scholarly journals Apolipoprotein M—A Marker or an Active Player in Type II Diabetes?

2021 ◽  
Vol 12 ◽  
Author(s):  
Christina Christoffersen
Keyword(s):  
Cholesterol Metabolism ◽  
High Density Lipoproteins ◽  
Apolipoprotein M ◽  
Active Player ◽  
Sphingosine 1 Phosphate ◽  
Diabetes Development ◽  
Diabetes And Obesity ◽  
Harmful Effects

Apolipoprotein M (apoM) is a member of the lipocalin superfamily and an important carrier of the small bioactive lipid sphingosine-1-phosphate (S1P). The apoM/S1P complex is attached to all lipoproteins, but exhibits a significant preference for high-density lipoproteins. Although apoM, S1P, and the apoM/S1P complex have been discovered more than a decade earlier, the overall function of the apoM/S1P complex remains controversial. Evidence suggests that the complex plays a role in inflammation and cholesterol metabolism and is important for maintaining a healthy endothelial barrier, regulating the turnover of triglycerides from lipoproteins, and reducing cholesterol accumulation in vessel walls. Recent studies have also addressed the role of apoM and S1P in the development of diabetes and obesity. However, limited evidence is available, and the data published so far deviates. This review discusses the specific elements indicative of the protective or harmful effects of apoM, S1P, and the apoM/S1P complex on type 2 diabetes development. Since drugs targeting the S1P system and its receptors are available and could be potentially used for treating diabetes, this research topic is a pertinent one.

scholarly journals Transkingdom interactions between Lactobacilli and hepatic mitochondria attenuate western diet-induced diabetes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Richard R. Rodrigues ◽  
Manoj Gurung ◽  
Zhipeng Li ◽  
Manuel García-Jaramillo ◽  
Renee Greer ◽  
...  
Keyword(s):  
Functional Role ◽  
Reduced Glutathione ◽  
Western Diet ◽  
Data Driven ◽  
Data Driven Approach ◽  
Probiotic Strains ◽  
Host Metabolism ◽  
Harmful Effects

AbstractWestern diet (WD) is one of the major culprits of metabolic disease including type 2 diabetes (T2D) with gut microbiota playing an important role in modulating effects of the diet. Herein, we use a data-driven approach (Transkingdom Network analysis) to model host-microbiome interactions under WD to infer which members of microbiota contribute to the altered host metabolism. Interrogation of this network pointed to taxa with potential beneficial or harmful effects on host’s metabolism. We then validate the functional role of the predicted bacteria in regulating metabolism and show that they act via different host pathways. Our gene expression and electron microscopy studies show that two species from Lactobacillus genus act upon mitochondria in the liver leading to the improvement of lipid metabolism. Metabolomics analyses revealed that reduced glutathione may mediate these effects. Our study identifies potential probiotic strains for T2D and provides important insights into mechanisms of their action.

scholarly journals Gut as an emerging organ for the treatment of diabetes: focus on mechanism of action of bariatric and endoscopic interventions

2018 ◽  
Vol 237 (1) ◽  
pp. R1-R17 ◽  
Author(s):  
Martin Haluzík ◽  
Helena Kratochvílová ◽  
Denisa Haluzíková ◽  
Miloš Mráz
Keyword(s):  
Type 2 Diabetes ◽  
Bariatric Surgery ◽  
Therapeutic Option ◽  
Gastrointestinal Hormones ◽  
Less Invasive ◽  
Treatment Of Diabetes ◽  
Endoscopic Methods ◽  
Diabetes And Obesity

Increasing worldwide prevalence of type 2 diabetes mellitus and its accompanying pathologies such as obesity, arterial hypertension and dyslipidemia represents one of the most important challenges of current medicine. Despite intensive efforts, high percentage of patients with type 2 diabetes does not achieve treatment goals and struggle with increasing body weight and poor glucose control. While novel classes of antidiabetic medications such as incretin-based therapies and gliflozins have some favorable characteristics compared to older antidiabetics, the only therapeutic option shown to substantially modify the progression of diabetes or to achieve its remission is bariatric surgery. Its efficacy in the treatment of diabetes is well established, but the exact underlying modes of action are still only partially described. They include restriction of food amount, enhanced passage of chymus into distal part of small intestine with subsequent modification of gastrointestinal hormones and bile acids secretion, neural mechanisms, changes in gut microbiota and many other possible mechanisms underscoring the importance of the gut in the regulation of glucose metabolism. In addition to bariatric surgery, less-invasive endoscopic methods based on the principles of bariatric surgery were introduced and showed promising results. This review highlights the role of the intestine in the regulation of glucose homeostasis focusing on the mechanisms of action of bariatric and especially endoscopic methods of the treatment of diabetes. A better understanding of these mechanisms may lead to less invasive endoscopic treatments of diabetes and obesity that may complement and widen current therapeutic options.

Abstract 557: Type 2 Diabetes is Associated With Impaired High-Density Lipoprotein Endothelial Protective Function

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Tomas Vaisar ◽  
Erica Couzens ◽  
Arnold Hwang ◽  
Andrew N Hoofnagle ◽  
Carolyn E Barlow ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Endothelial Cells ◽  
Endothelial Function ◽  
Lipid Profile ◽  
High Density ◽  
High Density Lipoproteins ◽  
Protective Function ◽  
Enos Activity ◽  
Sphingosine 1 Phosphate

Aim: One of the hallmarks of diabetes is impaired endothelial function. High density lipoproteins (HDL) can exert protective effects on endothelium stimulating NO production and protecting from inflammation. Previous study suggested that HDL in obese people with diabetes and metabolic syndrome and markedly low HDL-C lost endothelial protective function. We aimed to test whether type 2 diabetes impairs HDL endothelium protective functions in people with otherwise normal lipid profile. Methods: In a case-control study (n=40 per group) nested in the Cooper Center Longitudinal Study, we isolated HDL and measured its ability to stimulate activity of endothelial nitric oxide synthase (eNOS; phosphorylation of Ser1177) in endothelial cells and the ability of HDL to suppress inflammatory response of endothelial cells (NFkB activation). Additionally, we also measured by LCMS levels of sphingosine-1-phosphate (S1P) and plasma P-selectin by ELISA. Results: The HDL in people with type 2 diabetes lost almost 40% of its ability to stimulate eNOS activity (P<0.001) and 20% of its ability to suppress inflammation in endothelial cells ( P <0.001) compared to non-diabetic controls despite similar BMI and lipid profile (HDL-C, LDL-C, TC, TG).The ability of HDL to stimulate eNOS activity was negatively associated with plasma levels of P-selectin, an established marker of endothelial dysfunction (r=–0.32, P <0.001). Furthermore, sphingosine-1-phosphate (S1P) levels were decreased in plasma of people with diabetes ( P =0.017) and correlated strongly with HDL-mediated eNOS activation. Conclusions: Collectively, our data suggest that HDL in individuals with type 2 diabetes loses its ability to maintain proper endothelial function independent of HDL-C, perhaps due to loss of S1P, and may contribute to development of diabetic complications.

scholarly journals Increased Expression of Meteorin-Like Hormone in Type 2 Diabetes and Obesity and Its Association with Irisin

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1283 ◽  
Author(s):  
AlKhairi ◽  
Cherian ◽  
Abu-Farha ◽  
Madhoun ◽  
Nizam ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Plasma Levels ◽  
Positive Association ◽  
Diabetic Patients ◽  
Metabolic Dysregulation ◽  
Strong Positive Association ◽  
Metabolic Biomarkers ◽  
Diabetes And Obesity

Type 2 diabetes (T2D) is a growing pandemic associated with metabolic dysregulation and chronic inflammation. Meteorin-like hormone (METRNL) is an adipomyokine that is linked to T2D. Our objective was to evaluate the changes in METRNL levels in T2D and obesity and assess the association of METRNL levels with irisin. Overall, 228 Arab individuals were enrolled. Plasma levels of METRNL and irisin were assessed using immunoassay. Plasma levels of METRNL and irisin were significantly higher in T2D patients than in non-diabetic patients (p < 0.05). When the population was stratified based on obesity, METRNL and irisin levels were significantly higher in obese than in non-obese individuals (p < 0.05). We found a significant positive correlation between METRNL and irisin (r = 0.233 and p = 0.001). Additionally, METRNL and irisin showed significant correlation with various metabolic biomarkers associated with T2D and Obesity. Our data shows elevated METRNL plasma levels in individuals with T2D, further exacerbated with obesity. Additionally, a strong positive association was observed between METRNL and irisin. Further studies are necessary to examine the role of these proteins in T2D and obesity, against their ethnic background and to understand the mechanistic significance of their possible interplay.

scholarly journals The Protective Effect of Exercise in Neurodegenerative Diseases: The Potential Role of Extracellular Vesicles

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2182 ◽  
Author(s):  
Oliver K Fuller ◽  
Martin Whitham ◽  
Suresh Mathivanan ◽  
Mark A Febbraio
Keyword(s):  
Physical Activity ◽  
Extracellular Vesicles ◽  
Potential Role ◽  
The Body ◽  
Therapeutic Effects ◽  
Health And Wellbeing ◽  
Systemic Factors ◽  
Diabetes And Obesity

Physical activity has systemic effects on the body, affecting almost every organ. It is important not only for general health and wellbeing, but also in the prevention of diseases. The mechanisms behind the therapeutic effects of physical activity are not completely understood; however, studies indicate these benefits are not confined to simply managing energy balance and body weight. They also include systemic factors which are released into the circulation during exercise and which appear to underlie the myriad of benefits exercise can elicit. It was shown that along with a number of classical cytokines, active tissues also engage in inter-tissue communication via extracellular vesicles (EVs), specifically exosomes and other small EVs, which are able to deliver biomolecules to cells and alter their metabolism. Thus, EVs may play a role in the acute and systemic adaptations that take place during and after physical activity, and may be therapeutically useful in the treatment of a range of diseases, including metabolic disorders such as type 2 diabetes and obesity; and the focus of this review, neurological disorders such as Alzheimer’s disease.

Abstract 257: Apolipoprotein M Is Not Present in Prebeta-1 HDL Particles

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Lita A Freeman ◽  
Robert Shamburek ◽  
Angel Aponte ◽  
Gregory J Kato ◽  
Alan T Remaley
Keyword(s):  
Retinoic Acid ◽  
Small Particle ◽  
Plasma Levels ◽  
Reverse Cholesterol Transport ◽  
Cholesterol Efflux ◽  
Cholesterol Transport ◽  
Apolipoprotein M ◽  
Sphingosine 1 Phosphate ◽  
2D Gel

BACKGROUND: Apolipoprotein M (apoM) is a 25 kD plasma protein present mainly in HDL. It has a hydrophobic pocket for carrying ligands variously reported as retinol, all- trans -retinoic acid, 9- cis -retinoic acid, sphingosine-1-phosphate (S1P) and oxidized phospholipids. In addition to mediating the effects of S1P and modulating oxidative stress, apoM has been reported to enhance cholesterol efflux and to increase plasma levels of small, preβ1 HDL, a particle that efficiently accepts cholesterol effluxed from cholesterol-loaded cells and plays a key role in reverse cholesterol transport. ApoM is present in α-migrating HDL particles but whether it is also present in small preβ1 HDL particles is disputed. Establishing the absence or presence of apoM in preβ1 HDL particles is essential for understanding its role in reverse cholesterol transport. METHODS: We performed native-native 2D gel electrophoresis on healthy volunteer plasma to separate native HDL particles by size and charge. Particles were blotted onto a membrane and probed with antibodies to apoM or apoA-I to identify specific HDL particles associated with apoM. Similar experiments were performed with plasma from patients with apoE-deficiency or from patients with low plasma levels of apoA-I and HDL. We also performed native 1D electrophoresis to visualize lipoprotein particles containing apoM. Finally, native-native 2D gels of purified HDL were used for proteomics of preβ1 particles. RESULTS: apoM was present in two large α-migrating HDL particles and in LDL-sized particles, as well as in one small particle that did not contain apoA-I. apoA-I but not apoE was required for formation of the large apoM-containing HDL particles. The small apoM particle was unaffected in apoA-I- and apoE-deficient patients. apoM was not present in preβ1 particles. CONCLUSION: apoM is not a stable component of small preβ1 apoA-I-containing HDL particles but instead resides mainly in two large HDL molecules and in LDL-sized particles, as well as a small particle that does not contain apoA-I. The role of apoM in cholesterol efflux requires further evaluation.

scholarly journals Comorbidity status of deceased COVID-19 in-patients in Italy

2021 ◽  
Author(s):  
Davide Liborio Vetrano ◽  
Clare Tazzeo ◽  
Luigi Palmieri ◽  
Alessandra Marengoni ◽  
Alberto Zucchelli ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Older Persons ◽  
Logistic Regression Models ◽  
Neuropsychiatric Diseases ◽  
Clinical Profiles ◽  
Comorbidity Status ◽  
Diabetes And Obesity

Abstract Background Most COVID-19-related deaths have occurred in older persons with comorbidities. Specific patterns of comorbidities related to COVID-19 deaths have not been investigated. Methods A random sample of 6085 individuals in Italy who died in-hospital with confirmed COVID-19 between February and December 2020 were included. Observed to expected (O/E) ratios of disease pairs were computed and logistic regression models were used to determine the association between disease pairs with O/E values ≥ 1.5. Results Six pairs of diseases exhibited O/E values ≥ 1.5 and statistically significant higher odds of co-occurrence in the crude and adjusted analyses: (1) ischemic heart disease and atrial fibrillation, (2) atrial fibrillation and heart failure, (3) atrial fibrillation and stroke, (4) heart failure and COPD, (5) stroke and dementia, and (6) type 2 diabetes and obesity. Conclusion In those deceased in-hospital due to COVID-19 in Italy, disease combinations defined by multiple cardio-respiratory, metabolic, and neuropsychiatric diseases occur more frequently than expected. This finding indicates a need to investigate the possible role of these clinical profiles in the chain of events that lead to death in individuals who have contracted SARS-CoV-2.

scholarly journals Role of platelet-derived growth factor in type II diabetes mellitus and its complications

2020 ◽  
Vol 17 (4) ◽  
pp. 147916412094211
Author(s):  
Sihong Shen ◽  
Fuyan Wang ◽  
Alejandra Fernandez ◽  
Weining Hu
Keyword(s):  
Diabetes Mellitus ◽  
Growth Factors ◽  
Type Ii Diabetes ◽  
Critical Role ◽  
Type Ii Diabetes Mellitus ◽  
Regulate Cell Growth ◽  
Treatment Of Diabetes ◽  
Diabetes Development

Type 2 diabetes mellitus is a type of metabolic disorder characterized by hyperglycaemia with multiple serious complications, such as diabetic neuropathies, diabetic nephropathy, diabetic retinopathy, and diabetic foot. Platelet-derived growth factors are growth factors that regulate cell growth and division, playing a critical role in diabetes and its harmful complications. This review focused on the cellular mechanism of platelet-derived growth factors and their receptors on diabetes development. Furthermore, we raise some proper therapeutic molecular targets for the treatment of diabetes and its complications.

67 CHOLESTEROL METABOLISM AND OBESITY IN TYPE 2 DIABETES: ROLE OF PLASMA STEROLS

2008 ◽  
Vol 18 ◽  
pp. S51
Author(s):  
I. Marini ◽  
P. Bertucci ◽  
S. Zagari ◽  
M.R. Bollea ◽  
A. Lala
Keyword(s):  
Type 2 Diabetes ◽  
Cholesterol Metabolism

scholarly journals Hepatic FoxOs induce apolipoprotein M and are required for sphingosine-1-phosphate to bind high density lipoproteins

2019 ◽  
Author(s):  
María Concepción Izquierdo ◽  
Niroshan Shanmugarajah ◽  
Samuel X. Lee ◽  
Rebecca A. Haeusler
Keyword(s):  
Transcription Factors ◽  
Insulin Action ◽  
Leptin Receptor ◽  
High Density ◽  
High Density Lipoproteins ◽  
Total Plasma ◽  
Apolipoprotein M ◽  
Hdl Function ◽  
Sphingosine 1 Phosphate ◽  
Transcriptional Target

ABSTRACTThe FoxO family of transcription factors play an important role in mediating insulin action on glucose, lipid, and lipoprotein metabolism. Liver-specific triple FoxO knockout mice (L-FoxO1,3,4) have defects in expression of genes related to glucose production, bile acid synthesis, and high density lipoprotein (HDL)-cholesterol uptake. We have now identified Apolipoprotein M (Apom) as a novel transcriptional target of liver FoxO. ApoM is a liver-secreted apolipoprotein that is bound to HDL in the circulation, and it serves as a chaperone for the bioactive lipid, sphingosine-1-phosphate (S1P). Several recent studies have demonstrated that S1P bound to ApoM induces unique effects, compared to S1P bound to albumin. We now show that liver FoxOs are required for ApoM mRNA and protein expression, and that ApoM is a transcriptional target of FoxOs. Moreover, while total plasma S1P levels are similar between control and L-FoxO1,3,4 mice, S1P is nearly absent from HDL in L-FoxO1,3,4 mice, and is instead increased in the lipoprotein depleted fraction. We also observed that leptin receptor deficient db/db mice have low hepatic Apom mRNA, and low levels of ApoM and S1P in HDL, without changes in total plasma S1P. These data demonstrate that FoxO transcription factors are novel regulators of the ApoM-S1P pathway, and indicate a potential link between hepatic insulin action and HDL function.

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