The Interlinking Metabolic Association between Type 2 Diabetes Mellitus and Cancer: Molecular Mechanisms and Therapeutic Insights.

Type 2 diabetes mellitus (T2DM) and cancer share common risk factors including obesity, inflammation, hyperglycemia, and hyperinsulinemia. High insulin levels activate the PI3K/Akt/mTOR signaling pathway promoting cancer cell growth, survival, proliferation, metastasis, and anti-apoptosis. The inhibition of the PI3K/Akt/mTOR signaling pathway for cancer remains a promising therapy; however, drug resistance poses a major problem in clinical settings resulting in limited efficacy of agents; thus, combination treatments with therapeutic inhibitors may solve the resistance to such agents.

Thapsigargin and Tunicamycin Block SARS-CoV-2 Entry into Host Cells via Differential Modulation of Unfolded Protein Response (UPR), AKT Signaling, and Apoptosis.

Background: SARS-Co-V2 infection can induce ER stress-associated activation of unfolded protein response (UPR) in host cells, which may contribute to the pathogenesis of COVID-19. To understand the complex interplay between SARS-Co-V2 infection and UPR signaling, we examined the effects of acute pre-existing ER stress on SARS-Co-V2 infectivity.

Methods: Huh-7 cells were treated with Tunicamycin (TUN) and Thapsigargin (THA) prior to SARS-CoV-2pp transduction (48 h p.

Differential Regulation of Glucosylceramide Synthesis and Efflux by Golgi and Plasma Membrane Bound ABCC10.

Glucosylceramide (GlcCer) synthesis by the enzyme glucosylceramide synthase (GCS) occurs on the cytosolic leaflet of the Golgi and is the first important step for the synthesis of complex glycosphingolipids (GSLs) that takes place inside the lumen. Apart from serving as a precursor for glycosylation, newly synthesized GlcCer is also transported to the plasma membrane and secreted onto HDL in the circulation. The mechanism by which GlcCer is transported to HDL remains unclear.

Association of Advanced Lipoprotein Subpopulation Profiles with Insulin Resistance and Inflammation in Patients with Type 2 Diabetes Mellitus.

Plasma lipoproteins exist as several subpopulations with distinct particle number and size that are not fully reflected in the conventional lipid panel. In this study, we sought to quantify lipoprotein subpopulations in patients with type 2 diabetes mellitus (T2DM) to determine whether specific lipoprotein subpopulations are associated with insulin resistance and inflammation markers. The study included 57 patients with T2DM (age, 61.

ATP-Binding Cassette Protein ABCC10 Deficiency Prevents Diet-Induced Obesity but Not Atherosclerosis in Mice.

Excess plasma lipid levels are a risk factor for various cardiometabolic disorders. Studies have shown that improving dyslipidemia lowers the progression of these disorders. In this study, we investigated the role of ATP-binding cassette transporter C10 (ABCC10) in regulating lipid metabolism.

Reduction in Insulin Mediated ERK Phosphorylation by Palmitate in Liver Cells Is Independent of Fatty Acid Induced ER Stress.

Saturated free fatty acids (FFAs) such as palmitate in the circulation are known to cause endoplasmic reticulum (ER) stress and insulin resistance in peripheral tissues. In addition to protein kinase B (AKT) signaling, extracellular signal-regulated kinase (ERK) has been implicated in the development of insulin resistance. However, there are conflicting data regarding role of ERK signaling in ER stress-induced insulin resistance.

Lipid Raft Integrity and Cellular Cholesterol Homeostasis Are Critical for SARS-CoV-2 Entry into Cells.

Lipid rafts in cell plasma membranes play a critical role in the life cycle of many viruses. However, the involvement of membrane cholesterol-rich lipid rafts in the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into target cells is not well known. In this study, we investigated whether the presence of cholesterol-rich microdomains is required for the entry of SARS-CoV-2 into host cells.

Relationship between the Soluble F11 Receptor and Annexin A5 in African Americans Patients with Type-2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is characterized by endothelial dysfunction, increased thrombogenicity, and inflammation. The soluble human F11 receptor (sF11R) and annexin A5 (ANXA5) play crucial roles in inflammatory thrombosis and atherosclerosis. We examined the relationship between circulating sF11R and ANXA5 and their impact on endothelial function.

Molecular Mechanisms of Sphingolipid Transport on Plasma Lipoproteins.

Sphingolipids are biomolecules with diverse physiological functions in signaling as well as plasma membrane structure. They are associated with either cellular membranes or plasma lipoproteins and any changes in their levels may contribute to certain metabolic diseases. Sphingolipids are evenly distributed in lipoproteins and may be used as prognostic and diagnostic markers.

Diet-induced differential effects on plasma lipids secretion by the inositol-requiring transmembrane kinase/endoribonuclease 1α.

Intestinal and hepatic lipid metabolism plays an essential role in regulating plasma lipid levels. These lipids are mobilized on apolipoprotein B (apoB)-containing lipoproteins and their plasma homeostasis is maintained by balancing production and catabolism. Microsomal triglyceride transfer protein (MTP) which is expressed mainly in the intestine and liver plays an essential role in regulating the assembly and secretion of apoB-lipoproteins.

Association between nitrated lipoproteins and vascular function in type 2 diabetes.

Higher levels of nitrated lipoproteins (NT-HDL and NT-LDL) were found in blood and atherosclerotic plaques of patients with coronary artery disease. We aimed to examine the relationship between plasma NT-HDL and NT-LDL and diabetic vascular dysfunction. The study included 125 African-American patients with T2DM.

Regulation of Sphingolipid Metabolism by MicroRNAs: A Potential Approach to Alleviate Atherosclerosis.

The rapidly expanding field of bioactive lipids is exemplified by the many sphingolipids, which are structurally and functionally diverse molecules with significant physiologic functions. These sphingolipids are main constituents of cellular membranes and have been found associated with plasma lipoproteins, and their concentrations are altered in several metabolic disorders such as atherosclerosis, obesity, and diabetes. Understanding the mechanisms that regulate their biosynthesis and secretion may provide novel information that might be amenable to therapeutic targeting in the treatment of these diseases.

Epigenetic regulation of genes involved in the reverse cholesterol transport through interaction with miRNAs.

microRNAs (miRNAs) are a group of small non-coding RNA molecules known to regulate target genes at the post-transcriptional level. miRNAs are implicated in the regulation of multiple pathophysiological processes including dyslipidemia, a major risk factor for atherosclerosis. Emerging evidence suggests that miRNAs act as a novel class of epigenetic regulators of high-density lipoproteins cholesterol (HDL-C) from synthesis to clearance contributing remarkably to the pathogenesis of atherosclerosis.

Epigenetic Regulation of ATP-Binding Cassette Protein A1 () Gene Expression: A New Era to Alleviate Atherosclerotic Cardiovascular Disease.

The most important function of high density lipoprotein (HDL) is its ability to remove cholesterol from cells and tissues involved in the early stages of atherosclerosis back to the liver for excretion. The ATP-binding cassette transporters ABCA1 and ABCG1 are responsible for the major part of cholesterol efflux to HDL in macrophage foam cells. Thus, promoting the process of reverse cholesterol transport (RCT) by upregulating mainly ABCA1 remains one of the potential targets for the development of new therapeutic agents against atherosclerosis.

The "forgotten" modified lipoprotein subspecies.

Insights from preclinical and clinical studies have attempted to highlight the importance of modified lipoprotein particles in the pathogenesis of cardiovascular diseases (CVD). However, evidence is not conclusive. Since there is a relative dearth of clinical research in collecting useful information from traditional advanced lipoproteins testing, this present editorial introduces the aim of a special issue on modified lipoproteins as potential biomarkers for CVD.

Precipitating factors and targeted therapies in combating the perils of sickle cell disease--- A special nutritional consideration.

Nutritional research in sickle cell disease has been the focus in recent times owing to not only specific nutritional deficiencies, but also the improvements associated with less painful episodes. Though hydroxyurea remains the drug of choice, certain adverse health effects on long term supplementation makes room for researches of different compounds. Macro and micro nutrient deficiencies, along with vitamins, play an important role in not only meeting the calorific needs, but also reducing clinical complications and growth abnormalities.

Human serum preβ1-high density lipoprotein levels are independently and negatively associated with coronary artery diseases.

Background: Serum preβ1-high density lipoprotein (preβ1-HDL) was defined by two-dimensional non-denaturing linear gel electrophoresis and apolipoprotein A-I immuno-blotting. Serum preβ1-HDL seems to play an important role in reverse cholesterol transport, a well-known anti-atherosclerosis process. However, there are still debatable questions for its quantification and coronary artery disease (CAD) relevance.

Mice subjected to aP2-Cre mediated ablation of microsomal triglyceride transfer protein are resistant to high fat diet induced obesity.

Background: Microsomal triglyceride transfer protein (MTP) is essential for the assembly of lipoproteins. MTP has been shown on the surface of lipid droplets of adipocytes; however its function in adipose tissue is not well defined. We hypothesized that MTP may play critical role in adipose lipid droplet formation and expansion.

Nitrated apolipoprotein AI/apolipoprotein AI ratio is increased in diabetic patients with coronary artery disease.

Aims/hypothesis: Recent studies have suggested that determination of HDL function may be more informative than its concentration in predicting its protective role in coronary artery disease (CAD). Apolipoprotein AI (apoAI), the major protein of HDL, is nitrosylated in vivo to nitrated apoAI (NT-apoAI) that might cause dysfunction. We hypothesized that NT-apoAI/apoAI ratio might be associated with diabetes mellitus (DM) in CAD patients.

Plasma Nitration of High-Density and Low-Density Lipoproteins in Chronic Kidney Disease Patients Receiving Kidney Transplants.

Background: Functional abnormalities of high-density lipoprotein (HDL) could contribute to cardiovascular disease in chronic kidney disease patients. We measured a validated marker of HDL dysfunction, nitrated apolipoprotein A-I, in kidney transplant recipients to test the hypothesis that a functioning kidney transplant reduces serum nitrated apoA-I concentrations.

Methods: Concentrations of nitrated apoA-I and apoB were measured using indirect sandwich ELISA assays on sera collected from each transplant subject before transplantation and at 1, 3, and 12 months after transplantation.

Nutrition & Metabolism Classics: a disconnect between highly cited and highly accessed articles.

Nutrition & Metabolism has grown considerably in the ten years since its first article was published. To see how papers published in the journal had an impact we have identified some of the most popular articles in order to measure their influence, observe which fields are important to our readers, and try to explain what made these articles Nutrition & Metabolism "Classics".

Nitrated apolipoprotein A-I, a potential new cardiovascular marker, is markedly increased in low high-density lipoprotein cholesterol subjects.

Background: Oxidative stress plays an important role in the pathogenesis of coronary artery disease. Recent work showed that high-density lipoproteins isolated from atherosclerotic lesions and blood of patients with established coronary artery disease contain elevated levels of nitrated apolipoprotein A-I. Methods to quantify nitrated apolipoprotein A-I in the plasma may facilitate in the determination of a correlation between plasma levels of nitrated apolipoprotein A-I and risk of atherosclerosis.