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Topic Review
Type 2 Diabetes: Beta Cell Compensation and Death
Type 2 diabetes (T2D) has become a worldwide epidemic, primarily driven by obesity from overnutrition and sedentariness. Physiologically, T2D manifests as an inability of the pancreatic beta cells to produce and secrete a sufficient bolus of insulin to elicit a response in target cells to transport glucose from the blood and properly regulate glucose levels. Insulin is synthesized in the endoplasmic reticulum (ER) of pancreatic beta cells where it undergoes a series of post-translational modifications to form mature insulin. Insulin resistance requires more insulin to be produced by beta cells to compensate for these desensitized cells. Consequently, this compensation causes additional strain on beta cells. This stress primarily originates from the ER and can also trigger oxidative stress. These cellular stresses can lead to beta cell decompensation, manifested by dysfunction and eventually a loss of beta cell mass.
  • 1.0K
  • 04 Mar 2024
Topic Review
Immune Cell Type-Specific Metabolic Reprogramming
Immunometabolism is an emerging discipline in cancer immunotherapy. Tumor tissues are heterogeneous and influenced by metabolic reprogramming of the tumor immune microenvironment (TIME). In the TIME, multiple cell types interact, and the tumor and immune cells compete for limited nutrients, resulting in altered anticancer immunity. Therefore, metabolic reprogramming of individual cell types may influence the outcomes of immunotherapy. Understanding the metabolic competition for access to limited nutrients between tumor cells and immune cells could reveal the breadth and complexity of the TIME and aid in developing novel therapeutic approaches for cancer.
  • 1.0K
  • 18 Mar 2022
Topic Review
Non-Coding RNAs Biogenesis and Function
Non-coding RNAs (ncRNAs) have gained growing interest because of their potential role in IR modulation. NcRNAs are variable-length transcripts which are not translated into proteins but are involved in gene expression regulation. Thanks to their stability and easy detection in biological fluids, ncRNAs have been investigated as promising diagnostic and therapeutic markers in metabolic diseases, such as type 2 diabetes mellitus (T2D), obesity and non-alcoholic fatty liver disease (NAFLD). 
  • 1.0K
  • 13 Aug 2021
Topic Review
Plasminogen in Cancer
Fibrinolytic factors like plasminogen, tissue-type plasminogen activator (tPA), and urokinase plasminogen activator (uPA) dissolve clots. Though mere extracellular-matrix-degrading enzymes, fibrinolytic factors interfere with many processes during primary cancer growth and metastasis contributing to the hallmarks of cancer. Their many receptors give them access to cellular functions that tumor cells have widely exploited to promote tumor cell survival, growth, and metastatic abilities. Fibrinolytic factors give cancer cells tools to ensure their own survival by interfering with the signaling pathways involved in senescence, anoikis, and autophagy. Dependent on the cell type, plasminogen was shown to either enhance or suppress cancer cell survival via autophagy. The Kringle 5 of plasminogen after engagement with the glucose-regulated protein 78 induces autophagy in endothelial cells. Plasmin drives cellular extracellular matrix loss that induces programmed cell death or anoikis. Tumor cells by upregulating plasminogen activator inhibitor-1 suppress plasmin production. Now, they can escape anoikis and metastasize. The preparation of the premetastatic niche is prepared by exosomes, small membrane-bound extracellular vesicles. Exosomes carry fibrinolytic factors and thereby might be important for ECM preparation during the metastatic process. Finally, fibrinolytic factors and their receptors including uPAR and LRP1 are upregulated in cancer cells after myelosuppressive treatment and contribute to drug resistance. Targeting receptors of fibrinolytic factors including uPAR and LRP1 can be a strategy to overcome drug resistance.
  • 1.0K
  • 22 Sep 2021
Topic Review
Glycation-Associated Diabetic Nephropathy and Long Noncoding RNAs
The glycation of various biomolecules is the root cause of many pathological conditions associated with diabetic nephropathy and end-stage kidney disease. Glycation imbalances metabolism and increases renal cell injury. Numerous therapeutic measures have narrowed down the adverse effects of endogenous glycation, but efficient and potent measures are miles away. Recent advances in the identification and characterization of noncoding RNAs, especially the long noncoding RNAs (lncRNAs), have opened a mammon of new biology to explore the mitigations for glycation-associated diabetic nephropathy. Furthermore, tissue-specific distribution and condition-specific expression make lncRNA a promising key for second-generation therapeutic interventions.
  • 1.0K
  • 03 Nov 2022
Topic Review
Bionanomaterials against Gestational Diabetes Mellitus
Gestational diabetes mellitus (GDM) is the most frequent complication during pregnancy. This complex disease is characterized by glucose intolerance and consequent hyperglycemia that begins or is first diagnosed in pregnancy, and affects almost 7% of pregnant women. Previous reports have shown that GDM is associated with increased pregnancy complications and might cause abnormal fetal development. At present, treatments are not suitable for the prevention and management of these patients. As an alternative therapeutic opportunity and a leading scientific technique, nanotechnology has helped enlighten the health of these affected women. Theranostic nanomaterials with unique properties and small sizes (at least <100 nm in one of their dimensions) have been recently engineered for clinics and pharmaceutics. Reducing materials to the nanoscale has successfully changed their properties and enabled them to uniquely interact with cell biomolecules. Several biosensing methods have been developed to monitor glucose levels in GDM patients. 
  • 1.0K
  • 19 Oct 2021
Topic Review
Dietary Sulfur Amino Acid Restriction
Dietary sulfur amino acid restriction, also referred to as methionine restriction, increases food intake and energy expenditure and alters body composition in rodents, resulting in improved metabolic health and a longer lifespan. Among the known nutrient-responsive signaling pathways, the evolutionary conserved integrated stress response (ISR) is a lesser-understood candidate in mediating the hormetic effects of dietary sulfur amino acid restriction (SAAR). 
  • 1.0K
  • 18 Aug 2022
Topic Review
Melatonin in Early Nutrition
Melatonin, or N-acetyl-5-methoxytryptamine, is an indolamine derived from the amino acid tryptophan that is synthesized by the mammalian pineal gland in response to dark–light cycles. Environmental light is sensed by the inner retina (retinal ganglion cells), which sends neural signals not only to the visual areas of the brain but also to the pineal gland through complex neuronal connections. Melatonin is synthesized every evening in the pineal gland in response to the decrease in light.
  • 1.0K
  • 09 Aug 2021
Topic Review
Aging and Muscle Oxygen Utilization
The cardiovascular and skeletal muscle systems are intrinsically interconnected, sharing the goal of delivering oxygen to metabolically active tissue. Deficiencies within those systems that affect oxygen delivery to working tissues are a hallmark of advancing age. Oxygen delivery and utilization are reflected as muscle oxygen saturation (SmO2) and are assessed using near-infrared resonance spectroscopy (NIRS). SmO2 has been observed to be reduced by ~38% at rest, ~24% during submaximal exercise, and ~59% during maximal exercise with aging (>65 y).
  • 998
  • 19 Oct 2022
Topic Review
Insulin Structure, Function, and Detection in Biological Fluids
Insulin is a 5808 Da peptide hormone produced and secreted by the pancreas in response to increased levels of glucose in the circulation. It consists of a 21-amino-acid A chain and a 30-amino-acid B chain held together by two disulfide bonds and is responsible for regulating carbohydrate, lipid and protein metabolism by stimulating the uptake of glucose through insulin receptors found mainly in peripheral muscle, in adipocytes and in hepatocytes.
  • 998
  • 14 Jul 2023
Topic Review
Mitochondrial Dysfunction in MAFLD
Nonalcoholic fatty liver disease (NAFLD) has become an increasingly common diseases in Western countries and has become the major cause of liver cirrhosis or hepatocellular carcinoma (HCC) in addition to viral hepatitis in recent decades. Furthermore, studies have shown that NAFLD is inextricably linked to the development of extrahepatic diseases. In 2020, NAFLD was renamed metabolic dysfunction fatty liver disease (MAFLD) to show that its pathogenesis is closely related to metabolic disorders. And the interaction between mitochondrial dys-function and the liver–gut axis has also become a new point during the development of MAFLD.
  • 995
  • 02 Jan 2024
Topic Review
Impact of Bariatric Surgery on Adipose Tissue Biology
Bariatric surgery (BS) procedures are actually the most effective intervention to help subjects with severe obesity achieve significant and sustained weight loss. White adipose tissue (WAT) is increasingly recognized as the largest endocrine organ. Unhealthy WAT expansion through adipocyte hypertrophy has pleiotropic effects on adipocyte function and promotes obesity-associated metabolic complications. WAT dysfunction in obesity encompasses an altered adipokine secretome, unresolved inflammation, dysregulated autophagy, inappropriate extracellular matrix remodeling and insufficient angiogenic potential. 
  • 993
  • 08 Dec 2021
Topic Review
Pharmaceutical Drug and Metabolic Adaptions/Reprogramming in β-Cells
Islet inflammation in T1DM is characterized by leukocyte infiltrates, in particular macrophages and T-cells which damage β-cells by release of cytokines, ROS and NO and also activation of death-receptor-mediated death pathways and subsequent phagocytosis. Production of cytokines such as INF-γ, TNFα and IL-1β act in synergy to promote elevation in concentration and increase in activity of NADPH oxidase and iNOS consequently increasing the formation of products including ROS and NO, respectively. The mechanism of action of INF-γ, TNFα and IL-1β involves stimulation of transcription factors including NFκB (in mouse islet β-cells).
  • 986
  • 29 Mar 2022
Topic Review
Metabolic Mechanisms in Obesity-Related Childhood Asthma
Obesity-related asthma is a heterogeneous childhood asthma phenotype with rising prevalence. Observational studies identify early-life obesity or weight gain as risk factors for childhood asthma development.  Oxidative stress is a central pathogenetic process in obesity-related childhood asthma and is considered to drive other metabolic processes, including dysregulation of fatty acids, peripheral blood ketones, amino acid metabolism, and insulin resistance.
  • 981
  • 08 Mar 2023
Topic Review
Mitochondrial Ca2+ and Tumor Cell
Mitochondrial Ca2+ transport-related processes are involved in important biological processes of tumor cells including proliferation, metabolism, and apoptosis. In particular, MCU and its regulatory proteins represent a new era in the study of MCU-mediated mitochondrial Ca2+ homeostasis in tumors. 
  • 976
  • 30 Jun 2022
Topic Review
Dietary Intake and Energy Expenditure in Breast Cancer
Many breast cancer survivors (BCS) gain fat mass and lose fat-free mass during treatment (chemotherapy, radiation, surgery) and estrogen suppression therapy, which increases the risk of developing comorbidities. Whether these body composition alterations are a result of changes in dietary intake, energy expenditure, or both is unclear. Thus, we reviewed studies that have measured components of energy balance in BCS who have completed treatment. Longitudinal studies suggest that BCS reduce self-reported energy intake and increase fruit and vegetable consumption. Although some evidence suggests that resting metabolic rate is higher in BCS than in age-matched controls, no study has measured total daily energy expenditure (TDEE) in this population. Whether physical activity levels are altered in BCS is unclear, but evidence suggests that light-intensity physical activity is lower in BCS compared to age-matched controls. We also discuss the mechanisms through which estrogen suppression may impact energy balance and develop a theoretical framework of dietary intake and TDEE interactions in BCS. Preclinical and human experimental studies indicate that estrogen suppression likely elicits increased energy intake and decreased TDEE, although this has not been systematically investigated in BCS specifically. Estrogen suppression may modulate energy balance via alterations in appetite, fat-free mass, resting metabolic rate, and physical activity. There are several potential areas for future mechanistic energetic research in BCS (e.g., characterizing predictors of intervention response, appetite, dynamic changes in energy balance, and differences in cancer sub-types) that would ultimately support the development of more targeted and personalized behavioral interventions. 
  • 975
  • 11 Oct 2021
Topic Review
Thyroid Gland Homeostasis and TGF-β
Transforming growth factor beta (TGF-β), as a master regulator of immune response, is deeply implicated in the complex pathophysiology and development of autoimmune thyroid diseases.
  • 969
  • 06 Sep 2021
Topic Review
Glioblastoma Metabolomics
Glioblastoma (GBM), a grade IV glioma, continues to have one of the highest mortality rates among central nervous system tumors. Metabolomics is a particularly promising tool for the analysis of GBM tumors and potential methods of treating them, as it is the only “omics” approach that is capable of providing a metabolic signature of a tumor’s phenotype.
  • 968
  • 15 Jun 2021
Topic Review
Trans-Endothelial Fatty Acid Transport and Cardiac Metabolism/Contractile
The heart is a metabolic omnivore that combusts a considerable amount of energy substrates, mainly long-chain fatty acids (FAs) and others such as glucose, lactate, ketone bodies, and amino acids. There is emerging evidence that muscle-type continuous capillaries comprise the rate-limiting barrier that regulates FA uptake into cardiomyocytes. The transport of FAs across the capillary endothelium is composed of three major steps—the lipolysis of triglyceride on the luminal side of the endothelium, FA uptake by the plasma membrane, and intracellular FA transport by cytosolic proteins. In the heart, impaired trans-endothelial FA (TEFA) transport causes reduced FA uptake, with a compensatory increase in glucose use. In most cases, mice with reduced FA uptake exhibit preserved cardiac function under unstressed conditions. When the workload is increased, however, the total energy supply relative to its demand (estimated with pool size in the tricarboxylic acid (TCA) cycle) is significantly diminished, resulting in contractile dysfunction. The supplementation of alternative fuels, such as medium-chain FAs and ketone bodies, at least partially restores contractile dysfunction, indicating that energy insufficiency due to reduced FA supply is the predominant cause of cardiac dysfunction. 
  • 966
  • 20 Jan 2022
Topic Review
Kidney Disease in Diabetic Patients
Diabetic patients often present diabetic kidney disease (DKD), a burdensome complication that can be silent for years. The average time of onset of kidney impairment in diabetic patients is about 7–10 years. The clinical impact of DKD is dangerous not only for the risk of progression to end-stage renal disease and therefore to renal replacement therapies, but also because of the associated increase in cardiovascular events.
  • 963
  • 09 Jul 2021
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