Main Organs Involved in Glucose Metabolism

*Laura Lema-Pérez*

## **Abstract**

Sugar, or technically known as glucose, is the main source of energy of all cells in the human body. The glucose homeostasis cycle is the mechanism to maintain blood glucose levels in a healthy threshold. When this natural mechanism is broken, many metabolic disorders appear such as diabetes mellitus, and some substances of interest, like glucose, are out of control. In the mechanism to maintain blood glucose, several organs are involved but the role of most of them has been disregarded in the literature. In this chapter, the main organs involved in such a mechanism and their role in glucose metabolism are described. Specifically, the stomach and small intestine, organs of the gastrointestinal system, are the first to play an important role in the regulatory system, because it is where carbohydrates are digested and absorbed as glucose into the bloodstream. Then glucose as a simple substance goes to the liver to be stored as glycogen. Glucose storage occurs due to the delivery of hormones from the pancreas, which produces, stores, and releases insulin and glucagon, two antagonistic hormones with an important role in glucose metabolism. The kidneys assist the liver in insulin clearance in the postprandial state and gluconeogenesis in the post absorptive state. Physiological aspects and the detailed role of every organ involved in glucose metabolism are described in this chapter.

**Keywords:** glucose metabolism, homeostasis, diabetes mellitus

### **1. Introduction**

Glucose is contained in foods rich in carbohydrates like bread, potatoes, rice, and fruits. It can be as a simple molecule, sugar, or complex molecules, carbohydrates. Although carbohydrates are more abundant in the diet, they are digested to be converted into glucose molecules to be absorbed in the gut. Previously to be absorbed, stomach and small intestine play an important role in digestion every particle ingested. First, food reaches the stomach after being chewed and swallowed from mouth. The digestion of carbohydrates begins in the mouth with saliva while chewing, but continues in the small intestine because the acidic pH of the stomach inactivates the amylase enzyme that is responsible for breaking them down. In the small intestine, the digestion of carbohydrates ends to be absorbed, through the enterocytes, into the blood. Once the glucose molecules are absorbed into the bloodstream, they reach the liver by traveling through the portal system. In the liver, they are partially stored as glycogen by the action of the insulin previously released in the pancreas. The rest of the glucose continues in the circulation, reaches the heart and all tissues and organs. Insulin concentrations are proportional to glucose concentrations due to this hormone make enter the glucose into the cells. In fact, insulin concentrations released by the pancreas are usually higher than glucose concentrations in blood. In this sense, the kidneys regulate glucose and insulin concentrations once these molecules reach them. Insulin is clearance in both, liver and kidneys, while glucose is produced from non-carbohydrates precursors in the postprandial state to compensate for the insulin excess in the blood. On the other hand, during a fasting period or a post-absorptive state, glucagon is released into the bloodstream by the pancreas and achieves the liver to dephosphorylate the glycogen into glucose to keep blood glucose levels in the healthy threshold. As can be seen from everything mentioned above, blood glucose levels can be set at the desired threshold thanks to the joint work between all the organs of the human body, where they all play an important role in this regulatory system. Next sections.

#### **2. Importance of glucose in the human body**

Cells of the tissues in the human body use glucose, the simplest of the carbohydrates, as the main source of energy to carry out their metabolic processes. Despite this, glucose consumption should be moderate because an excess can trigger multiple metabolic disorders that can even be chronic. Carbohydrates start to be processed immediately they are ingested, i.e., its digestion begins in the mouth with the amylase in the saliva. Then, ingested food travels throughout the esophagus to the stomach. In the stomach, the enzyme amylase is inactivated due to acidic pH, so carbohydrates cannot continue to digest. Other nutrients such as protein and fat are partially digested in the stomach, about 5% and 20%, respectively [1]. Once the ingested food has the appropriate rheological properties, it passes through the pylorus to reach the duodenum, the first part of the small intestine. In the duodenum, the bile produced from and gallbladder, is released to digest fats. The digestion of all nutrients ends in the small intestine by an additional intervention of the pancreas with the release of both pancreatic enzymes such as amylases, lipases, and proteases, and hormones such as insulin and glucagon. The molecules produced during digestion are absorbed by the enterocytes into the bloodstream. The rest of the food that is not absorbed in the small intestine passes into the colon.

Once glucose is in the systemic circulation, insulin hormone helps it to enter into the cells. Inside the cells, glucose is broken down to produce adenosine triphosphate (ATP) molecules by means of glycolysis. ATP are energy-rich molecules that power numerous cellular processes. Therefore, a constant supply of glucose from the blood to the cells must be ensured. Negative feedback systems [2] are responsible to ensure blood glucose concentrations in a normal range of 70 to 110 milligrams of glucose per deciliter of blood ( *mg dL* / ) [3]. Negative feedback systems are mechanisms that perceive changes in the human body and activate mechanisms that reverse the changes to restore conditions to their normal levels. Furthermore, negative feedback systems are critically important in glucose homeostasis in the maintenance of relatively constant internal conditions. In this regard, negative feedback systems make the pancreas to produce and release more insulin when there is an excess glucose consumption. This fact, maintained over time, can cause disruptions in glucose homeostasis lead to potentially life-threatening such as insulin resistance and diabetes mellitus.

The body also use other sources of energy such as amino acids (building blocks of proteins) and fats. However, despite these alternative energy sources, a minimum level of glucose in the blood must be ensured mainly for the metabolic activities of the brain and nervous system. Glucose is the main source of fuel for the brain and nervous system. Nerve cells and chemical messengers need glucose to process information. On the other hand, the liver and muscles can store the leftover glucose in little bundles

**123**

source in the cells [4].

*Main Organs Involved in Glucose Metabolism DOI: http://dx.doi.org/10.5772/intechopen.94585*

**3. The glucose regulation cycle**

called glycogen once the human body has used all the energy it needs. Glycogen works as a reserve fuel to be used during post-absorptive or fasting periods. Glycogenolysis is the biochemical process for converting glycogen to glucose in the liver. This process, together with the absorption of glucose in the small intestine after an ingested meal and the hepatic and renal gluconeogenesis, are the main factors to increase the levels of glucose in the blood. Sometimes, glucose levels in the blood can also go sky high under stressful conditions. Also, the High-Intensity Interval Training (HIIT) type of exercise is acknowledged to trigger (not completely understood) mechanisms able to rise the blood glucose levels. Contrary, the transport of the glucose into the cells by insulin action, physical exercise, and sometimes glycosuria (a condition characterized by an excess of sugar in the urine occurring under abnormal events when glucose homeostasis is impaired) are the main factors able to decrease blood glucose levels. Regardless of the condition, the human body is designed to keep the level of glucose in the bloodstream in healthy levels. However, when the glucose homeostasis is broken, diseases such as diabetes mellitus appear and persistent high blood glucose can lead generating acute complications such as diabetic ketoacidosis, retinopathy, diabetic nephropathy, neuropathy, and cardio-cerebrovascular disease. How does the body for regulating glucose levels in the blood? The next section introduces the glucose regulation cycle in detail and the role of every organ that is involved.

Glucose homeostasis is the mechanism able to maintain the blood glucose levels near the range of 70 / *mg dl* to 110 / *mg dL* by the action of a complex interplay among organs, hormones, metabolic-systems, and neural control mechanisms. As mentioned above, glucose is the main source of energy by allowing essential cellular processes such as respiration, tissue repair, cell multiplication, to be carried out, among others. Production and release of pancreatic hormones, mainly insulin and glucagon, ensures the glucose regulation in the blood [3]. **Figure 1** shows how the human body maintains glucose levels in a specific physiological range. Once carbohydrates nutrients are ingested and enter the digestive tube, several enzymes begin to work to digest macronutrients, e.g., amylases trigger for polysaccharide break-

down. In this way, polysaccharides are converted into monosaccharides, smaller molecules able to be absorbed by enterocytes in the small intestine. Monosaccharides absorption leads to increased blood glucose levels in the bloodstream. Simultaneously to this process, the incretin effect also occurs in which β-cells in the pancreas are stimulated by the action of GIP and GLP-1 hormones. Stimulation of β-cells drives the production and release of insulin, which increases the amount of GLUT4 glucose transporters in the cell membranes of different tissues [3]. Blood glucose concentrations also stimulate insulin production, and the hormones GIP and GLP-1 modulate it. As mentioned before, there are specialized molecules called GLUT to transport glucose from the blood into cells through cell membranes by diffusion. In this way, Excess glucose is eliminated from the blood, decreasing it. This process is represented in the figure with the plus sign. Therefore, glucose is transported within muscle and adipocytes cells, hepatocytes, neurons, etc., to be used as a source of energy. The liver is also answerable to sense blood glucose concentrations coming from the portal system and systemic circulation. In the liver, enzymes known as glucokinase are responsible to sense glucose amount, stimulate its diffusion through the hepatocytes, and simultaneously produce glycogen from glucose excess. Glycogen is a multibranched polysaccharide of glucose used as glucose storage to be used during fasting periods as an energy

#### *Main Organs Involved in Glucose Metabolism DOI: http://dx.doi.org/10.5772/intechopen.94585*

*Sugar Intake - Risks and Benefits and the Global Diabetes Epidemic*

play an important role in this regulatory system. Next sections.

that is not absorbed in the small intestine passes into the colon.

Once glucose is in the systemic circulation, insulin hormone helps it to enter into the cells. Inside the cells, glucose is broken down to produce adenosine triphosphate (ATP) molecules by means of glycolysis. ATP are energy-rich molecules that power numerous cellular processes. Therefore, a constant supply of glucose from the blood to the cells must be ensured. Negative feedback systems [2] are responsible to ensure blood glucose concentrations in a normal range of 70 to 110 milligrams of glucose per deciliter of blood ( *mg dL* / ) [3]. Negative feedback systems are mechanisms that perceive changes in the human body and activate mechanisms that reverse the changes to restore conditions to their normal levels. Furthermore, negative feedback systems are critically important in glucose homeostasis in the maintenance of relatively constant internal conditions. In this regard, negative feedback systems make the pancreas to produce and release more insulin when there is an excess glucose consumption. This fact, maintained over time, can cause disruptions in glucose homeostasis lead to potentially life-threatening such as insulin resistance

The body also use other sources of energy such as amino acids (building blocks of proteins) and fats. However, despite these alternative energy sources, a minimum level of glucose in the blood must be ensured mainly for the metabolic activities of the brain and nervous system. Glucose is the main source of fuel for the brain and nervous system. Nerve cells and chemical messengers need glucose to process information. On the other hand, the liver and muscles can store the leftover glucose in little bundles

**2. Importance of glucose in the human body**

concentrations released by the pancreas are usually higher than glucose concentrations in blood. In this sense, the kidneys regulate glucose and insulin concentrations once these molecules reach them. Insulin is clearance in both, liver and kidneys, while glucose is produced from non-carbohydrates precursors in the postprandial state to compensate for the insulin excess in the blood. On the other hand, during a fasting period or a post-absorptive state, glucagon is released into the bloodstream by the pancreas and achieves the liver to dephosphorylate the glycogen into glucose to keep blood glucose levels in the healthy threshold. As can be seen from everything mentioned above, blood glucose levels can be set at the desired threshold thanks to the joint work between all the organs of the human body, where they all

Cells of the tissues in the human body use glucose, the simplest of the carbohydrates, as the main source of energy to carry out their metabolic processes. Despite this, glucose consumption should be moderate because an excess can trigger multiple metabolic disorders that can even be chronic. Carbohydrates start to be processed immediately they are ingested, i.e., its digestion begins in the mouth with the amylase in the saliva. Then, ingested food travels throughout the esophagus to the stomach. In the stomach, the enzyme amylase is inactivated due to acidic pH, so carbohydrates cannot continue to digest. Other nutrients such as protein and fat are partially digested in the stomach, about 5% and 20%, respectively [1]. Once the ingested food has the appropriate rheological properties, it passes through the pylorus to reach the duodenum, the first part of the small intestine. In the duodenum, the bile produced from and gallbladder, is released to digest fats. The digestion of all nutrients ends in the small intestine by an additional intervention of the pancreas with the release of both pancreatic enzymes such as amylases, lipases, and proteases, and hormones such as insulin and glucagon. The molecules produced during digestion are absorbed by the enterocytes into the bloodstream. The rest of the food

**122**

and diabetes mellitus.

called glycogen once the human body has used all the energy it needs. Glycogen works as a reserve fuel to be used during post-absorptive or fasting periods. Glycogenolysis is the biochemical process for converting glycogen to glucose in the liver. This process, together with the absorption of glucose in the small intestine after an ingested meal and the hepatic and renal gluconeogenesis, are the main factors to increase the levels of glucose in the blood. Sometimes, glucose levels in the blood can also go sky high under stressful conditions. Also, the High-Intensity Interval Training (HIIT) type of exercise is acknowledged to trigger (not completely understood) mechanisms able to rise the blood glucose levels. Contrary, the transport of the glucose into the cells by insulin action, physical exercise, and sometimes glycosuria (a condition characterized by an excess of sugar in the urine occurring under abnormal events when glucose homeostasis is impaired) are the main factors able to decrease blood glucose levels.

Regardless of the condition, the human body is designed to keep the level of glucose in the bloodstream in healthy levels. However, when the glucose homeostasis is broken, diseases such as diabetes mellitus appear and persistent high blood glucose can lead generating acute complications such as diabetic ketoacidosis, retinopathy, diabetic nephropathy, neuropathy, and cardio-cerebrovascular disease. How does the body for regulating glucose levels in the blood? The next section introduces the glucose regulation cycle in detail and the role of every organ that is involved.
