Chapter 4 Proteins, amino acids, and type 2 diabetes

2013 ◽  
pp. 89-114
Author(s):  
Yan Song ◽  
Simon Liu
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids

Dietary branched-chain amino acids intake exhibited a different relationship with type 2 diabetes and obesity risk: a meta-analysis

2018 ◽  
Vol 56 (2) ◽  
pp. 187-195 ◽  
Author(s):  
Akinkunmi Paul Okekunle ◽  
Meng Zhang ◽  
Zhen Wang ◽  
Justina Ucheojor Onwuka ◽  
Xiaoyan Wu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids ◽  
Meta Analysis ◽  
Branched Chain Amino Acids ◽  
Obesity Risk ◽  
Branched Chain ◽  
Diabetes And Obesity

scholarly journals Phenylalanine Impairs Insulin Signaling and Inhibits Glucose Uptake by Modifying IRβ

2021 ◽  
Author(s):  
Qian Zhou ◽  
Wan-Wan Sun ◽  
Jia-Cong Chen ◽  
Huilu Zhang ◽  
Jie Liu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Amino Acids ◽  
Insulin Receptor ◽  
Glucose Uptake ◽  
Insulin Signaling ◽  
Trna Synthetase ◽  
Blood Samples ◽  
Receptor Beta

Abstract Although elevated circulating amino acids are associated with the onset of type 2 diabetes (T2D), how amino acids act on cell insulin signaling and glucose uptake remains unclear. Herein, we report that phenylalanine modifies insulin receptor beta (IRβ) and inactivates insulin signaling and glucose uptake. Mice fed phenylalanine-rich chow or overexpressing human phenylalanyl-tRNA synthetase (hFARS) developed insulin resistance and symptoms of T2D. Mechanistically, FARS phenylalanylated lysine 1057/1079 of IRβ (F-K1057/1079) inactivated IRβ and prevented insulin from generating insulin signaling to promote glucose uptake by cells. SIRT1 reversed F-K1057/1079 and counteracted the insulin-inactivating effects of hFARS and phenylalanine. F-K1057/1079 and SIRT1 levels of white cells of T2D patients’ blood samples were positively and negatively correlated with T2D onset, respectively. Blocking F-K1057/1079 with phenylalaninol sensitized insulin signaling and relieved T2D symptoms in hFARS-transgenic and db/db mice. We revealed mechanisms of how phenylalanylation inactivates insulin signaling that may be employed to control T2D.

Abstract MP50: Metabolic Predictors of Type 2 Diabetes in American Indians: The Strong Heart Family Study

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Yun Zhu ◽  
Jiang He ◽  
Lyle G Best ◽  
Elisa T Lee ◽  
Barbara V Howard ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids ◽  
American Indians ◽  
Family Study ◽  
Fasting Glucose ◽  
Plasma Metabolites ◽  
Metabolic Alterations ◽  
Incident Cases ◽  
Strong Heart Family Study

Background: Type 2 diabetes (T2D) is characterized by profound metabolic abnormalities. Current glycemic indicators have limitations in identifying early metabolic alterations. Objective: To identify novel metabolic predictors of T2D in American Indians participating in the Strong Heart Family Study. Methods: Among 2,129 participants who had normal fasting glucose (NFG) at baseline (2001-2003) and also attended clinical examination after 5-year follow-up (2006-2009), 142 developed incident T2D, 514 developed incident impaired fasting glucose (IFG), and 1,473 remained to be NFG. The current analysis included all incident cases of T2D (n=142), 146 incident IFG (randomly selected from 514 participants with incident IFG) and 144 NFG (randomly selected from 1,473 participants with NFG at both visits). Baseline plasma metabolites were detected by high-resolution LC/MS. The prospective association of each metabolite with risk for T2D or IFG was investigated using weighted Cox’s hazard regression with frailty model, adjusting for sex, study center, age, BMI, renal function, fasting glucose and fasting insulin at baseline. Multiple testing was corrected by Bonferroni correction (significance level 2.8х10-6). Results: Thirty-nine metabolites from several major fuel sources, including sugar amino acids, amino acids, lipids, alkaloids, alkylamines, carboxylic acids, steroids, and aromatic homomonocylic/heteropolycyclic compounds, significantly predicted future risk of T2D (10 metabolites), or IFG (27 metabolites), or both (2 metabolites). Of these, N1,N12-diacetylspermine and betanidin, respectively, were the strongest predictors for increased (HR=4.59, 95% CI, 2.55-8.24, P=3.49х10-7) and decreased risk of T2D (HR=0.38, 95% CI, 0.28-0.52, P=4.64х10-10). The corresponding strongest predictors for IFG were hexanoic acid (HR=2.34, 95% CI, 1.84-2.98, P=3.15х10-12) and l-palmitoylcarnitine (HR=0.26, 95% CI, 0.18-0.37, P=1.14х10-13), respectively. Two metabolites, betanidin and dopamine, significantly predicted future onset of both T2D (HR=0.38, 95% CI, 0.28,0.52, P=4.64х10-10 for betanidin; HR=2.48, 95% CI, 1.71-3.58, P=1.42х10-6 for dopamine) and IFG (HR=0.52, 95% CI, 0.43,0.62, P=1.35х10-12 for betanidin; HR=2.24, 95% CI, 1.73,2.89, P=5.79х10-10 for dopamine). Multiple unknown compounds were also independently associated with risk of T2D, IFG or both. Conclusions: This study identifies both novel and known metabolic alterations associated with risk of diabetes in American Indians, an ethnic group suffering from disproportionately high rates of T2D. The incomplete overlapping of metabolic profiles between T2D and IFG highlights differential metabolic states of diabetes development. Our results not only provide novel insights in disease pathogenesis but also valuable data on potential new targets for risk prediction and treatment.

scholarly journals A High Level of Circulating Valine Is a Biomarker for Type 2 Diabetes and Associated with the Hypoglycemic Effect of Sitagliptin

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Xiaoyu Liao ◽  
Bingyao Liu ◽  
Hua Qu ◽  
LinLin Zhang ◽  
Yongling Lu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids ◽  
Aromatic Amino Acids ◽  
Gas Chromatography Mass Spectrometry ◽  
Glucose Levels ◽  
Increased Risk ◽  
Normal Glucose ◽  
Potential Strategy ◽  
High Level

Background. High levels of branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) were associated with an increased risk of hyperglycemia and the onset of diabetes. This study is aimed at assessing circulating valine concentrations in subjects with type 2 diabetes (T2D) and in T2D patients and high-fat diet- (HFD-) fed mice treated with the hypoglycemic agent sitagliptin (Sit) and analyzing the association of valine concentrations with metabolic parameters. Methods. Metabolomics in HFD-fed mice were analyzed by gas chromatography-mass spectrometry (GC-MS) systems. Plasma valine concentrations were detected with a commercial kit in 53 subjects with normal glucose levels (n=19), newly diagnosed T2D (n=20), placebo-treated T2D (n=7), or Sit-treated T2D (n=7). Biochemical parameters were also assessed in all participants. Results. Sit treatment markedly changed the pattern of amino acid in HFD-fed mice, especially by reducing the level of the BCAA valine. Compared with the healthy controls, the plasma valine concentrations were significantly higher in the T2D patients (p<0.05). Correlation analysis showed that the plasma valine concentration was positively correlated with the level of fasting plasma glucose (p<0.05). Moreover, the plasma valine concentrations were notably reduced after Sit treatment in T2D patients (p<0.05). Conclusions. Our findings demonstrate an important effect of Sit on the BCAA valine in T2D patients and HFD-fed mice, revealing a new hypoglycemic mechanism of it. Furthermore, the results suggest that the circulating valine level might be a novel biomarker for T2D and restoring the level of valine might be a potential strategy for diabetes therapy.

scholarly journals An In Vitro Model to Investigate the Role of Helicobacter pylori in Type 2 Diabetes, Obesity, Alzheimer’s Disease and Cardiometabolic Disease

2020 ◽  
Vol 21 (21) ◽  
pp. 8369
Author(s):  
Paola Cuomo ◽  
Marina Papaianni ◽  
Clementina Sansone ◽  
Antonio Iannelli ◽  
Domenico Iannelli ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids ◽  
Helicobacter Pylori ◽  
Bacterial Colonization ◽  
Mammalian Target Of Rapamycin ◽  
Disease Model ◽  
Cardiometabolic Disease ◽  
Isoleucine Leucine

Helicobacter pylori (Hp) is a Gram-negative bacterium colonizing the human stomach. Nuclear Magnetic Resonance (NMR) analysis of intracellular human gastric carcinoma cells (MKN-28) incubated with the Hp cell filtrate (Hpcf) displays high levels of amino acids, including the branched chain amino acids (BCAA) isoleucine, leucine, and valine. Polymerase chain reaction (PCR) Array Technology shows upregulation of mammalian Target Of Rapamycin Complex 1 (mTORC1), inflammation, and mitochondrial dysfunction. The review of literature indicates that these traits are common to type 2 diabetes, obesity, Alzheimer’s diseases, and cardiometabolic disease. Here, we demonstrate how Hp may modulate these traits. Hp induces high levels of amino acids, which, in turn, activate mTORC1, which is the complex regulating the metabolism of the host. A high level of BCAA and upregulation of mTORC1 are, thus, directly regulated by Hp. Furthermore, Hp modulates inflammation, which is functional to the persistence of chronic infection and the asymptomatic state of the host. Finally, in order to induce autophagy and sustain bacterial colonization of gastric mucosa, the Hp toxin VacA localizes within mitochondria, causing fragmentation of these organelles, depletion of ATP, and oxidative stress. In conclusion, our in vitro disease model replicates the main traits common to the above four diseases and shows how Hp may potentially manipulate them.

scholarly journals Serum acylcarnitines and amino acids and risk of type 2 diabetes in a multiethnic Asian population

2020 ◽  
Vol 8 (1) ◽  
pp. e001315
Author(s):  
Samuel H Gunther ◽  
Chin Meng Khoo ◽  
E-Shyong Tai ◽  
Xueling Sim ◽  
Jean-Paul Kovalik ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids ◽  
Risk Model ◽  
Characteristic Curve ◽  
Asian Population ◽  
Cox Proportional Hazards ◽  
Diabetes Risk ◽  
Study Program ◽  
Parental History

IntroductionWe evaluated whether concentrations of serum acylcarnitines and amino acids are associated with risk of type 2 diabetes and can improve predictive diabetes models in an Asian population.Research design and methodsWe used data from 3313 male and female participants from the Singapore Prospective Study Program cohort who were diabetes-free at baseline. The average age at baseline was 48.0 years (SD: 11.9 years), and participants were of Chinese, Malay, and Indian ethnicity. Diabetes cases were identified through self-reported physician diagnosis, fasting glucose and glycated hemoglobin concentrations, and linkage to national disease registries. We measured fasting serum concentrations of 45 acylcarnitines and 14 amino acids. The association between metabolites and incident diabetes was modeled using Cox proportional hazards regression with adjustment for age, sex, ethnicity, height, and parental history of diabetes, and correction for multiple testing. Metabolites were added to the Atherosclerosis Risk in Communities (ARIC) predictive diabetes risk model to assess whether they could increase the area under the receiver operating characteristic curve (AUC).ResultsParticipants were followed up for an average of 8.4 years (SD: 2.1 years), during which time 314 developed diabetes. Branched-chain amino acids (HR: 1.477 per SD; 95% CI 1.325 to 1.647) and the alanine to glycine ratio (HR: 1.572; 95% CI 1.426 to 1.733) were most strongly associated with diabetes risk. Additionally, the acylcarnitines C4 and C16-OH, and the amino acids alanine, combined glutamate/glutamine, ornithine, phenylalanine, proline, and tyrosine were significantly associated with higher diabetes risk, and the acylcarnitine C8-DC and amino acids glycine and serine with lower risk. Adding selected metabolites to the ARIC model resulted in a significant increase in AUC from 0.836 to 0.846.ConclusionsWe identified acylcarnitines and amino acids associated with risk of type 2 diabetes in an Asian population. A subset of these modestly improved the prediction of diabetes when added to an established diabetes risk model.

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