**3. The glucose regulation cycle**

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 breakdown. 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 source in the cells [4].

**Figure 1.** *The glucose homeostasis in the human body.*

During fasting periods, glucose levels in the blood decrease causing inhibition of insulin production in the pancreas by the action of hormones known as catecholamines [4]. Consequently, α-cells in the pancreas are stimulated to produce glucagon hormone that acts antagonistically to insulin. Glucagon makes a function on the different hepatocyte receptors triggering both the action of the phosphorylase enzyme and the glycogenolysis process. Glycogenolysis is the process in which glycogen is converted into glucose to increase blood glucose levels and recover the lack of glucose, setting its concentrations in the desired levels [5]. This is symbolized in **Figure 1** by the minus sign.

*Diabetes Mellitus* is a condition appearing when the glucose homeostasis is broken, that is, plasma glucose levels are no longer maintained at desired levels. This is mainly due to a deficit in the production of insulin from the pancreatic β-cells or from a resistance to the action of the produced insulin.

#### **4. Main organs involved in glucose homeostasis**

Although some organs need fatty acids to carry out their metabolic processes, most tissues in the human body use glucose as their main source of energy. Good glucose utilization depends on keeping blood glucose levels within range at all times and on the proper functioning of the glucose homeostatic mechanism. Several complementary physiological processes are involved in the glucose homeostatic mechanism. The gastrointestinal tract is responsible to produce and absorb glucose, the liver carries out biochemical reactions such as glycogenolysis, glycolysis, and gluconeogenesis, the kidneys filter, reabsorb, and in some cases excrete glucose,

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

**4.1 Pancreas**

bloodstream:

insulin [7],

α

γ

somatostatin [7], and

membrane into the

and they also produce glucose from non-carbohydrate precursors. The role of the

The pancreas is a special organ because has both endocrine and exocrine functions. Exocrine functions consist of the production and secretion of digestive enzymes whereas endocrine functions include production and secretion of hormones. This chapter is primarily focused in the endocrine function given the crucial role on glucose homeostasis. Endocrine component of the pancreas consists of clustered cells forming the so-called islets of Langerhans. Islets of Langerhans are small island-shaped structures within exocrine pancreatic tissue representing only 1–2% of the entire organ [6]. The pancreatic islet endocrine cells include five different types that produce and release important hormones directly into the

β

play an essential role in the regulation of the blood glucose levels are insulin, which acts to lower it, and glucagon, which acts to raise it [10]. The balanced antagonistic action between them, maintain the glucose concentrations within the narrow range of 4–6 *mM* (70 to 110 *mg dL* / ) [6]. However, both hormones are inhibited by somatostatin [11]. Production and secretion of the hormones by pancreatic cells are stimulated by external signals such as nutrients intake, fasting, or stress. Blood glucose levels decrease during periods of rest such as sleep, between meals, or

glycogenolysis and gluconeogenesis processes. Unlike, in postprandial state, i.e.,

blood glucose levels via glycogenesis [12–14]. Insulin is released on demand but is produced and stored in large, dense-core vesicles that are recruited near the plasma

insulin is readily available to upcoming stimuli [15]. Glucose is the main signal to release insulin from the pancreas, but free fatty acids and amino acids can increase glucose-induced insulin secretion through the so-called incretin effect. As before mentioned, the incretin effect is originated in the intestinal tract (mainly duode-

as C-peptide [16], in an equimolar ratio, into the bloodstream.

some insulin states that are difficult to measure [24].

Insulin is a protein made up of 51 amino acids and when produced, it is first synthesized as a single polypeptide known as preproinsulin. Preproinsulin is an insulin gene encoded in 110 amino acids that are then processed into proinsulin. Proinsulin undergoes maturation into active insulin through the action of two different types of cells. One of them cleaves at 2 positions, releasing insulin and a fragment known

Insulin is released from β-cells in the pancreas in two phases, first one is triggered

in response to glucose levels and second one is triggered independently of sugar. Glucose and insulin in the bloodstream work together to avoid glucose from going out of range. Thus, Glucose is removed from the circulation thanks to the ability of insulin to cause insulin-dependent tissues to take up glucose [17–19]. Additionally, insulin promotes lipogenesis [20, 21], and the incorporation of amino acids into proteins [22] when it is in high concentrations. Different at low concentrations, which produce lipolysis in adipocytes, releasing free fatty acids by stimulating the use of lipids over glucose to satisfy energy needs at rest [23]. The release of insulin from β-cells is tightly regulated and exactly satisfies the metabolic demand for caloric nutrients in the body [16, 23]. Regarding C-peptide, it has been important to follow



δ




α


β


main organs involved in the glucose regulation cycle is described below.


ε

during fasting periods. In these cases, pancreatic

after a meal ingestion, insulin is released from

β

num) once the food is ingested.

and they also produce glucose from non-carbohydrate precursors. The role of the main organs involved in the glucose regulation cycle is described below.
