Metabolism and metabolic disorders: glucose modulation, cardiac function, and mitochondria
What comes to mind when you think about “
metabolism”? One may claim to have a “fast metabolism” or a “slow metabolism,” but what does this mean? Metabolism can be simply defined as the chemical processes within a living organism to maintain life. Such chemical reactions can aid in nutrient digestion, stimuli response, and waste elimination. Despite the simplicity of the definition, metabolism is highly complex. Scientists study metabolic pathways to reveal the nuances of metabolism and how metabolic regulation is vital to facilitate normal biological processes to understand this complexity. Although there are millions of metabolic pathways, this TechNote will focus on three examples of metabolic pathways and how to study them: the modulation of glucose levels, cardiac function, and mitochondrial function. The healthy progression of these pathways is critical for human health, and any disruption can result in the pathogenesis of the metabolic disease. Metabolic disease affects over 66 million Americans and over 1 billion people worldwide while costing the healthcare industry billions of dollars a year (5, 6). In addition, the emotional burden on patients and their families is enormous. Therefore, we must continue to study metabolism in healthy and diseased contexts, specifically understanding what drives these metabolic pathways to develop treatments and prevention methods against metabolic disease.
Since glucose is a primary energy source for cells, modulation of glucose levels is critical for healthy energy consumption and ATP production. Too much or too little glucose in the bloodstream can result in metabolic diseases such as type 2 diabetes and hypoglycemia, respectively (Figure 1A, A’). The two primary molecular regulators of glucose modulation are
insulin and glucagon (4). Both insulin and glucagon are hormones secreted in response to an influx/efflux of glucose. Disruptions in the secretion or activity of either insulin or glucagon are common factors contributing to metabolic disease; therefore, understanding these hormones in the context of glucose modulation can shed light on metabolic diseases caused by their dysfunction. Detecting hormone levels in complex biological matrices such as serum, plasma, or tissue culture media has historically been inefficient and challenging due to the high level of interfering compounds. However, advancements in
ELISA technology have allowed researchers to quantify hormone levels such as insulin and glucagon in large dynamic ranges with high sensitivity. Understanding the levels of these specific analytes in different biological frameworks (genetic background, diet, and lifestyle factors) is critical toward developing therapeutic interventions against metabolic diseases such as type 2 diabetes and hypoglycemia and overall improve human health.
Metabolic pathways also regulate cardiac function. When these metabolic pathways are disrupted, metabolic diseases affecting cardiac function can develop (Figure 1B, B’). For example, cardiac infarction, atherosclerosis, and hypertension are metabolic diseases that arise from disrupted cardiac metabolism. A putative metabolic driver of cardiac function is
adiponectin(6), a hormone predominantly secreted from adipose tissue that protects cardiovascular tissues under stress conditions via inhibition of pro-inflammatory and hypertrophic responses. Adiponectin is often dysregulated in humans with cardio-metabolic diseases (6). Thus, gaining a deeper understanding of adiponectin and cardio-metabolic regulation is key for studying these pathologies and improving treatment and prevention options for
cardio-metabolic diseases.
Mitochondria are the site of most metabolic reactions. Human cells can harbor thousands of mitochondria, generating 90% of the energy we need to survive. Therefore, when mitochondrial function is disrupted, it can result in metabolic disease (Figure 1C, C’). For example, some mitochondrial diseases can affect oxidative phosphorylation and increase oxidative stress, which can alter mitochondrial membrane potential (MMP) and contribute to the development of neurodegenerative pathologies (7). The disruption of MMP is associated with the opening of the mitochondrial permeability transition pores, initiating the release of cytochrome C into the cytosol and triggering
apoptosis.
Furthermore, certain drugs can compromise MMP, thus contributing to metabolic disease. Therefore, understanding the parameters for healthy mitochondrial membrane potential and disrupted mitochondrial membrane potential is instrumental in identifying the etiology and pathogenesis of metabolic diseases. Sensitive molecular
tests to assess changes in MMP are tools to investigate the relationship between MMP and metabolic disease.
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Figure 1. Metabolic pathways at homeostasis vs. disruption
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Figure 1: (A) Glucose modulation is metabolically regulated, specifically the balance between insulin and glucagon release to facilitate healthy blood glucose levels. (A’) When insulin and glucagon are dysregulated, unhealthy blood glucose levels and metabolic diseases such as type 2 diabetes and hypoglycemia result. (B) Cardiac function is metabolically regulated via adiponectin release from adipose tissue. Adiponectin inhibits inflammation and hypertrophy of cardiac tissue contributing to cardiovascular health. (B’) Aberrant adiponectin release can increase cardiac inflammation, which leads to cardiometabolic diseases such as atherosclerosis, hypertension, and cardiac infarction. (C) Mitochondria are significant players in metabolic regulation and cellular health. The electron transport chain is essential for oxidative phosphorylation, redox reactions, ATP production, and healthy cellular respiration. (C’) Certain medications and free radicals can damage mitochondria, resulting in increased oxidative stress, disrupted MMP, and apoptosis. These pathologies can contribute to metabolic diseases such as neurodegeneration and mitochondrial disease. (Figure created using Biorender.com and partially adapted from “Electron Transport Chain” by BioRender.com (2021). Retrieved from w
https://app.biorender.com/biorender-templates).
How do we study metabolic disorders?
To study metabolic disease, we must identify tests to detect and quantify the drivers of these metabolic pathways. Enzo has been your valued partner in biomedical research for several decades and is here to provide you with the highest quality kits, reagents, and scientific expertise to further your
metabolic research. For example, detecting insulin and glucagon to understand glucose regulation will be foundational for therapeutic interventions. Quantifying adiponectin will provide valuable insight into cardio-metabolic diseases, and assaying for mitochondrial membrane potential increases our understanding of mitochondrial dynamics, leading to advanced clinical treatments.
Insulin can be an indicator of many other diseases, making it a suitable analyte to test for when studying a variety of conditions. For example, Haloul et al. showed that increased insulin levels in the human plasma directly correlated with increased homocysteine and low folate and vitamin B12 in obese populations. These metrics were significantly correlated with markers of cardiovascular inflammation such as C-reactive protein (CRP) and nitric oxide (NO) sensitivity. Revealing that together, insulin, homocysteine, and folate levels can be used as independent predictors of vascular dysfunction in morbidly obese individuals. Haloul et al. utilized Enzo’s
Insulin ELISA kit to measure plasma insulin levels as well as Enzo’s
Nitric Oxide detection kit to reveal the relationship between these biomarkers and demonstrate that they are predictors of metabolic disease (2).
As highlighted in this TechNote so far, another early biomarker of metabolic disease is adiponectin. Almeida-Pititto et al. demonstrated this by showing that the increase of leptin and decrease of adiponectin levels in humans correlates with larger neck circumference resulting in increased risk for insulin resistance and coronary artery calcium severity (1). This study relied on Enzo’s
Adiponectin ELISA kit to quantify adiponectin levels in 807 individuals.
Enzo also offers a comprehensive portfolio of products to study mitochondrial dynamics in metabolic regulation. For example, the
MITO-ID® Membrane potential detection kit is the only assay on the market that monitors active status using a simple mix-and-read, no-wash protocol. Researchers in the UK trusted this kit to investigate the effect of altered oxygen conditions in the placenta on fetal brain development. Overall, they discovered a link between compromised MMP and hypoxia to stimulate the release of factors that increase astrocyte number and decrease process length in brain cells, potentially contributing to the pathogenesis of mental disorders later in life (3).
Taken together, Enzo offers countless state-of-the-art scientific reagents and kits to ensure your research progresses forward and as we elevate human health together. Do you need help designing, analyzing, or troubleshooting your metabolism research project? The scientists at Enzo Life Sciences are eager to help you succeed. Contact our
technical service team to get started!
