21.2 How Hormones Regulate Blood Glucose Levels

Regulation of Blood Glucose Levels by Glucagon

When blood glucose levels decline below normal levels, for example between meals or when glucose is utilized rapidly during exercise, the hormone glucagon is released from the alpha cells of the pancreas. Glucagon raises blood glucose levels, eliciting what is called a hyperglycemic effect, by stimulating the breakdown of glycogen to glucose in skeletal muscle cells and liver cells in a process called glycogenolysis. Glucose can then be utilized as energy by muscle cells and released into circulation by the liver cells (Figure 1). Glucagon also stimulates absorption of amino acids from the blood by the liver, which then converts them to glucose. This process of glucose synthesis is called gluconeogenesis. Glucagon also stimulates adipose cells to release fatty acids into the blood. These actions mediated by glucagon result in an increase in blood glucose levels to normal homeostatic levels. Rising blood glucose levels inhibit further glucagon release by the pancreas via a negative feedback mechanism.

Figure 1. Regulation of blood glucose levels by glucagon. When blood glucose levels drop, alpha cells in the pancreas release glucagon into the blood stream. Glucagon will induce muscle and liver cells to break down glycogen into glucose. Liver cells release that glucose back into the bloodstream, bringing blood glucose levels closer to the set point.

Regulation of Blood Glucose Levels by Insulin

Cells of the body require nutrients in order to function, and these nutrients are obtained through feeding. In order to manage nutrient intake, storing excess intake and utilizing reserves when necessary, the body uses hormones to moderate energy stores. Insulin is produced by the beta cells of the pancreas, which are stimulated to release insulin as blood glucose levels rise (for example, after a meal is consumed). Insulin lowers blood glucose levels by enhancing the rate of glucose uptake and utilization by target cells such as liver cells and skeletal muscle cells, which have the capacity to store carbohydrates. Specifically, it stimulates liver and skeletal muscle cells to convert glucose to glycogen, which is then stored by cells for later use. Insulin also increases glucose transport into certain cells. This results from an insulin-mediated increase in the number of glucose transporter proteins in cell membranes, which remove glucose from circulation by facilitated diffusion (Figure 2).

Figure 2. Regulation of blood glucose levels by insulin. When blood glucose levels increase, beta cells in the pancreas release insulin into the blood stream. Insulin will induce muscle and liver cells to increase their uptake of glucose from the bloodstream. Both cell types will use the excess glucose to make and store glycogen. This will quickly bring blood glucose levels closer to the set point.

As insulin binds to its target cell via insulin receptors and signal transduction, it triggers the cell to incorporate glucose transport proteins (GLUT-4) into its membrane. This allows glucose to enter the cell, where it can be used as an energy source. However, this does not occur in all cells: some cells, including those in the kidneys and brain, can access glucose without the use of insulin. Insulin also stimulates the conversion of glucose to fat in adipocytes and the synthesis of proteins. These actions mediated by insulin cause blood glucose concentrations to fall, called a hypoglycemic “low sugar” effect, which inhibits further insulin release from beta cells through a negative feedback loop.

Impaired insulin function can lead to a condition called diabetes mellitus, which is characterized by unusually high blood glucose levels (hyperglycemia). If left untreated, this can be dangerous and cause vision loss, strokes, and lethargy. This can be caused by low levels of insulin production by the beta cells of the pancreas (Type I diabetes), or by reduced sensitivity of tissue cells to insulin (Type II diabetes). In both cases, this prevents glucose from being absorbed by cells, causing high levels of blood glucose, or hyperglycemia (high sugar). High blood glucose levels make it difficult for the kidneys to recover all the glucose from nascent urine, resulting in glucose being lost in urine. High glucose levels also result in less water being reabsorbed by the kidneys, causing high amounts of urine to be produced; this may result in dehydration. Over time, high blood glucose levels can cause nerve damage to the eyes and peripheral body tissues, as well as damage to the kidneys and cardiovascular system. Oversecretion of insulin can cause hypoglycemia, low blood glucose levels. This causes insufficient glucose availability to cells, often leading to muscle weakness, and can sometimes cause unconsciousness or death if left untreated.