scholarly journals Circulating protein signatures and causal candidates for type 2 diabetes

2020 ◽  
Author(s):  
Ada Admin ◽  
Valborg Gudmundsdottir ◽  
Shaza B Zaghlool ◽  
Valur Emilsson ◽  
Thor Aspelund ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Serum Proteins ◽  
Serum Levels ◽  
The Body ◽  
Incident Type ◽  
Complex Processes ◽  
Proteomics Approach ◽  
Independent Case

The increasing prevalence of type 2 diabetes poses a major challenge to societies worldwide. Blood-based factors like serum proteins are in contact with every organ in the body to mediate global homeostasis and may thus directly regulate complex processes such as aging and the development of common chronic diseases. We applied a data-driven proteomics approach, measuring serum levels of 4,137 proteins in 5,438 elderly Icelanders and identified 536 proteins associated with prevalent and/or incident type 2 diabetes. We validated a subset of the observed associations in an independent case-control study of type 2 diabetes. These protein associations provide novel biological insights into the molecular mechanisms that are dysregulated prior to and following the onset of type 2 diabetes and can be detected in serum. A bi-directional two-sample Mendelian randomization analysis indicated that serum changes of at least 23 proteins are downstream of the disease or its genetic liability, while 15 proteins were supported as having a causal role in type 2 diabetes.

scholarly journals Circulating protein signatures and causal candidates for type 2 diabetes

2020 ◽  
Author(s):  
Ada Admin ◽  
Valborg Gudmundsdottir ◽  
Shaza B Zaghlool ◽  
Valur Emilsson ◽  
Thor Aspelund ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Serum Proteins ◽  
Serum Levels ◽  
The Body ◽  
Incident Type ◽  
Complex Processes ◽  
Proteomics Approach ◽  
Independent Case

The increasing prevalence of type 2 diabetes poses a major challenge to societies worldwide. Blood-based factors like serum proteins are in contact with every organ in the body to mediate global homeostasis and may thus directly regulate complex processes such as aging and the development of common chronic diseases. We applied a data-driven proteomics approach, measuring serum levels of 4,137 proteins in 5,438 elderly Icelanders and identified 536 proteins associated with prevalent and/or incident type 2 diabetes. We validated a subset of the observed associations in an independent case-control study of type 2 diabetes. These protein associations provide novel biological insights into the molecular mechanisms that are dysregulated prior to and following the onset of type 2 diabetes and can be detected in serum. A bi-directional two-sample Mendelian randomization analysis indicated that serum changes of at least 23 proteins are downstream of the disease or its genetic liability, while 15 proteins were supported as having a causal role in type 2 diabetes.

scholarly journals Deep serum proteomics reveal biomarkers and causal candidates for type 2 diabetes

2019 ◽  
Author(s):  
Valborg Gudmundsdottir ◽  
Valur Emilsson ◽  
Thor Aspelund ◽  
Marjan Ilkov ◽  
Elias F Gudmundsson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Serum Proteins ◽  
Protein Profile ◽  
Disease Onset ◽  
Serum Levels ◽  
The Body ◽  
Protein Biomarkers ◽  
Clinical Value ◽  
Serum Proteomics

AbstractThe prevalence of type 2 diabetes mellitus (T2DM) is expected to increase rapidly in the next decades, posing a major challenge to societies worldwide. The emerging era of precision medicine calls for the discovery of biomarkers of clinical value for prediction of disease onset, where causal biomarkers can furthermore provide actionable targets. Blood-based factors like serum proteins are in contact with every organ in the body to mediate global homeostasis and may thus directly regulate complex processes such as aging and the development of common chronic diseases. We applied a data-driven proteomics approach measuring serum levels of 4,137 proteins in 5,438 Icelanders to discover novel biomarkers for incident T2DM and describe the serum protein profile of prevalent T2DM. We identified 536 proteins associated with incident or prevalent T2DM. Through LASSO penalized logistic regression analysis combined with bootstrap resampling, a panel of 20 protein biomarkers that accurately predicted incident T2DM was identified with a significant incremental improvement over traditional risk factors. Finally, a Mendelian randomization analysis provided support for a causal role of 48 proteins in the development of T2DM, which could be of particular interest as novel therapeutic targets.

scholarly journals Serum Levels of Apolipoproteins and Incident Type 2 Diabetes: A Prospective Cohort Study

Diabetes Care ◽  
2016 ◽  
Vol 40 (3) ◽  
pp. 346-351 ◽  
Author(s):  
Adela Brahimaj ◽  
Symen Ligthart ◽  
M. Arfan Ikram ◽  
Albert Hofman ◽  
Oscar H. Franco ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cohort Study ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Serum Levels ◽  
Incident Type ◽  
Incident Type 2 Diabetes

scholarly journals Effect of Agmatine on Non-Alcoholic Fatty Liver Disease Induced by Type 2 Diabetes in Rats

2021 ◽  
pp. 127-134
Author(s):  
Samar F. Miski ◽  
Mai A. Alim A. Sattar Ahmad ◽  
Ahmed Esmat
Keyword(s):  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Histopathological Examination ◽  
Fasting Blood Glucose ◽  
Serum Levels ◽  
Current Data ◽  
Hepatoprotective Effect ◽  
Control Group ◽  
Alcoholic Fatty Liver

Aim: To determine the potential hepatoprotective effect of Agmatine (AGM) on NAFLD-induced by Type 2 diabetes mellitus (T2DM) in rats. Study design:  Forty male Wistar rats weighing from (200 -250 g) were distributed at random into five groups (8 rats per group): group 1 as control; group 2 as untreated-T2DM; groups 3 & 4 as T2DM cotreated with AGM (40 & 80 mg/kg/d), while group 5 T2DM cotreated with Silymarin (100 mg/kg/d). Place and duration of study: Department of Pharmacology, Faculty of Medicine, king Abdul-Aziz University; between October 2020 and January 2021. Methodology: A rat model of T2DM with NAFLD complication was established by feeding rats with 10% fructose in drinking water and intraperitoneally injecting them with a single low dose of streptozotocin (STZ) (45mg/kg). The fasting blood glucose was detected, serum levels of hepatic biomarkers were all assessed. Moreover, histopathological examination was performed by hematoxylin and eosin (H&E) staining. Results: STZ induced T2DM in rats causes a significant (p<0.05, n=8) rise in serum levels of FBG, ALT, AST, TB, TC, TG, and LDL in comparison with the corresponding control group. Co-treatment with AGM (40 & 80 mg/kg) and silymarin significantly alleviated hyperglycemia and amended hepatic biomarkers that was reflected on improved histopathological changes. Conclusion: The current data suggest that oral AGM co-treatment could have a hepatoprotective effect against T2DM associated with NAFLD in rats. Further investigations are recommended to elucidate molecular mechanisms accountable for the useful effects of AGM on hepatocytes.

Vitamin K Insufficiency in an India Population: A Pilot Study (Preprint)

2021 ◽  
Author(s):  
Sidney Stohs ◽  
Ashok DB Vaidya ◽  
Jayesh Sheth ◽  
Shashank Jadhav ◽  
Umakant Mahale ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Vitamin K ◽  
Serum Levels ◽  
Vitamin K2 ◽  
The Body ◽  
Coagulation Cascade ◽  
Dietary Intakes ◽  
Fluorescence Detector ◽  
Geographical Regions

BACKGROUND The fat-soluble K vitamins K1 and K2 are well recognized and exert an essential biological role in the blood coagulation cascade. However, vitamin K is less known for its non-essential roles in participating in the growing family of vitamin K-dependent proteins that promote various functions of organs and systems in the body, sustaining health and preventing disease. These less well-known actions depend on the availability of vitamin K for non-essential multi-tasking functions. This fat-soluble vitamin is available predominantly through selective dietary intakes, and its presence is absent or very low in many diets. The lack of vitamin K for non-essential biological functions exemplifies vitamin/nutritional element insufficiency, which is different from a clinically apparent vitamin deficiency. OBJECTIVE The current epidemiological study evaluated the nutritional status of vitamin K in a sample of the Indian population and its content in staple Indian foods. METHODS Serum levels of vitamin K1 and vitamin K2 in the form of MK-7 were assessed by high-performance liquid chromatography (HPLC) coupled with a fluorescence detector in 209 patients with Type 2 diabetes and 50 healthy volunteers and in common, staple foods in India. RESULTS The results indicate that in comparison to populations with high and low serum levels in various geographical regions, the sample of India population of apparently healthy individuals and Type 2 diabetes patients showed low (insufficient) levels of vitamin K2 (menaquinone-7). The staple, commonly consumed Indian foods that were tested in the study showed undetectable content of vitamin K2. CONCLUSIONS The general population could benefit from the consumption of vitamin K2 in the form of MK-7 supplements, with emphasis on patients with diabetes, elevated blood pressure, a harbinger of cardiovascular disease, and compromised immune systems. The results can be extrapolated world-wide. CLINICALTRIAL CTRI 2019/05/014246

scholarly journals SHBG-C57BL/ksJ-db/db: A New Mouse Model to Study SHBG Expression and Regulation During Obesity Development

Endocrinology ◽  
2015 ◽  
Vol 156 (12) ◽  
pp. 4571-4581 ◽  
Author(s):  
Cristina Saéz-López ◽  
Marta Rivera-Giménez ◽  
Cristina Hernández ◽  
Rafael Simó ◽  
David M. Selva
Keyword(s):  
Type 2 Diabetes ◽  
Mouse Model ◽  
Molecular Mechanisms ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
The Body ◽  
Sex Hormone Binding Globulin ◽  
In Vivo Models ◽  
The Metabolic Syndrome

Low plasma sex hormone-binding globulin (SHBG) levels in overweight individuals are a biomarker for the metabolic syndrome and are predictive of type 2 diabetes and cardiovascular disease risk. There are no in vivo models to study SHBG expression and regulation during obesity development. The main reason for this is that the obesity-prone rodent models cannot be used to study this issue, because rodents, unlike humans, do not express the SHBG gene in their livers. We have developed a unique mouse model that expresses the human SHBG, and it develops obesity, by crossing the human SHBG transgenic mice with the C57BL/ksJ-db/db mice. The results obtained with the SHBG-C57BL/ksJ-db/db mouse model have allowed us to determine that the SHBG overexpression in the C57BL/ksJ-db/db reduced the body weight gain but did not change the metabolic profile of these mice. Moreover, we elucidated the molecular mechanisms and transcription factors causing the SHBG down-regulation during obesity development, which involved changes in liver hepatocyte nuclear factor 4α and peroxisome proliferator-activated receptor-γ mRNA and protein levels. Furthermore, these results were confirmed using human liver biopsies. Importantly, we also showed that this model resembles what occurs in human obese subjects, because plasma SHBG and total testosterone levels where reduced in obese mice when compared with lean mice. Future research using this unique mouse model will determine the role of SHBG in the development and progression of obesity, type 2 diabetes, or fatty liver disease.

scholarly journals Serum levels of interleukin-22, cardiometabolic risk factors and incident type 2 diabetes: KORA F4/FF4 study

2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Christian Herder ◽  
Julia M. Kannenberg ◽  
Maren Carstensen-Kirberg ◽  
Cornelia Huth ◽  
Christa Meisinger ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Cardiometabolic Risk ◽  
Serum Levels ◽  
Cardiometabolic Risk Factors ◽  
Incident Type ◽  
Interleukin 22 ◽  
Incident Type 2 Diabetes

scholarly journals RANTES/CCL5 gene polymorphisms, serum concentrations, and incident type 2 diabetes: results from the MONICA/KORA Augsburg case–cohort study, 1984–2002

2008 ◽  
Vol 158 (5) ◽  
pp. R1-R5 ◽  
Author(s):  
Christian Herder ◽  
Thomas Illig ◽  
Jens Baumert ◽  
Martina Müller ◽  
Norman Klopp ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cohort Study ◽  
Gene Polymorphisms ◽  
Serum Levels ◽  
Population Based ◽  
Nucleotide Polymorphisms ◽  
Serum Concentrations ◽  
Incident Type ◽  
Incident Type 2 Diabetes

ObjectiveRegulated on activation, normal T-cell expressed and secreted (RANTES)/chemokine(C-C motif) ligand (CCL5) is expressed by adipocytes, and serum levels of RANTES are increased in obesity and type 2 diabetes. The aim of this study was to test the hypothesis that RANTES is involved in the pathogenesis of type 2 diabetes by analyzing the triangular association between CCL5 gene polymorphisms, systemic RANTES concentrations, and incident type 2 diabetes in a large prospective study.Subjects and methodsThe study is based on 502 individuals (293 men and 209 women) and 1632 individuals (859 men and 773 women) with and without incident type 2 diabetes from the population-based MONItoring of Trends and Determinants in Cardiovascular Disease (MONICA)/Cooperative Health Research in the Region of Augsburg (KORA) case–cohort study respectively (mean follow-up time±s.d. 10.1±4.9 years). CCL5 genotypes and RANTES serum concentrations were determined and associations between genotypes, haplotypes, serum levels, and incident type 2 diabetes were assessed.ResultsMinor alleles of four single nucleotide polymorphisms were associated with lower RANTES levels (Padditive between 1.2×10−9 and 3.1×10−8), but neither genotypes, haplotypes, nor serum levels were associated with incident type 2 diabetes.ConclusionsOur data suggest that RANTES/CCL5 gene variants and serum levels are not causally related with type 2 diabetes and that elevated RANTES levels in patients with type 2 diabetes may be a consequence of hyperglycemia. However, our findings cannot preclude a local role in adipose tissue where RANTES expression may contribute to leukocyte infiltration and a proinflammatory state.

IS THERE A CONNECTION BETWEEN PYLORIC HELICOBACTER INFECTION AND METABOLIC DISORDERS?

2019 ◽  
Vol 25 (4) ◽  
pp. 210-214
Author(s):  
Serafima V. German ◽  
A. V Modestova ◽  
I. E Zykova ◽  
I. G Nikitin
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Disorders ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Overweight And Obesity ◽  
The Body ◽  
Lipoprotein Cholesterol ◽  
High Prevalence

Relevance. There are numerous publications of foreign authors about relationship between Pyloric Helicobacter (H. p.) infection with several gastroduodenal diseases, including metabolic disorders. Russia is one of the countries with high prevalence of H. p. infection and metabolic disorders. Determining their relationship is important for both prevention and treatment of metabolic disorders. Purpose - study the possibility of relationship between H. p. infection and type 2 diabetes, dyslipidemia, overweight and obesity. Methods and materials. The study included 1487 working residents of Moscow and the Moscow region, 931 men and 556 women, aged 21 to 77 years (median - 46). H. p. infection was diagnosed by detecting antibodies to IgG bacteria in the blood serum. In 698 infected individuals, the presence of a CagA strain, a marker of virulence of the bacterium, was studied using ELISA. Serum levels of basal glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides were studied, and the body mass index was determined. Results. Infection was discovered in 1348 people (90.6%), CagA positive - 392 (56.2%). Type 2 diabetes was diagnosed in 77 people, 74 - H. p. positive (5.5% ), and 3 - H. p. negative (2.1%). CagA was studied for 31 persons with diabetes. CagA-positive bacterial strain was determined in 22 cases out of 31 (70.1%, p 0,05, by criterion χ²). Among H. p. positive, overweight was registered in 884 cases (65.6%), in H. p. negative - in 74 cases (53.2%) (p

Research work undertaken in the Inokuchi Laboratory – Chronic inflammation & chronic disease research including diabetes and metabolic diseases.

Impact ◽  
2020 ◽  
Vol 2020 (7) ◽  
pp. 22-24
Author(s):  
Jin-ichi Inokuchi
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Inflammation ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Research Work ◽  
The Body ◽  
Amplification Loop ◽  
Inside Out ◽  
Ganglioside Species

Today, type 2 diabetes is typically treated by lowering sugar in the blood and increasing the sensitivity of muscle cells to insulin. However, novel discoveries could allow future treatments to target the molecular mechanisms in our bodies that generate insulin resistance – effectively preventing the biological chain of events that causes chronic inflammation and disease to initially occur. Professor Jin-ichi Inokuchi heads the Glycopathology Laboratory at Tohoku Medical and Pharmaceutical University, Japan. Situated within the Institute of Molecular Biomembrane and Glycobiology, the Laboratory focuses on gangliosides and their roles in inflammatory cycles. The scientists are particularly interested in GM3 ganglioside species, as their previous research has indicated that the increased presence of anti-inflammatory GM3 species and decreased presence of pro-inflammatory GM3 species have the power to alter inflammatory cycles in the body, thus contributing to chronic inflammation and associated diseases. Recently, Inokuchi and his colleagues' research revealed some interesting insights regarding GM3. Namely, they discovered that GM3 plays an important role in an inflammation amplification loop that affects diseases involving chronic inflammation, such as type 2 diabetes and metabolic diseases closely linked with obesity. 'Collectively, we propose a novel inflammation loop triggered by GM3 molecular species,' asserts Inokuchi. Inokuchi's research provides an avenue for tackling these conditions from the inside out. By focusing on the biological processes involved in these lifestyle-related chronic diseases, it may be possible to treat type 2 diabetes and metabolic diseases more efficiently.

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