Effect of diabetes on the concentration of amino acids in plasma and heart muscle of rats.
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ABSTRACT:
SUBMITTER: Scharff R
PROVIDER: S-EPMC1264973 | biostudies-other | 1966 Apr
REPOSITORIES: biostudies-other
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Project description:1. Rat heart perfused with Krebs-Henseleit bicarbonate buffer released material containing ninhydrin-positive nitrogen, but the amount was less than that reported to be released by diaphragm; glucose, but not insulin, decreased the release of ninhydrin-positive nitrogen and increased the concentration of the same material in the intracellular water of heart. 2. When heart was perfused with a mixture of amino acids and glucose, there was actually a net uptake, and an increase in intracellular concentration, of ninhydrin-positive nitrogen. Changes in the concentration of ninhydrin-positive nitrogen did not accurately reflect changes in concentration of amino acids. 3. The effect of insulin on the actual concentration of individual amino acids in heart muscle was examined by perfusing the heart with a mixture of amino acids and other ninhydrin-positive substances in the same concentration as they are found in plasma. 4. The effect of insulin on the concentrations of amino acids in the medium and in the intracellular water of the heart was determined after perfusion for different periods of time. No clear or meaningful effect of insulin was observed, despite the fact that insulin significantly increased the accumulation, in each of the same hearts, of radioactivity from amino[(14)C]isobutyric acid.
| S-EPMC1264570 | biostudies-other
Project description:BackgroundEpoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid with multiple biological functions. Rodent experiments suggest EETs play a role in insulin sensitivity and diabetes, but evidence in humans is limited. To address this knowledge gap, we conducted a case-cohort study in the Strong Heart Family Study, a prospective cohort among American Indians.MethodsWe measured 4 EET species and 4 species of corresponding downstream metabolites, dihydroxyeicosatrieonic acids (DHETs), in plasma samples from 1161 participants, including 310 with type 2 diabetes. We estimated the associations of total (esterified and free) EETs and DHETs with incident diabetes risk, adjusting for known risk factors. We also examined cross-sectional associations with plasma fasting insulin and glucose in the case-cohort and in 271 participants without diabetes from the older Strong Heart Study cohort, and meta-analyzed the results from the 2 cohorts.FindingsWe observed no significant association of total EET or DHET levels with incident diabetes. In addition, plasma EETs were not associated with plasma insulin or plasma glucose. However, higher plasma 14,15-DHET was associated with lower plasma insulin and lower plasma glucose.InterpretationIn this first prospective study of EETs and diabetes, we found no evidence for a role of total plasma EETs in diabetes. The novel associations of 14,15-DHET with insulin and glucose warrant replication and exploration of possible mechanisms.FundingUS National Institutes of Health.
| S-EPMC8010619 | biostudies-literature
Project description:ContextAmino acids (AAs) and their metabolites are altered with obesity and may be predictive of future diabetes in adults, but there are fewer studies on AAs, as well as conflicting findings on how they vary with obesity, in adolescents.ObjectiveTo determine whether plasma AAs vary with body composition and insulin sensitivity and are altered in response to exercise training.DesignCross-sectional, and an exercise intervention.SettingTribal wellness center.ParticipantsAmerican Indian boys and girls, 11 to 17 years of age with obesity (Ob, n = 58) or normal weight (NW, n = 36).InterventionThe Ob group completed 16 weeks of aerobic exercise training.Main outcome measureA panel of 42 plasma AAs.ResultsCompared with the NW group, the Ob group had lower aerobic fitness and insulin sensitivity (interactive homeostasis model assessment 2), 17 AAs that were higher, and 7 AAs that were lower. Branched-chain AAs (+10% to 16%), aromatic AAs (+15% to 32%), and glutamate were among the higher AAs; all were positively correlated with body fat and negatively correlated with insulin sensitivity. The lysine metabolite 2-aminoadipic acid (2-AAA) and the valine metabolite β-aminoisobutyric acid (BAIBA) were 47% higher and 29% lower, respectively, in the Ob group, and were positively (2-AAA) and negatively (BAIBA) correlated with insulin sensitivity. Exercise training increased aerobic fitness by 10%, but body composition, insulin sensitivity, and AAs were not significantly changed.ConclusionsSeveral plasma AAs are altered in American Indian adolescents with obesity and are associated with insulin sensitivity, but they were not altered with this exercise intervention.
| S-EPMC6584131 | biostudies-literature
Project description:1. Rat heart was perfused with a mixture of amino acids and other ninhydrin-positive substances in the same concentrations as they are found in plasma, and with or without sufficient puromycin to suppress protein synthesis all but completely. 2. In the presence of puromycin, but not in its absence, insulin increased the concentrations of most of the individual amino acids in the intracellular water of heart. 3. The results accord with the conclusion that insulin increases the entry of most, if not all, amino acids into muscle.
| S-EPMC1264571 | biostudies-other
Project description:BackgroundPlasma branched-chain amino acids (BCAA) levels are predictors of glycometabolic disorders, leading to diabetes. Microbes, including periodontal pathogens, are thought to be associated with elevated plasma BCAA levels. This study aimed to evaluate the relationship between salivary occult blood (SOB) and plasma BCAA levels in middle-aged Japanese individuals.MethodsSixty-four Japanese individuals aged ≥ 40 years were recruited for this study, which was conducted in Fukuoka Prefecture, Japan, from August to December 2021. Individuals diagnosed with and/or treated for diabetes were excluded from the study. The body mass index (BMI); plasma concentrations of total, high-density, and low-density lipoprotein cholesterol; triglyceride, glucose, and BCAA; and glycosylated hemoglobin ratio were measured. A basic periodontal examination was performed after the SOB test.ResultsThe median age of participants (men-20; women-44) was 55 (range, 41-78) years. The plasma BCAA concentration in the SOB-positive group (477 [400-658] μmol/L) was higher than that in the SOB-negative group (432 [307-665] μmol/L). Linear regression analysis revealed that SOB remained independently associated with the plasma BCAA level with statistical significance (β = 0.17, p = 0.02) after adjusting for sex, age, and BMI.ConclusionsSOB was positively correlated with plasma BCAA levels in middle-aged Japanese individuals. Thus, SOB may be a predictor of elevated plasma BCAA levels.
| S-EPMC9332040 | biostudies-literature
Project description:Obesity is associated with mitochondrial dysfunction in skeletal muscle. Increasing the plasma amino acid (AA) concentrations stimulates mitochondrial adenosine triphosphate (ATP) production in lean individuals.To determine whether acute elevation in plasma AAs enhances muscle mitochondrial respiration and ATP production in subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria in obese adults.Assessment of SS and IMF mitochondrial function during saline (i.e., control) and AA infusions.Eligible participants were healthy lean (body mass index, <25 kg/m2; age, 37 ± 3 years; n = 10) and obese (body mass index >30 kg/m2; age 35 ± 3 years; n = 11) subjects.Single trial of saline infusion followed by AA infusion. SS and IMF mitochondria were isolated from muscle biopsies collected at the end of the saline and AA infusions.Mitochondrial respiration and ATP production.AA infusion increased adenosine 5'-diphosphate (ADP)-stimulated respiration and ATP production rates of SS mitochondria in the lean (P < 0.05), but not obese, subjects. Furthermore, AA infusion increased the uncoupled (i.e., non-ADP-stimulated) respiration of SS mitochondria in the lean subjects only (P < 0.05). AA infusion had no effect on any of these parameters in IMF mitochondria in either lean or obese subjects (P > 0.05).Increasing the plasma AA concentrations enhances the capacity for respiration and ATP production of muscle SS, but not IMF, mitochondria in lean individuals, in parallel with increases in uncoupled respiration. However, neither of these parameters increases in muscle SS or IMF mitochondria in obese individuals.
| S-EPMC5718694 | biostudies-literature
Project description:Previous studies have consistently reported an association between circulating levels of branched-chain amino acids (BCAAs) or adipokines and insulin resistance; however, the association between BCAA and adipokine levels remains to be clarified. In this cross-sectional study involving 678 participants (435 men) without diabetes, plasma BCAA (valine, leucine, and isoleucine), adipokine (total and high molecular weight [HMW] adiponectin, leptin, and tumor necrosis factor-? [TNF-?]) concentrations, and an updated homeostasis model assessment of insulin resistance (HOMA2-IR) were measured. The association between the concentrations of total BCAAs and adipokines was adjusted for confounding factors, including body mass index. For the lowest and highest BCAA quartiles, the adjusted geometric mean levels of HMW adiponectin were, respectively, 1.51 and 0.91??g/mL, in men (P for trend?<?0.0001); 3.61 and 2.29??g/mL, in women (P?=?0.0005). The corresponding geometric mean levels for leptin were 1681 and 2620?pg/mL, in men (P?=?0.003), and 4270 and 6510?pg/mL, in women (P?=?0.003). Those for HOMA2-IR were 0.89 and 1.11, in men (P?<?0.0001), and 0.79 and 0.96, in women (P?<?0.0001); no significant association was found with TNF-?. These results suggest significant associations between BCAA concentrations and those for adiponectin, leptin and HOMA2-IR in individuals without diabetes.
| S-EPMC5773488 | biostudies-literature
Project description:ObjectivesThis study aimed to explore associations between plasma free amino acids (PFAA) and risk of cardiovascular disease (CVD) in Chinese with Type 2 diabetes (T2D).MethodsWe retrieved 741 inpatients with T2D consecutively from tertiary hospital. Twenty-three PFAA were measured. CVD was defined as having coronary heart disease (CHD) or stroke. Principal component analysis was used to extract factors of PFAA. Factors and their components were introduced into binary logistic regressions as continuous and tertiles to obtain OR (odds ratio) and 95% confidence interval (CI) for CVD (or its components) risk.ResultsOf 741 inpatients, 282 (38.1%) had CVD (CHD alone: 122, stroke alone: 109, both: 51). Five factors were extracted, accounting for 65% of the total variance. Factor 3 composed of glutamate and tryptophan was associated with increased CVD risk (ORs, 95%CI of top vs. bottom tertiles: 1.60, 1.02-2.50 for CVD; 2.19, 1.17-4.07 for stroke, 1.51, 0.83-2.73 for CHD); the ORs (top vs. bottom tertiles) of glutamate were 2.62 (95%CI, 1.18-5.84) for stroke and 1.44 (0.80-2.61) for CHD; the ORs (top vs. bottom tertiles) of tryptophan were 1.50 (0.81-2.75) for stroke and 1.07 (0.58-1.97) for CHD. Comparable results were observed according to important confounders (all P for interaction >0.05).ConclusionsElevated factor 3 composed of glutamate and tryptophan was associated with increased CVD, especially stroke in T2D in China.
| S-EPMC8081348 | biostudies-literature
Project description:INTRODUCTION:The global prevalence of type 2 diabetes (T2D) is increasing rapidly, especially in low- and middle-income countries and has a high number of associated comorbidities. Plasmatic concentrations of branched chain amino acids (BCAA) and retinol-binding protein 4 (RBP4) have been shown to be elevated in T2D subjects in cross-sectional studies. However, the effect of lifestyle community-based interventions on BCAA and RBP4 concentrations has not yet been analyzed. MATERIAL AND METHODS:The Feel4Diabetes study is a school and community-based intervention that identified 360 European families with a high risk of developing T2D according to the FINDRISC questionnaire. Families were randomized in control and intervention groups were followed-up from 2016 to 2018. In the Spanish families, the concentration of BCAA and RBP4 was determined in 266 subjects (115 control and 151 intervention group) that attended the three time-point assessments by colorimetric and ELISA reaction, respectively. RESULTS:Baseline BCAA levels showed positive correlations with the FINDRISC score and glucose impairment (baseline glucose, insulin, and glycated hemoglobin), body mass index, and body weight. The participants receiving the community-based intervention showed a significant decrease in glycated hemoglobin and BCAA levels compared to the control group (p = 0.011 and p < 0.001, respectively). However, baseline RBP4 did not show significant correlations with anthropometric and glycemic parameters, and no significant change was observed in anthropometric parameters and RBP4 concentrations throughout the follow-up. CONCLUSION:A community-based intervention on lifestyle led to a significant reduction in BCAA levels regardless of weight loss. These findings suggest that this interventional approach could be promising in T2D prevention.
| S-EPMC7140606 | biostudies-literature
Project description:In the present study, the BCAAs (branched-chain amino acids) leucine and valine caused a significant suppression in the loss of body weight in mice bearing a cachexia-inducing tumour (MAC16), producing a significant increase in skeletal muscle wet weight, through an increase in protein synthesis and a decrease in degradation. Leucine attenuated the increased phosphorylation of PKR (double-stranded-RNA-dependent protein kinase) and eIF2alpha (eukaryotic initiation factor 2alpha) in skeletal muscle of mice bearing the MAC16 tumour, due to an increased expression of PP1 (protein phosphatase 1). Weight loss in mice bearing the MAC16 tumour was associated with an increased amount of eIF4E bound to its binding protein 4E-BP1 (eIF4E-binding protein 1), and a progressive decrease in the active eIF4G-eIF4E complex due to hypophosphorylation of 4E-BP1. This may be due to a reduction in the phosphorylation of mTOR (mammalian target of rapamycin), which may also be responsible for the decreased phosphorylation of p70(S6k) (70 kDa ribosomal S6 kinase). There was also a 5-fold increase in the phosphorylation of eEF2 (eukaryotic elongation factor 2), which would also decrease protein synthesis through a decrease in translation elongation. Treatment with leucine increased phosphorylation of mTOR and p70(S6k), caused hyperphosphorylation of 4E-BP1, reduced the amount of 4E-BP1 associated with eIF4E and caused an increase in the eIF4G-eIF4E complex, together with a reduction in phosphorylation of eEF2. These changes would be expected to increase protein synthesis, whereas a reduction in the activation of PKR would be expected to attenuate the increased protein degradation.
| S-EPMC2267397 | biostudies-other