16.5 Metabolic States of the Body

You eat periodically throughout the day; however, your organs, especially the brain, need a continuous supply of glucose. How does the body meet this constant demand for energy? Your body processes the food you eat both to use immediately and, importantly, to store as energy for later demands. If there were no method in place to store excess energy, you would need to eat constantly in order to meet energy demands. Distinct mechanisms are in place to facilitate energy storage, and to make stored energy available during times of fasting and starvation.

Nutrient Pools

Throughout the day, the body may either draw upon or add to its nutrient pools, or the current stockpile of amino acids, carbohydrates, and fats, depending on the needs of the body. These pools are interconvertable, meaning that one nutrient may be converted into another type, because their metabolic pathways are linked by certain intermediate molecules (Figure 16.5.1).

The amino acid pool includes all of the free amino acids within the body. Some of these amino acids will be used to build proteins that will later be lost, such as the keratin produced by cells of the epidermis in the skin; when those skin cells are sloughed off, their proteins are lost with them. The body replaces these lost amino acids through the diet or from breaking down proteins in other tissues; for this reason, the proteins within cells of the body (primarily skeletal muscle) function as a reservoir for amino acids. Free amino acids are available to be incorporated into new proteins within cells or form products derived from amino acids like certain neurotransmitters and hormones. If there are excess amino acids within the body, the liver converts some amino acids to glucose; in this process, the amino group is removed and converted to urea, which is excreted in urine. The rest of the deaminated amino acid can then be converted to glucose, which can then be turned into fat, stored as glycogen, or broken down for ATP.

For carbohydrates, the main storage molecule is glycogen, a polymer of glucose. Some cells, like skeletal muscle, maintain a stockpile of glycogen for the cell’s own use; when skeletal muscle breaks glycogen down into individual glucose molecules, those glucose molecules stay within the skeletal muscle cells to power ATP production. In other tissues, specifically the liver, the glucose released from glycogen breakdown is shuttled to the blood in order to keep blood glucose levels stable. Excess carbohydrates are converted to fats for long-term storage. Since carbohydrates are easily converted to fats, often the carbohydrate pool and the fat pool are considered together.

The fat pool is stored in the form of triglycerides, where one molecule of glycerol (a three-carbon alcohol) is attached to three fatty acids. Triglycerides are primarily stored within adipose tissue. When triglycerides are broken down to glycerol and fatty acids, these two products have different fates. The glycerol may be converted to glucose, but fatty acids can not be converted to glucose. Instead, fatty acids may be converted to acetyl CoA and broken down for ATP via the citric acid cycle; in the liver, acetyl CoA may also be used to produce cholesterol, a key component for cell membranes and the precursor to all steroid hormones. Free fatty acids may also be used by cells and incorporated into cell membranes.

The Absorptive State

The absorptive state, or the fed state, occurs after a meal when your body is digesting the food and absorbing the nutrients (anabolism exceeds catabolism). Digestion begins the moment you put food into your mouth, as the food is broken down into its constituent parts to be absorbed through the intestine. The digestion of carbohydrates begins in the mouth, whereas the digestion of proteins and fats begins in the stomach and small intestine. The constituent parts of these carbohydrates, fats, and proteins are transported across the intestinal wall and enter the bloodstream (sugars and amino acids) or the lymphatic system (fats). From the intestines, these systems transport them to the liver, adipose tissue, or muscle cells that will process and use, or store, the energy.

Depending on the amounts and types of nutrients ingested, the absorptive state can linger for up to 4 hours. The ingestion of food and the rise of glucose concentrations in the bloodstream stimulate pancreatic beta cells to release insulin into the bloodstream, where it initiates the absorption of blood glucose by liver hepatocytes, and by adipose and muscle cells. Once inside these cells, glucose is immediately converted into glucose-6-phosphate. By doing this, a concentration gradient is established where glucose levels are higher in the blood than in the cells. This allows for glucose to continue moving from the blood to the cells where it is needed. Insulin also stimulates glycogenesis, the storage of glucose as glycogen in the liver and muscle cells where it can be used for later energy needs of the body. Insulin also promotes the synthesis of protein in muscle. As you will see, muscle protein can be catabolized and used as fuel in times of starvation.

If energy is exerted shortly after eating, the dietary fats and sugars that were just ingested will be processed and used immediately for energy. If not, the excess glucose is stored as glycogen in the liver and muscle cells, or as fat in adipose tissue; excess dietary fat is also stored as triglycerides in adipose tissues.

Figure 16.5.2 summarizes the metabolic processes occurring in the body during the absorptive state.

The Postabsorptive State

The postabsorptive state, or the fasting state, occurs when the food has been digested, absorbed, and stored. You commonly fast overnight, but skipping meals during the day puts your body in the postabsorptive state as well. During this state, the body must rely initially on stored glycogen. Glucose levels in the blood begin to drop as it is absorbed and used by the cells. In response to the decrease in glucose, insulin levels also drop. Glycogen and triglyceride storage slows. However, due to the demands of the tissues and organs, blood glucose levels must be maintained in the normal range of 80 to 120 mg/dL. In response to a drop in blood glucose concentration, the hormone glucagon is released from the alpha cells of the pancreas. Glucagon acts upon the liver cells, where it inhibits the synthesis of glycogen and stimulates glycogenolysis, the breakdown of stored glycogen back into glucose. This glucose is released from the liver to be used by the peripheral tissues and the brain. As a result, blood glucose levels begin to rise. Gluconeogenesis will also begin in the liver to replace the glucose that has been used by the peripheral tissues.

After ingestion of food, fats and proteins are processed as described previously; however, the glucose processing changes a bit. The peripheral tissues preferentially absorb glucose. The liver, which normally absorbs and processes glucose, will not do so after a prolonged fast. The gluconeogenesis that has been ongoing in the liver will continue after fasting to replace the glycogen stores that were depleted in the liver. After these stores have been replenished, excess glucose that is absorbed by the liver will be converted into triglycerides and fatty acids for long-term storage. Figure 16.5.3 summarizes the metabolic processes occurring in the body during the postabsorptive state.

Blood glucose levels in the body are controlled by two major hormones: insulin and glucagon. These hormones are antagonistic, meaning that their effects are opposite one another. During the absorptive state, insulin is released due to several factors (Figure 16.5.4):

• Rising blood glucose levels and free amino acid levels stimulate the pancreas to release insulin.
• Enteroendocrine cells of the small intestine secrete glucose-dependent insulinotropic peptide (GIP) into the blood, which interact with receptors on beta cells to stimulate the release of insulin.
• The parasympathetic division of the autonomic nervous system stimulates insulin release during feeding.

Insulin binds to receptors on skeletal muscle, adipose, and liver cells, which promotes the insertion of glucose carrier proteins into the plasma membrane (Figure 16.5.5). With more glucose transport proteins embedded in the membrane, glucose is rapidly moved into the target cells for breakdown, glycogen synthesis, or conversion to fats for long-term storage.

As glucose is rapidly taken up by target cells, the pancreas detects the falling glucose levels and reduces insulin secretion in a classic example of negative feedback regulation.

Glucagon is an antagonist of insulin, so its pathway is in many ways the opposite of insulin. When blood glucose levels fall below normal in the postabsorptive state, glucagon is released from alpha cells in the pancreas. Glucagon directs the liver and skeletal muscle to break down the stored glycogen (glycogenolysis), adipose tissue and the liver to break down lipids (lipolysis), and the liver to produce glucose from amino acids or glycerol (gluconeogenesis). Combined, these actions help to raise blood glucose levels back to the normal range. Once blood glucose levels rise to normal, glucagon secretion decreases.

As shown in Figure 16.5.6, glucagon and insulin work together to maintain blood glucose levels within the normal homeostatic range of 80 to 120 mg/dL. Maintaining blood glucose levels within this range is important, as the brain almost exclusively uses glucose as its energy source.

References

American Diabetes Association. (n.d.). Commitment to health care access. https://diabetes.org/about-us/health-access-commitment

Centers for Disease Control and Prevention. (2024, May 15). Advancing health equity: Diabetes. U.S. Department of Health & Human Services. https://www.cdc.gov/diabetes/health-equity/index.html

Hassan, S., Gujral, U. P., Quarells, R. C., Rhodes, E. C., Shah, M. K., Obi, J., Lee, W. H., Shamambo, L., Weber, M. B., & Narayan, K. M. V. (2023, June 22). Disparities in diabetes prevalence and management by race and ethnicity in the USA: defining a path forward. Lancet. Diabetes & endocrinology 11(7), 509–524.

Peek, M. E., Cargill, A., & Huang, E. S. (2007, October). Diabetes health disparities: a systematic review of health care interventions. Medical care research and review: MCRR 64(5 Suppl), 101S–56S.

Image Descriptions

Figure 16.5.1. This flowchart diagram illustrates the integrated metabolic pathways connecting the three major macronutrients: proteins, carbohydrates, and fats. The diagram is organized into three vertical columns labeled at the top. The left column shows protein metabolism in purple boxes, starting with proteins breaking down into amino acids, which then convert to keto acids. The middle column depicts carbohydrate metabolism in blue boxes, showing a sequential pathway from glycogen to glucose to glyceraldehyde 3-phosphate to pyruvate, with lactate shown as a side pathway connected to pyruvate by bidirectional arrows. The right column represents fat metabolism in green boxes, showing triglycerides breaking down into glycerol and fatty acids. The diagram emphasizes metabolic integration through multiple connecting arrows between pathways. Glycerol and fatty acids connect to glyceraldehyde 3-phosphate via bidirectional arrows, showing how lipid breakdown can feed into glycolysis. Pyruvate serves as a central hub, converting downward to acetyl CoA (shown in an orange box). Acetyl CoA connects bidirectionally to both glycerol and fatty acids, demonstrating that acetyl CoA can be used to synthesize fats or derived from fat breakdown. Acetyl CoA also connects bidirectionally to ketone bodies (shown in a light blue box on the right), illustrating ketogenesis and ketone oxidation. At the bottom, acetyl CoA feeds into the citric acid cycle (shown in a pink box), which receives bidirectional arrows from keto acids, indicating that amino acid carbon skeletons can enter the cycle at various points. The citric acid cycle also connects back to ketone bodies. All arrows in the diagram are bidirectional, represented by thick dark blue lines with arrows on both ends, emphasizing that most metabolic pathways are reversible and that the body can interconvert these macronutrients based on metabolic needs. This comprehensive diagram illustrates how proteins, carbohydrates, and fats are not metabolized in isolation but are part of an integrated network that allows the body to adapt to different nutritional states and energy demands. [Return to Figure 16.5.1]

Figure 16.5.2. This diagram illustrates the absorptive state of metabolism, showing how the body processes and stores nutrients after a meal under the influence of insulin. A legend at the top left identifies symbols used throughout: purple circles for insulin, green circles for glucose, yellow triangles for lipids, and orange rectangles for amino acids. The process begins at the top (labeled 1) where digested nutrients enter the bloodstream from the intestines, causing blood sugar concentration to rise. A green arrow points downward to a blood vessel depicted in pink/coral, containing various nutrients represented by the colored symbols. Step 2 shows the pancreas, illustrated with detailed cellular structure, releasing insulin (indicated by a purple arrow) into the bloodstream in response to rising blood glucose levels. The text explains that insulin increases glucose uptake by all body cells, reducing blood glucose concentration back to homeostasis. The middle section shows a cross-section of a large blood vessel with nutrients distributed throughout, branching to supply three different tissue types shown below. The bottom portion of the diagram presents three parallel scenarios (3a, 3b, 3c) showing how different cell types respond to insulin during the absorptive state. Each scenario includes a detailed cell illustration above and a zoomed-in view of the cell membrane and interior below. Section 3a depicts liver cells with their characteristic detailed internal structure. The magnified view shows the cell membrane at the top with blood vessels above containing nutrients. Blue insulin receptor complexes are shown in the membrane facilitating glucose entry. Inside the cell (shown in green/olive), glucose is converted to glucose-6-phosphate, which then forms glycogen (depicted as branched chains of green circles) for storage. The diagram also indicates ketogenesis occurring. The caption explains that liver cells convert excess glucose to glycogen via glucose-6-phosphate, and amino acids are converted into ketone bodies that can later become acetyl CoA. Section 3b shows muscle cells, illustrated as elongated striated tissue in the upper image. The magnified view similarly shows insulin receptors in the membrane facilitating glucose uptake. Inside the muscle cell, glucose becomes glucose-6-phosphate and is stored as glycogen (green circles arranged in chains). The caption notes that amino acids are used to synthesize actin and myosin for muscle fiber rebuilding, with “Actin and myosin synthesis” labeled in the cell interior. Section 3c displays adipose cells, shown in the upper image as large cells filled with lipid droplets (yellow circles). The magnified view shows insulin receptors in the membrane, with the interior dominated by lipid storage depicted as numerous yellow triangles filling the green cytoplasm. The caption explains that adipose cells store excess lipids, increasing fat reserves. Green arrows beneath each cell type point downward to their respective magnified views, connecting the tissue-level organization to the cellular mechanisms. This comprehensive diagram demonstrates how insulin coordinates the storage of different nutrients in specialized tissues during the absorptive state following a meal. [Return to Figure 16.5.2]

Figure 16.5.3. This diagram illustrates the postabsorptive state of metabolism, showing how the body mobilizes stored energy reserves between meals when no nutrients are entering the bloodstream from the digestive system. A legend at the top left identifies symbols used throughout: purple circles for glucagon, green circles for glucose, yellow triangles for lipids, and orange rectangles for amino acids. The process begins at step 1, where the postabsorptive state is defined as a period when no nutrients enter the bloodstream from the digestive system. A blood vessel is depicted in coral/pink, initially appearing mostly empty. Step 2 shows the pancreas, illustrated with detailed cellular structure, releasing glucagon (indicated by a purple arrow) into the bloodstream in response to dropping blood sugar concentrations. The text explains that low glucose levels stimulate the pancreas to stop releasing insulin and instead release glucagon. The middle section shows a cross-section of a blood vessel now containing primarily glucagon (purple circles) with only occasional glucose molecules (green circles), reflecting the fasting state. The vessel branches to supply three different tissue types shown below. The bottom portion presents three parallel scenarios (3a, 3b, 3c) demonstrating how different cell types respond to glucagon during the postabsorptive state. Each scenario includes a tissue-level illustration above and a magnified cellular view below. Section 3a depicts liver cells with their characteristic complex internal architecture. The magnified view shows the cell membrane at top with blood vessels above containing mostly glucagon. Blue glucagon receptor complexes span the membrane. Inside the cell (shown in green/olive), stored glycogen (depicted as branched chains of green circles labeled “Glucose-6-phosphates”) is being broken down through glycogenolysis. Arrows show glucose molecules being released into the bloodstream. The diagram also indicates ketone oxidation occurring, with orange rectangles (amino acids) and yellow triangles (lipids) being processed. The caption explains that glycogenolysis releases glucose into the blood, returning blood glucose concentrations to homeostasis, while ketone oxidation releases lipids and additional glucose that body cells can use to generate ATP. Section 3b shows muscle cells, illustrated as striated tissue in the upper image. The magnified view displays glucagon receptors in the membrane with stored glycogen chains (green circles labeled “Glucose-6-phosphates”) in the cytoplasm being mobilized. An orange rectangle representing an amino acid is shown being released. The caption notes that muscle cells release glucose into the blood, returning blood glucose concentrations to homeostasis, and that catabolized amino acids from muscle proteins can generate ATP after undergoing ketogenesis and ketone oxidation in the liver, with “Actin and myosin catabolism” labeled in the cell. Section 3c displays adipose cells, shown in the upper image as cells with large lipid droplets (yellow circles). The magnified view shows glucagon receptors in the membrane with the interior containing lipid storage depicted as numerous yellow triangles. Arrows indicate lipids being mobilized and released. The caption explains that adipose cells release stored lipids, which can be used to generate glucose, ketone bodies, or ATP. Teal/turquoise arrows beneath each cell type point downward to their respective magnified views, connecting tissue organization to cellular mechanisms. This comprehensive diagram demonstrates how glucagon orchestrates the mobilization of energy stores from different tissues during fasting, maintaining blood glucose homeostasis by breaking down glycogen in liver and muscle, releasing lipids from adipose tissue, and even catabolizing proteins when necessary to provide fuel for the body between meals. [Return to Figure 16.5.3]

Figure 16.5.4. This diagram illustrates the various factors that regulate insulin secretion from the pancreas. At the center is a beige circular region containing an illustration of the pancreas, depicted in orange/tan with its characteristic lobulated structure. Small orange dots emanate from the pancreas, representing insulin being released into the bloodstream. Surrounding the central pancreas are six circles connected by arrows, divided into two categories. The upper portion shows three light blue circles containing stimulatory factors that promote insulin release, indicated by blue arrows pointing toward the pancreas. These stimulatory factors are: high GIP (glucose-dependent insulinotropic polypeptide) at the top, parasympathetic stimulation on the left, and high glucose and amino acids on the right. The lower portion shows three pink circles containing inhibitory factors that suppress insulin release, indicated by red bars (blunt-ended lines) pointing toward the pancreas. These inhibitory factors are: epinephrine on the left, infection at the bottom, and low glucose on the right. This diagram effectively demonstrates how insulin secretion is regulated by a balance of promoting and inhibiting signals, with metabolic factors like nutrient levels, hormonal signals like GIP and epinephrine, neural input from the parasympathetic nervous system, and physiological stressors like infection all playing roles in maintaining blood glucose homeostasis. [Return to Figure 16.5.4]

Figure 16.5.5. This diagram illustrates the molecular mechanism by which insulin facilitates glucose entry into cells through a four-step process. The image shows a cross-section of a cell membrane (depicted as a gray double layer) with various molecular components. Step 1, labeled “Insulin binds to receptor” at the top left, shows insulin molecules (represented as light blue circles) approaching and binding to an insulin receptor (shown as a dark blue Y-shaped protein structure) embedded in the cell membrane. The receptor has two circular binding domains at its base within the membrane. Step 2, labeled “Signal cascade,” shows a black arrow extending downward from the activated receptor into the cell’s interior, indicating that receptor binding triggers intracellular signaling pathways. These pathways are represented by curved gray lines resembling tubular structures or vesicles within the cytoplasm. Step 3, labeled “Exocytosis,” depicts multiple purple oval-shaped vesicles containing GLUT-4 glucose transporter proteins (labeled “GLUT-4”) moving along the internal membrane structures. Black arrows indicate these vesicles are trafficking toward the cell membrane in response to the insulin signal. Step 4, labeled “Glucose entry permitted” at the top right, shows the final result where GLUT-4 transporters have been inserted into the cell membrane. Two GLUT-4 proteins are now embedded in the membrane, shown as purple oval shapes with darker centers. Dark red/maroon circles representing glucose molecules are shown above the membrane, with black arrows indicating they can now pass through the GLUT-4 transporters into the cell. This comprehensive diagram demonstrates how insulin signaling causes the translocation of glucose transporters from intracellular storage vesicles to the plasma membrane, enabling cells to take up glucose from the bloodstream for energy production or storage. [Return to Figure 16.5.5]

Figure 16.5.6. This diagram illustrates the hormonal regulation of blood glucose homeostasis through opposing actions of insulin and glucagon in a negative feedback system. The diagram features two main organs: the liver (shown in pink/mauve on the left) and the pancreas (shown in beige/tan on the right). Two main pathways are depicted using purple and teal arrows. The upper pathway, shown in purple, begins with “High blood glucose” in a purple box at the top right. A purple arrow labeled “Promotes insulin release” points from this box to the pancreas. From the pancreas, a purple arrow labeled “Insulin” extends to the liver, where it “Stimulates glycogen formation,” shown by a circular pathway converting glucose to glycogen within the liver. Additional purple arrows from the insulin pathway point to “Tissue cells” (represented by three small beige squares at the bottom center) with the label “Stimulates glucose uptake from blood.” These pathways converge at the bottom left where arrows indicate “Lowers blood glucose,” connecting via a dotted purple line to a teal box labeled “Low blood glucose.” The lower pathway, shown in teal, begins with “Low blood glucose” in a teal box at the bottom right. A teal arrow labeled “Promotes glucagon release” points from this box to the pancreas. From the pancreas, a teal arrow labeled “Glucagon” extends to the liver, where it “Stimulates glycogen breakdown,” shown by the circular pathway converting glycogen back to glucose. The teal pathway continues upward with an arrow labeled “Raises blood glucose,” connecting via a dotted teal line to the “High blood glucose” box at the top. Within the liver, black arrows show the reversible conversion between glycogen and glucose. This cyclical diagram demonstrates how the body maintains blood glucose within a narrow range: when blood glucose is high, insulin promotes glucose storage and uptake, lowering blood glucose levels; when blood glucose is low, glucagon promotes glucose release from glycogen stores, raising blood glucose levels back to homeostasis. [Return to Figure 16.5.6]

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