The control of blood glucose
The control of blood glucose concentration is a critical aspect of homeostasis, which is the maintenance of a stable internal environment within restricted limits. Cells require a constant energy supply, with glucose being the principal respiratory substrate, especially for brain cells which can only respire glucose.
Importance of Maintaining Blood Glucose Levels
The normal blood glucose concentration in humans is typically around 90 mg per 100 cm³ of blood, or between 3.6 and 5.8 mmol/L. Deviations from this set point can lead to serious health problems:
Hyperglycemia (Too High Blood Glucose): If blood glucose concentration is too high, the water potential of the blood is reduced. This causes water molecules to diffuse out of cells into the blood by osmosis, which can lead to cells shriveling up and dying, and can also dehydrate the circulatory system. Prolonged hyperglycemia can damage blood vessels, increasing the risk of heart disease, stroke, kidney disease, blurred vision, and nerve problems.
Hypoglycemia (Too Low Blood Glucose): If blood glucose concentration is too low, cells are unable to carry out normal activities because there isn't enough glucose for respiration to provide energy. This can lead to unconsciousness, coma, and tissue damage, particularly affecting brain cells.
Key Organs, Cells, and Hormones
The control of blood glucose concentration is primarily regulated by the pancreas through the action of two antagonistic hormones: insulin and glucagon.
The pancreas contains clusters of cells called the islets of Langerhans, which act as both receptors and control centers. These islets contain two main types of cells:
Beta (β) cells: Secrete insulin.
Alpha (α) cells: Secrete glucagon.
1. Insulin's Action (When Blood Glucose is High)
When blood glucose concentration rises (e.g., after a meal containing carbohydrates), the β cells detect this increase and respond by secreting insulin, while the α cells stop secreting glucagon. Insulin then circulates in the blood and acts on target cells, primarily liver cells and muscle cells (and adipose tissue).
Insulin is a protein hormone, so it cannot directly cross cell membranes. Instead, it binds to specific receptors on the cell surface membranes of target cells. This binding triggers intracellular signaling, leading to several effects that lower blood glucose:
Increased glucose uptake: Insulin increases the permeability of muscle cell membranes to glucose, causing cells to take up more glucose from the blood. This involves increasing the number of GLUT4 channel proteins (glucose transporters) inserted into the cell membranes of skeletal and cardiac muscle cells from vesicles in the cytoplasm.
Glycogenesis: Insulin activates enzymes (like glycogen synthase) in muscle and liver cells that convert glucose into glycogen for storage. Glycogen is a large, insoluble polysaccharide easily converted back to glucose.
Increased glucose respiration: Insulin also increases the rate of glucose respiration, especially in muscle cells.
Fat deposition: Promotes the conversion of glucose to fatty acids and fats in liver cells, and their deposition in adipose tissue.
2. Glucagon's Action (When Blood Glucose is Low)
When blood glucose concentration falls too low, the α cells secrete glucagon and the β cells stop secreting insulin. Glucagon binds to specific receptors on the cell surface membranes of liver cells (muscle cells do not have glucagon receptors). This binding initiates a second messenger cascade within the liver cells, leading to increased blood glucose levels.
The key effects of glucagon are:
Glycogenolysis: It activates enzymes (e.g., glycogen phosphorylase) that break down glycogen into glucose in liver cells.
Gluconeogenesis: It activates enzymes involved in the formation of glucose from non-carbohydrate sources, such as glycerol (from lipids) and amino acids (from proteins).
Decreased glucose respiration: Glucagon decreases the rate of glucose respiration in cells.
3. Adrenaline's Role
Adrenaline (secreted from the adrenal glands during stress, exercise, or low blood glucose) also increases blood glucose concentration. It binds to different receptors on liver cell membranes but activates the same enzyme cascade as glucagon, leading to glycogenolysis. Adrenaline also stimulates glycogen breakdown in muscles, with the glucose remaining in muscle cells for respiration.
4. Second Messenger Model (Cell Signaling)
The action of peptide hormones like glucagon and adrenaline on liver cells illustrates a common cell signaling mechanism involving a second messenger.
Hormone-receptor interaction: The hormone (first messenger) binds to a specific receptor protein on the outer surface of the target cell's membrane. This binding causes a conformational change in the receptor.
Activation of G-protein and Adenylate Cyclase: The activated receptor stimulates a G-protein, which in turn activates the enzyme adenylate cyclase, an enzyme located in the cell membrane.
Formation of Cyclic AMP (cAMP): Adenylate cyclase catalyzes the conversion of ATP into cyclic AMP (cAMP), which acts as the second messenger inside the cell.
Enzyme cascade and amplification: cAMP then binds to and activates an enzyme called protein kinase A. This initiates a cascade of reactions where activated protein kinase A activates other enzymes (like phosphorylase kinase), which then activate glycogen phosphorylase. This cascade significantly amplifies the original signal, meaning a single hormone molecule can lead to the production of a very large number of glucose molecules.
Negative Feedback Control
The entire system of blood glucose regulation operates as a negative feedback loop. This means that any deviation from the normal blood glucose level triggers a response that counteracts the change, bringing the level back to its optimal range. The body has separate negative feedback mechanisms to actively increase or decrease blood glucose, providing a greater degree of control.
Connection to Diabetes Mellitus
Disruptions in blood glucose control lead to diabetes mellitus.
Type I diabetes results from the immune system attacking the β cells in the islets of Langerhans, preventing insulin production. It is treated with insulin therapy.
Type II diabetes (often linked to obesity, lack of exercise, age, and poor diet) occurs when β cells don't produce enough insulin, or target cells don't respond properly to insulin (due to faulty insulin receptors). It can often be managed with diet, exercise, and medication; insulin injections may eventually be needed.
When blood glucose levels are too high in diabetic individuals, the kidneys cannot reabsorb all the glucose from the filtrate, leading to glucose being excreted in the urine. This forms the basis for urine tests and biosensors used to monitor glucose levels.
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