK expression in mice changes CaMKII activity accordingly, with functional consequences for contractile function and arrhythmias. Methods and Results: Immunoprecipitation revealed that CASK associates with CaMKII in human hearts. CASK expression is unaltered in heart failure but increased in patients with aortic stenosis. In mice, cardiomyocyte-specific knockout of CASK increased CaMKII-autophosphorylation at the stimulatory T287 site, but reduced phosphorylation at the inhibitory T305/306 site. Knockout of CASK mice showed increased CaMKII-dependent sarcoplasmic reticulum Ca leak, reduced sarcoplasmic reticulum Ca content, increased susceptibility to ventricular arrhythmias, greater loss of ejection fraction, and increased mortality after transverse aortic constriction. Intriguingly, stimulation of the cardiac glucagon-like peptide 1 receptor with exenatide increased CASK expression resulting in increased inhibitory CaMKII T305 phosphorylation, reduced CaMKII activity, and reduced sarcoplasmic reticulum Ca leak in wild type but not CASK-KO. Conclusions: CASK associates with CaMKII in the human heart. Knockout of CASK in mice increases CaMKII activity, leading to contractile dysfunction and arrhythmias. Increasing CASK expression reduces CaMKII activity, improves Ca handling and contractile function.

Effects of omega fatty acids on the short-term postprandial satiety related peptides in rats

2022 ◽  
Author(s):  
Hilal Hizli Guldemir ◽  
Nihal Buyukuslu ◽  
Pakize Yigit ◽  
Cagri Cakici ◽  
Ekrem Musa Ozdemir
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Peptide Yy ◽  
Insulin Response ◽  
Omega Fatty Acids ◽  
Oral Gavage ◽  
Short Term ◽  
Adult Rats ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract. We aimed to assess the effects of omega fatty acids on time depending on responses of satiety hormones. Sixty adult rats were randomly divided into 4 groups; linoleic acid (LA), α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) groups. For each fatty acid, the dose of 400 mg/kg was applied by oral gavage. Blood samples were taken after the 15, 30, 60 and 120 minutes. Ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), leptin and insulin hormones were analyzed by ELISA. We observed the significant increases (p<0.05) of the levels of CCK between n-3 (ALA, at 60th min; EPA, at 30th and 60th min and DHA, at 60 min) and n-6 (LA) supplemented rats. The highest GLP-1 levels were in ALA (0.70 ng/mL) and DHA (0.67 ng/mL) supplemented groups at 60th and 120th min indicating n-3 fatty acids efficiency on satiety compared to LA. It seems that ALA at 60th min and EPA at 120th min could provide the highest satiety effect with the highest insulin response, while the efficiency of LA supplementation on insulin-induced satiety diminished. The only significant change in AUC values among all hormones was in the CCK of the ALA group (p=0.004). The level of leptin increased in DHA and EPA supplemented rats (p=0.140). Our results showed that dietary omega fatty acids influenced the releasing of hormones in different ways possibly depending on chain length or saturation degree. Comprehensive studies need to be addressed for each fatty acid on satiety-related peptide hormones.

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