Maintenance of blood glucose level by the hormones insulin and glucagon

In this article, I briefly describe the maintenance of blood glucose levels by the hormones insulin and glucagon.

Hormones

Our endocrine system employs internal chemical messengers as hormones. These are produced by certain specific cell types. Hormones regulate the function of another tissue by binding to a distant cellular receptor. For binding with a receptor, hormones may act locally or may transported through the bloodstream.

Hormones regulate fuel metabolism by storing any excess fuel and appropriately mobilizing this stored fuel during times of need. The combined action of the hormones insulin, glucagon, epinephrine, and cortisol on metabolic processes, especially in liver, muscle, and adipose tissues, maintain a stable blood glucose level.

During higher blood glucose levels, insulin releases a signal to these tissues. As a result, cells take up extra glucose from the blood and convert it into the storage compounds glycogen and triacylglycerol. When the level of blood glucose slumps, then glucagon releases a signal to these tissues, which helps in the breakdown of glycogen. Thus, glucose is produced in the process of gluconeogenesis, and also oxidizing fats to minimize the use of glucose.

Insulin and glucagon are the most important hormonal regulators of anabolism and catabolism respectively. When the blood sugar level is lower than the standard level, a condition develops known as hypoglycemia. This is fought by the combined hormonal action of the hormones epinephrine, nor-epinephrine, cortisol, and growth hormone with glucagon, which opposes the action of insulin. Thus, the body is protected. During a low blood sugar level, the body first lowers the secretion of insulin and then releases glucagon.

When glucose homeostasis is not maintained in the body, it can lead to hypoglycemia or hyperglycemia, both of which have disastrous consequences.

Action of insulin

The utilization of dietary glucose in the body is promoted by the major anabolic hormone insulin. It suppresses glucose synthesis by the liver and encourages the storage of glucose as glycogen or fat. In the pancreas, clusters of specialized pancreatic cells, known as the islets of Langerhans, produce the peptide hormones insulin, glucagon, and somatostatin. There are three types of cells present in the islets, and each cell type produces a single hormone. The α cells of the islets produce glucagon, the β cells produce insulin, and the δ cells produce the hormone somatostatin. The level of glucose in the supplied blood to the pancreas regulates the insulin released by the pancreas. After the intake of a carbohydrate-rich meal, Insulin reduces blood glucose levels and re-establishes glucose homeostasis.

When the level of glucose in the blood rises, glucose is carried by GLUT2 transporters into the β cells of the pancreas. In the pancreas, it undergoes phosphorylation, and the enzyme responsible for the process is glucokinase. The enzyme converts glucose into glucose-6-phosphate, which enters glycolysis.

In the plasma membrane, ATP-gated K⁺ channels are closed due to the rise in ATP concentration. The rise in concentration of ATP is a result of the increased rate of glucose catabolism. Thus, reduced efflux of K⁺ depolarizes the membrane, which results in the opening of voltage-sensitive Ca²⁺ channels in the plasma membrane. The influx of Ca²⁺ pushes the release of insulin by the process of exocytosis.

Insulin controls the blood glucose level after a meal

Insulin is secreted, and the secretion is maintained till the blood glucose level falls. Within half an hour to 45 minutes after ingestion of a meal, the insulin level in the blood rises to its peak. It returns to a normal level nearly after 2 hours. Insulin is rapidly removed from the circulation and degraded by the liver.

The hormone insulin mainly targets skeletal muscle, cardiac muscle, adipose tissue, and liver. In the liver, insulin helps the channeling of glucose 6-phosphate into glycogen by activating the enzyme glycogen synthase and inactivating glycogen phosphorylase.

Insulin stimulates the storage of excess fuel as fat. Immediately after the intake of a meal filled with calories, glucose, fatty acids, and amino acids enter into the liver. High blood glucose concentration causes the release of insulin, which stimulates the tissues to uptake glucose.

Insulin converts excess blood glucose into glycogen and triacylglycerol

In the liver, insulin activates the oxidation of glucose 6-phosphate to pyruvate and pyruvate to acetyl-CoA, respectively. Fatty acid synthesis takes place from this acetyl-CoA. Fatty acids are then exported as the triacylglycerols of plasma lipoproteins (very low-density lipoproteins (VLDL)) to the adipose tissue (Figure 1).

In adipocytes, insulin stimulates the synthesis of triacylglycerol from fatty acids released from the VLDL triacylglycerols. These fatty acids are ultimately derived from the excess glucose taken up from the blood by the liver. So, Insulin converts the excess blood glucose into two storage forms, i.e., glycogen in the liver and muscle and triacylglycerols in adipose tissues.

Glucagon regulates blood glucose concentration

The hormone glucagon increases blood glucose concentration in various ways. Glucagon binds to the glucagon receptors of liver cells (hepatocytes). Then, it converts the glycogen polymer into glucose molecules and releases them into the bloodstream. This process is known as glycogenolysis. After that, glucagon spurs the liver and kidney to synthesize additional glucose through the process of gluconeogenesis (Figure 2).

Glucagon turns off glycolysis in the liver, causing glycolytic intermediates to enter into gluconeogenesis. Glucagon activates the enzyme glycogen phosphorylase and inactivates glycogen synthase, thus stimulating the breakdown of liver glycogen. The hormone blocks the conversion of phosphoenol pyruvate to pyruvate by inhibiting the glycolytic enzyme pyruvate kinase. It prevents the oxidation of pyruvate through the citric acid cycle. The resulting accumulation of phosphoenolpyruvate favors gluconeogenesis. Glucagon enables the liver to export glucose, restoring blood glucose to its normal level. It does this by stimulating glycogen breakdown, preventing glycolysis, and promoting gluconeogenesis in hepatocytes.

Lipolysis- The breakdown of lipids

Glucagon regulates the rate of glucose production through lipolysis. It is the process involving the breakdown of lipids. It also involves the hydrolysis of triglycerides into free fatty acids (Figure 2), followed by further degradation into acetyl units by beta-oxidation. The process produces Ketones, which are found in large quantities in ketosis. It is a metabolic state that happens when the liver converts fat into fatty acids and ketone bodies, which the body can use for energy.

G protein-coupled receptors triggered by glucagon activate adenylate cyclase. This results in increased production of cyclicAMP, which activates protein kinase A (PKA). PKA subsequently activates lipases found in adipose tissue. The activated lipase releases free fatty acids, which are exported to the liver and other tissues as fuel. In this way, it supplements glucose for the brain. The net effect of glucagon is therefore, to stimulate glucose synthesis. It also mobilizes fatty acids from adipose tissue to be used instead of glucose as fuel for tissues other than the brain.

Conclusion

Hormones are the internal chemical messengers that are employed by our endocrine system and are produced by certain specific cell types. The blood glucose level is maintained by the hormones insulin and glucagon. Insulin and glucagon are the most important hormonal regulators of anabolism and catabolism, respectively.

When the blood glucose is at an elevated level, Insulin releases a signal to the liver, muscle, and adipose tissues. As a result of which, cells take up extra glucose from the blood and convert it into the storage compounds glycogen and triacylglycerol. When the level of blood glucose suddenly decreases, glucagon releases a signal to these tissues. The signal helps in the breakdown of glycogen, thus producing glucose in the process of gluconeogenesis. This also oxidizes fats to minimize the use of glucose.

Glucagon stimulates glycogenolysis, where it binds to the glucagon receptors of liver cells (hepatocytes). Then, it converts the glycogen polymer into glucose molecules and releases them into the bloodstream. Glucagon enables the liver to export glucose, restoring blood glucose to its normal level.

The hormone glucagon also regulates the rate of glucose production through a process known as lipolysis. The process involves the breakdown of lipids.

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