scholarly journals Hyperglucagonemia correlates with plasma levels of non-branched-chain amino acids in patients with liver disease independent of type 2 diabetes

2018 ◽  
Vol 314 (1) ◽  
pp. G91-G96 ◽  
Author(s):  
Nicolai J. Wewer Albrechtsen ◽  
Anders E. Junker ◽  
Mette Christensen ◽  
Sofie Hædersdal ◽  
Flemming Wibrand ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids ◽  
Liver Disease ◽  
Amino Acid ◽  
Plasma Levels ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Elevated Plasma ◽  
Total Amino Acids

Patients with type 2 diabetes (T2D) and patients with nonalcoholic fatty liver disease (NAFLD) frequently exhibit elevated plasma concentrations of glucagon (hyperglucagonemia). Hyperglucagonemia and α-cell hyperplasia may result from elevated levels of plasma amino acids when glucagon’s action on hepatic amino acid metabolism is disrupted. We therefore measured plasma levels of glucagon and individual amino acids in patients with and without biopsy-verified NAFLD and with and without type T2D. Fasting levels of amino acids and glucagon in plasma were measured, using validated ELISAs and high-performance liquid chromatography, in obese, middle-aged individuals with I) normal glucose tolerance (NGT) and NAFLD, II) T2D and NAFLD, III) T2D without liver disease, and IV) NGT and no liver disease. Elevated levels of total amino acids were observed in participants with NAFLD and NGT compared with NGT controls (1,310 ± 235 µM vs. 937 ± 281 µM, P = 0.03) and in T2D and NAFLD compared with T2D without liver disease (1,354 ± 329 µM vs. 511 ± 235 µM, P < 0.0001). Particularly amino acids with known glucagonotropic effects (e.g., glutamine) were increased. Plasma levels of total amino acids correlated to plasma levels of glucagon also when adjusting for body mass index (BMI), glycated hemoglobin (HbA1c), and cholesterol levels (β = 0.013 ± 0.007, P = 0.024). Elevated plasma levels of total amino acids associate with hyperglucagonemia in NAFLD patients independently of glycemic control, BMI or cholesterol - supporting the potential importance of a “liver-α-cell axis” in which glucagon regulates hepatic amino acid metabolism. Fasting hyperglucagonemia as seen in T2D may therefore represent impaired hepatic glucagon action with increasing amino acids levels. NEW & NOTEWORTHY Hypersecretion of glucagon (hyperglucagonemia) has been suggested to be linked to type 2 diabetes. Here, we show that levels of amino acids correlate with levels of glucagon. Hyperglucagonemia may depend on hepatic steatosis rather than type 2 diabetes.

Arabinoxylan Attenuates Type 2 Diabetes by Improvement of Carbohydrate, Lipid, and Amino Acid Metabolism

2018 ◽  
Vol 62 (20) ◽  
pp. 1800222 ◽  
Author(s):  
Qixing Nie ◽  
Haihong Chen ◽  
Jielun Hu ◽  
He Gao ◽  
Linlin Fan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism

Amino acid metabolism in the Zucker diabetic fatty rat: effects of insulin resistance and of type 2 diabetes

2004 ◽  
Vol 82 (7) ◽  
pp. 506-514 ◽  
Author(s):  
Enoka P Wijekoon ◽  
Craig Skinner ◽  
Margaret E Brosnan ◽  
John T Brosnan
Keyword(s):  
Insulin Resistance ◽  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Plasma Concentrations ◽  
Branched Chain Amino Acids ◽  
Insulin Resistant ◽  
Branched Chain

We investigated amino acid metabolism in the Zucker diabetic fatty (ZDF Gmi fa/fa) rat during the prediabetic insulin-resistant stage and the frank type 2 diabetic stage. Amino acids were measured in plasma, liver, and skeletal muscle, and the ratios of plasma/liver and plasma/skeletal muscle were calculated. At the insulin-resistant stage, the plasma concentrations of the gluconeogenic amino acids aspartate, serine, glutamine, glycine, and histidine were decreased in the ZDF Gmi fa/fa rats, whereas taurine, α-aminoadipic acid, methionine, phenylalanine, tryptophan, and the 3 branched-chain amino acids were significantly increased. At the diabetic stage, a larger number of gluconeogenic amino acids had decreased plasma concentrations. The 3 branched-chain amino acids had elevated plasma concentrations. In the liver and the skeletal muscles, concentrations of many of the gluconeogenic amino acids were lower at both stages, whereas the levels of 1 or all of the branched-chain amino acids were elevated. These changes in amino acid concentrations are similar to changes seen in type 1 diabetes. It is evident that insulin resistance alone is capable of bringing about many of the changes in amino acid metabolism observed in type 2 diabetes.Key words: plasma amino acids, liver amino acids, muscle amino acids, gluconeogenesis.

Quantitative metabolomic and lipidomic profiling reveals aberrant amino acid metabolism in type 2 diabetes

2013 ◽  
Vol 9 (2) ◽  
pp. 307-317 ◽  
Author(s):  
Prabhjit Kaur ◽  
Nasser Rizk ◽  
Sereen Ibrahim ◽  
Yue Luo ◽  
Noura Younes ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism

Zanthoxylum alkylamides improve amino acid metabolism in type 2 diabetes mellitus rats

2020 ◽  
Vol 44 (10) ◽  
Author(s):  
Xunyu Wei ◽  
Bing Yang ◽  
Guangjing Chen ◽  
Di Wang ◽  
Yue Shi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism

scholarly journals Associations of network-derived metabolite clusters with prevalent type 2 diabetes among adults of Puerto Rican descent

2021 ◽  
Vol 9 (1) ◽  
pp. e002298
Author(s):  
Danielle E Haslam ◽  
Liming Liang ◽  
Dong D Wang ◽  
Rachel S Kelly ◽  
Clemens Wittenbecher ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acid ◽  
Puerto Rican ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Meta Analysis ◽  
Random Effect ◽  
Plasma Metabolites ◽  
Blood Draw

IntroductionWe investigated whether network analysis revealed clusters of coregulated metabolites associated with prevalent type 2 diabetes (T2D) among Puerto Rican adults.Research design and methodsWe used liquid chromatography-mass spectrometry to measure fasting plasma metabolites (>600) among participants aged 40–75 years in the Boston Puerto Rican Health Study (BPRHS; discovery) and San Juan Overweight Adult Longitudinal Study (SOALS; replication), with (n=357; n=77) and without (n=322; n=934) T2D, respectively. Among BPRHS participants, we used unsupervised partial correlation network-based methods to identify and calculate metabolite cluster scores. Logistic regression was used to assess cross-sectional associations between metabolite clusters and prevalent T2D at the baseline blood draw in the BPRHS, and significant associations were replicated in SOALS. Inverse-variance weighted random-effect meta-analysis was used to combine cohort-specific estimates.ResultsSix metabolite clusters were significantly associated with prevalent T2D in the BPRHS and replicated in SOALS (false discovery rate (FDR) <0.05). In a meta-analysis of the two cohorts, the OR and 95% CI (per 1 SD increase in cluster score) for prevalent T2D were as follows for clusters characterized primarily by glucose transport (0.21 (0.16 to 0.30); FDR <0.0001), sphingolipids (0.40 (0.29 to 0.53); FDR <0.0001), acyl cholines (0.35 (0.22 to 0.56); FDR <0.0001), sugar metabolism (2.28 (1.68 to 3.09); FDR <0.0001), branched-chain and aromatic amino acids (2.22 (1.60 to 3.08); FDR <0.0001), and fatty acid biosynthesis (1.54 (1.29 to 1.85); FDR <0.0001). Three additional clusters characterized by amino acid metabolism, cell membrane components, and aromatic amino acid metabolism displayed significant associations with prevalent T2D in the BPRHS, but these associations were not replicated in SOALS.ConclusionsAmong Puerto Rican adults, we identified several known and novel metabolite clusters that associated with prevalent T2D.

Beyond lipids, pharmacological PPARα activation has important effects on amino acid metabolism as studied in the rat

2007 ◽  
Vol 292 (4) ◽  
pp. E1157-E1165 ◽  
Author(s):  
Kashif Sheikh ◽  
Germán Camejo ◽  
Boel Lanne ◽  
Torbjörn Halvarsson ◽  
Marie Rydén Landergren ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Plasma Levels ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Body Weight Gain ◽  
Saturated Fat ◽  
Whole Body ◽  
Dna Arrays ◽  
Plasma Urea

PPARα agonists have been characterized largely in terms of their effects on lipids and glucose metabolism, whereas little has been reported about effects on amino acid metabolism. We studied responses to the PPARα agonist WY 14,643 (30 μmol·kg−1·day−1 for 4 wk) in rats fed a saturated fat diet. Plasma and urine were analyzed with proton NMR. Plasma amino acids were measured using HPLC, and hepatic gene expression was assessed with DNA arrays. The high-fat diet elevated plasma levels of insulin and triglycerides (TG), and WY 14,643 treatment ameliorated this insulin resistance and dyslipidemia, lowering plasma insulin and TG levels. In addition, treatment decreased body weight gain, without altering cumulative food intake, and increased liver mass. WY 14,643 increased plasma levels of 12 of 22 amino acids, including glucogenic and some ketogenic amino acids, whereas arginine was significantly decreased. There was no alteration in branched-chain amino acid levels. Compared with the fat-fed control animals, WY 14,643-treated animals had raised plasma urea and ammonia levels as well as raised urine levels of N-methylnicotinamide and dimethylglycine. WY 14,643 induced changes in a number of key genes involved in amino acid metabolism in addition to expected effects on hepatic genes involved in lipid catabolism and ketone body formation. In conclusion, the present results suggest that, in rodents, effects of pharmacological PPARα activation extend beyond control of lipid metabolism to include important effects on whole body amino acid mobilization and hepatic amino acid metabolism.

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