scholarly journals Type-2-diabetes Alters CSF but not Plasma Metabolomic and AD Risk Profiles in Vervet Monkeys

2019 ◽  
Author(s):  
Kylie Kavanagh ◽  
Stephen M. Day ◽  
Morgan C. Pait ◽  
William R. Mortiz ◽  
Christopher B. Newgard ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids ◽  
Cerebral Metabolism ◽  
Vervet Monkeys ◽  
Plasma Lactate ◽  
Glucose Levels ◽  
Highly Correlated ◽  
Lactate Levels ◽  
The Brain

AbstractEpidemiological studies suggest that individuals with type 2 diabetes (T2D) have a 2-4 fold increased risk for developing Alzheimer’s disease (AD), however the exact mechanisms linking the two disease is unknown. In both conditions, the majority of pathophysiological changes (including glucose and insulin dysregulation, insulin resistance, and AD-related changes in Aβ and tau) occur decades before the onset of clinical symptoms and diagnosis. In this study, we investigated the relationship between metabolic biomarkers associated with T2D and AD-related pathology, including Aβ levels, from cerebrospinal fluid (CSF) and fasting plasma of healthy, prediabetic (PreD), and T2D vervet monkeys (Chlorocebus aethiops sabeus). Consistent with the human disease, T2D monkeys have increased plasma and CSF glucose levels as they transition from normoglycemia to pre-diabetic and diabetic states. Although plasma levels of acylcarnitines and amino acids remained largely unchanged, peripheral hyperglycemia correlated with decreased CSF acylcarnitines and CSF amino acids, including branched chain amino acid (BCAA) concentrations, suggesting profound changes in cerebral metabolism coincident with systemic glucose dysregulation. Moreover, CSF Aβ40 and CSF Aβ42 levels decreased in T2D monkeys, a phenomenon observed in the human course of AD which coincides with increased amyloid deposition within the brain. In agreement with our previous studies in mice, CSF Aβ40 and CSF Aβ42 were highly correlated with CSF glucose levels, suggesting that glucose levels in the brain are associated with changes in Aβ metabolism. Interestingly, CSF Aβ40 and CSF Aβ42 levels were also highly correlated with plasma but not CSF lactate levels, suggesting that plasma lactate might serve as a potential biomarker of disease progression in AD. Moreover, CSF glucose and plasma lactate levels were correlated with CSF amino acid and acylcarnitine levels, demonstrating alterations in cerebral metabolism occurring with the onset of T2D. Together, these data suggest that peripheral metabolic changes associated with the development of T2D produce alterations in brain metabolism that lead to early changes in the amyloid cascade, similar to those observed in pre-symptomatic AD.

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 The Gonadal Hormone Regulates the Plasma Lactate Levels in Type 2 Diabetes Treated With and Without Metformin

2012 ◽  
Vol 14 (6) ◽  
pp. 469-474 ◽  
Author(s):  
Ying Shen ◽  
Fang Liu ◽  
Qing Li ◽  
Junling Tang ◽  
Taishan Zheng ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gonadal Hormone ◽  
Plasma Lactate ◽  
Lactate Levels

scholarly journals Gut-Microbial Metabolites, Probiotics and Their Roles in Type 2 Diabetes

2021 ◽  
Vol 22 (23) ◽  
pp. 12846
Author(s):  
Lixiang Zhai ◽  
Jiayan Wu ◽  
Yan Y. Lam ◽  
Hiu Yee Kwan ◽  
Zhao-xiang Bian ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids ◽  
Gut Microbiota ◽  
Aromatic Amino Acids ◽  
Microbial Metabolites ◽  
High Blood Glucose ◽  
Gaseous Products ◽  
Glucose Levels ◽  
Novel Therapeutic Strategies

Type 2 diabetes (T2D) is a worldwide prevalent metabolic disorder defined by high blood glucose levels due to insulin resistance (IR) and impaired insulin secretion. Understanding the mechanism of insulin action is of great importance to the continuing development of novel therapeutic strategies for the treatment of T2D. Disturbances of gut microbiota have been widely found in T2D patients and contribute to the development of IR. In the present article, we reviewed the pathological role of gut microbial metabolites including gaseous products, branched-chain amino acids (BCAAs) products, aromatic amino acids (AAAs) products, bile acids (BA) products, choline products and bacterial toxins in regulating insulin sensitivity in T2D. Following that, we summarized probiotics-based therapeutic strategy for the treatment of T2D with a focus on modulating gut microbiota in both animal and human studies. These results indicate that gut-microbial metabolites are involved in the pathogenesis of T2D and supplementation of probiotics could be beneficial to alleviate IR in T2D via modulation of gut microbiota.

Lactate Reverses Insulin-Induced Hypoglycemic Stupor in Suckling—Weanling Mice: Biochemical Correlates in Blood, Liver, and Brain

1983 ◽  
Vol 3 (4) ◽  
pp. 498-506 ◽  
Author(s):  
Jean Holowach Thurston ◽  
Richard E. Hauhart ◽  
James A. Schiro
Keyword(s):  
Amino Acids ◽  
Citric Acid ◽  
Energy Metabolism ◽  
Citric Acid Cycle ◽  
Plasma Lactate ◽  
Brain Glucose ◽  
Acid Cycle ◽  
Glucose Levels ◽  
Glycolytic Intermediates ◽  
Lactate Levels

The recovery of weanling mice from insulin-induced hypoglycemic stupor–coma after injection of sodium -l(+)-lactate (18 mmol/kg) was as rapid (10 min) as in litter-mates treated with glucose (9 mmol/kg). Stimulated by this dramatic action, we studied the effects of lactate injection on brain carbohydrate and energy metabolism in normal and hypoglycemic mice; blood and liver tissue were also studied. Ten minutes after lactate injection in normal mice, plasma lactate levels increased by 15 mmol/L; plasma glucose levels were unchanged, but the β-hydroxybutyrate concentration fell 59%. In the brains of these animals, glucose levels increased 2.3-fold, and there were significant increases in brain glycogen (10%), glucose-6-phosphate (27%), lactate (68%), pyruvate (37%), citrate (12%), and malate (19%); the increase in α-ketoglutarate (32%) was not significant. Lactate injection reduced the cerebral glucose-use rate 40%. These changes were not due to lactate-induced increases in blood [HCO−3] and pH (examined by injection of 15 mmol/kg sodium bicarbonate). Although lactate injection of hypoglycemic mice doubled levels of glucose in plasma and brain (not significant) and most of the cerebral glycolytic intermediates, values were far below normal (still in the range seen in hypoglycemic animals). By contrast, citrate and α-ketoglutarate levels returned to normal; the large increase in malate was not significant. Reduced glutamate levels increased to normal, and elevated aspartate levels fell below normal. Thus, recovery from hypoglycemic stupor does not necessarily depend on normal levels of plasma and/or brain glucose (or glycolytic intermediates). Near normal levels of the Krebs citric acid cycle intermediates suggest that changes in these metabolites, amino acids, or derived substrates relate to the dramatic recovery of hypoglycemic mice after lactate injection.

Effect of High ß-Glucan Barley on Postprandial Plasma Glucose Levels in Subjects with Normal Glucose Tolerance and Patients with Type 2 Diabetes

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 772-P
Author(s):  
MARIKO HIGA ◽  
AYANA HASHIMOTO ◽  
MOE HAYASAKA ◽  
MAI HIJIKATA ◽  
AYAMI UEDA ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Tolerance ◽  
Plasma Glucose ◽  
Normal Glucose Tolerance ◽  
Postprandial Plasma Glucose ◽  
Glucose Levels ◽  
Normal Glucose

Efeitos dos Programas de Treinamento Aeróbio, de Força e Combinado na Glicose Sanguínea em Diabéticos do Tipo 2: uma Revisão Sistemática/ Effects of Aerobic, Strength and Combined Programs Training on Blood Glucose in Type 2 Diabetic: a Systematic Review.

1970 ◽  
Vol 5 (1) ◽  
pp. 61-74 ◽  
Author(s):  
Alexandre de Souza E Silva ◽  
Maria Paula Gonçalves Mota
Keyword(s):  
Diabetes Mellitus ◽  
Systematic Review ◽  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Training Program ◽  
Aerobic Training ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Pubmed Database

O trabalho tem como objetivo analisar os estudos que avaliaram os efeitos dos programas de treinamento aeróbio, força e combinado nos níveis de glicose sanguínea em indivíduos com diabetes do tipo 2. Foi utilizado o método de revisão sistemática, sendo utilizada a base de dados PubMed. As palavras chaves utilizadas para pesquisa foram training and diabetes. Foram identificados 484 artigos originais. Apenas 17 estudos respeitaram os critérios de inclusão. Os resultados evidenciam que os programas de treinamento aeróbio diminuíram os níveis de glicose. O programa de treinamento de força também foi favorável à diminuição dos níveis de glicose sanguínea. Já o programa de treinamento combinado não demonstrou efeitos favoráveis no controle da glicose sanguínea. Conclui-se que o programa de treinamento aeróbio e de força ajudam a controlar os níveis de glicose sanguínea em indivíduos com diabetes do tipo 2. Palavras-chave: diabetes mellitus, treinamento, glicose.ABSTRACTThe study aims to analyze the studies that evaluated the effects of aerobic, strength and combined programs training in blood glucose levels in people with type 2 diabetes. We used a systematic review method and is used to PubMed database. The key words used for searching were training and diabetes. We identified 484 original articles. Only 17 studies complied with the inclusion criteria. The results show that aerobic training programs decreased glucose levels. The strength training program was also favorable to decrease in blood glucose levels. But the combined training program has not shown favorable effects on blood glucose control. We conclude that the aerobic training and strength helps control blood glucose levels in individuals with type 2 diabetes. Keywords: diabetes mellitus, training, glucose.

scholarly journals The frequency of Tim-3 on circulating Tfh cells was increased in type 2 diabetes mellitus patients

2020 ◽  
Vol 18 ◽  
pp. 205873922098280
Author(s):  
Shuai Guo ◽  
Xujie Yu ◽  
Limei Wang ◽  
Jing Jing ◽  
Yuanyuan Sun ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
High Glucose ◽  
C Peptide ◽  
Glucose Levels ◽  
Tfh Cells ◽  
Fasting Plasma ◽  
Healthy Donors

Type 2 diabetes mellitus (T2DM) is a chronic, low-grade inflammation disease. T follicular helper (Tfh) cells and T cell immunoglobulin and mucin domain 3 (Tim-3) are implicated in many immune diseases. This study aims to explore whether Tim-3 expression on Tfh cells is associated with T2DM progression. White blood cells (WBCs) were harvested from 30 patients with T2DM and 20 healthy donors. The abundance of circulating Tfh cells (cTfh) and the frequency of Tim-3 were analyzed by flow cytometry. Levels of fasting plasma glucose (FPG), insulin, hemoglobin A1C (HbA1C), and fasting plasma C-peptide were measured. Body mass index (BMI) and diabetes duration were also recorded. Patients with T2DM had higher numbers of cTfh cells. In addition, cTfh cells showed a negative correlation with HbA1C and diabetes duration, a positive correlation with fasting plasma C-peptide. The frequency of Tim-3 on cTfh cells was higher among T2DM patients compared with healthy donors. The in vitro experiment showed that high glucose levels increased the abundance cTfh cells but had no effect on Tim-3 expression. Our results suggest that cTfh cells and associated Tim-3 frequency may contribute to the progression of T2DM, and high glucose levels may influence cTfh cells directly.

scholarly journals Synergistic Effects of Milk-Derived Exosomes and Galactose on α-Synuclein Pathology in Parkinson’s Disease and Type 2 Diabetes Mellitus

2021 ◽  
Vol 22 (3) ◽  
pp. 1059
Author(s):  
Bodo C. Melnik
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Dopaminergic Neurons ◽  
Vagal Nerve ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
The Brain

Epidemiological studies associate milk consumption with an increased risk of Parkinson’s disease (PD) and type 2 diabetes mellitus (T2D). PD is an α-synucleinopathy associated with mitochondrial dysfunction, oxidative stress, deficient lysosomal clearance of α-synuclein (α-syn) and aggregation of misfolded α-syn. In T2D, α-syn promotes co-aggregation with islet amyloid polypeptide in pancreatic β-cells. Prion-like vagal nerve-mediated propagation of exosomal α-syn from the gut to the brain and pancreatic islets apparently link both pathologies. Exosomes are critical transmitters of α-syn from cell to cell especially under conditions of compromised autophagy. This review provides translational evidence that milk exosomes (MEX) disturb α-syn homeostasis. MEX are taken up by intestinal epithelial cells and accumulate in the brain after oral administration to mice. The potential uptake of MEX miRNA-148a and miRNA-21 by enteroendocrine cells in the gut, dopaminergic neurons in substantia nigra and pancreatic β-cells may enhance miRNA-148a/DNMT1-dependent overexpression of α-syn and impair miRNA-148a/PPARGC1A- and miRNA-21/LAMP2A-dependent autophagy driving both diseases. MiRNA-148a- and galactose-induced mitochondrial oxidative stress activate c-Abl-mediated aggregation of α-syn which is exported by exosome release. Via the vagal nerve and/or systemic exosomes, toxic α-syn may spread to dopaminergic neurons and pancreatic β-cells linking the pathogenesis of PD and T2D.

scholarly journals Pharmaceutical hit of anti type 2 Diabetes mellitus on the phenolic extract of Malaka (Phyllanthus emblica L.) flesh

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Musri Musman ◽  
Mauli Zakia ◽  
Ratu Fazlia Inda Rahmayani ◽  
Erlidawati Erlidawati ◽  
Safrida Safrida
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Body Weight ◽  
Blood Glucose ◽  
Phyllanthus Emblica ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Phenolic Extract

Abstract Background Ethnobotany knowledge in a community has shaped local wisdom in utilizing plants to treat diseases, such as the use of Malaka (Phyllanthus emblica) flesh to treat type 2 diabetes. This study presented evidence that the phenolic extract of the Malaka flesh could reduce blood sugar levels in the diabetic induced rats. Methods The phenolic extract of the P. emblica was administrated to the glucose-induced rats of the Wistar strain Rattus norvegicus for 14 days of treatment where the Metformin was used as a positive control. The data generated were analyzed by the two-way ANOVA Software related to the blood glucose level and by SAS Software related to the histopathological studies at a significant 95% confidence. Results The phenolic extract with concentrations of 100 and 200 mg/kg body weight could reduce blood glucose levels in diabetic rats. The post hoc Dunnet test showed that the administration of the extract to the rats with a concentration of 100 mg/kg body weight demonstrated a very significant decrease in blood glucose levels and repaired damaged cells better than administering the extract at a concentration of 200 mg/kg weight body. Conclusion The evidence indicated that the phenolic extract of the Malaka flesh can be utilized as anti type 2 Diabetes mellitus without damaging other organs.

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