- There are hormones that work against the action of insulin.
- The main counterregulatory hormones are glucagons, epinephrine, cortisol and growth hormone.
- Our body depends on the actions of a number of different hormones in controlling glucose use.
Diabetes is a medical condition wherein the blood sugar level becomes high. With type 1 diabetes, the body is unable to make insulin, while in type 2 diabetes, the body is unable to make or properly use insulin. Too much glucose in the blood can cause complications such as damage to the eyes, kidneys, and nerves. It can also cause stroke and heart disease.
The alpha cells of the pancreatic islets undergo processing to produce glucagon. Glucagon maintains the normal concentrations of blood glucose. It is said to work opposite to insulin. Glucagon is a peptide hormone with 29 amino acids. Its structure is related to the secretin family of peptide hormones. It is synthesized as proglucagon within the intestinal tract and then processed into a family of glucagon-like peptides. The effect of glucagon can be seen on the glucose level in the blood. By exerting control over two pivotal metabolic pathways in the liver, it causes the liver to release glucose to the rest of the body.
Functions of Glucagon
- When glucose levels are high in the blood, the liver takes up larger amounts of glucose. Under the influence of insulin, this extra glucose is stored as glycogen. Whenever the glucose level in the body reduces, glucagon is secreted and acts on the hepatocytes in the liver, and activates the enzymes that depolymerize glycogen. Thus, glycogen in the liver is stimulated to break down glucagon and glucose is released.
- The pathway by which non-hexose substrates are converted into glucose is known as gluconeogenesis. This is also another source of blood glucose. This job is done by glucagon by activating the gluconeogenic enzymes. Thus, glucagon activates hepatic gluconeogenesis, which carries out the process of gluconeogenesis by which glucose is obtained.
- In a minor way, triglyceride in the adipose tissues undergo lipolysis, and this process is enhanced by glucagon. Hence, glucose can be conserved by providing fatty acid fuel to most of the cells.
- To maintain blood glucose levels, glucagon reduces the consumption of glucose by the liver so that it can be released into the bloodstream.
Control of Glucagon Secretion
Glucagon is secreted in response to hypoglycemia or when the concentration of glucose is less in the blood since glucagon increases the level of glucose in the blood. Mostly after consumption of a meal rich in proteins, an increased level of amino acid triggers glucagon secretion. Glucagon fosters the conversion of excess amino acids to glucose by gluconeogenesis. The secretion of insulin is also stimulated when the levels of amino acid in the blood is high. In such situation, both the hormones insulin and glucagon would be active.
It is still not clear whether exercise stimulates glucagon secretion or the depletion of glucose due to exercise stimulates glucagon secretion.
According to the negative feedback mechanism, high levels of blood glucose and somatostatin inhibit glucagon secretion. Due to cancer of alpha cells, glucagon can be released in excess. The tumors lead to wasting syndrome, rashes, and skin lesions.
In type 1 and type 2 diabetes mellitus, insulin deficiency is the major cause, but the metabolic derangement seen in these conditions is due to aberrant secretion of glucagon. Although diseases associated with excessively high or low glucagon is rare, unusual cases of glucagon deficiency have been reported in babies. To restore the blood glucose level, which is lowered by insulin, glucagon can be administered by injection. It stimulates the increased release of glucose from glycogen stored in the liver. Once the person has recovered enough, it is important to have a carbohydrate meal once a day.
In people with type 1 diabetes, the insulin levels cannot change since they do not secrete insulin. Some people may even not be able to secrete glucagon. Such people are more prone to severe hypoglycemia. Fortunately, glucagon is available through Glucagon Emergency Kits, which can be purchased at pharmacies.
People with type 1 diabetes need to have a glucagon kit on hand to treat severe hypoglycemia. Glucagon helps restore the blood glucose level. When a person fails to consume food or drinks that contain carbohydrates and is in a state of hypoglycemia, a person, friend, or a family member can inject glucagon. The glucose level is restored within a period of 5-10 minutes.
In the kit are an inert solution, a vial containing crystallized glucagon, and a set of instructions that need to be read before using the kit. The solution is first injected into the vial and then shaken to dissolve the crystals of glucagon. It is then drawn into the syringe and injected into the muscles or under the skin. Stored glycogen can be converted into glucose by glucagon. The effectiveness of glucagon injection will vary depending on the amount of glucose reserve in the liver.
If a glucagon injection is given after a prolonged exercise, then it will be ineffective since the glycogen store would be depleted. It almost takes 24 hours for our body to maintain a normal blood glucose level by replenishing the glycogen store. Hence, after episodes of severe hypoglycemia, it is necessary to frequently monitor blood glucose levels as well as eating something.
Diabetes is of two types: type 1 and type 2 diabetes. Both types need medications to keep the blood glucose at normal levels.
Drugs for Type 1 Diabetes
1. Insulin - It is used for the treatment of both type 1 and type 2 diabetes and is one of the most common types of medication for diabetes. There are many types of insulin and the doctor may specifically prescribe a combination of the types of insulin to use.
- Rapid-acting Insulin - It includes insulin glulisine (Apidra), insulin lispro (Humalog), and insulin aspart (NovoLog, FlexPen).
- Short-acting Insulin - It includes insulin regular (Humulin R, Novolin R).
- Intermediate-acting Insulin - This type of insulin includes insulin isophane (Humulin N, Novolin N).
- Long-acting Insulin - It includes insulin degludec (Tresiba), insulin detemir (Levemir), and insulin glargine (Lantus, Toujeo).
2. Amylinomimetic Drugs - include Pramlintide (SymlinPen 120, SymlinPen 60). The drug is injected before meals. It delays the time taken by the stomach to empty itself. Moreover, it reduces the secretion of glucagon before meals, and thus, lowers the blood sugar level.
Medications for Type 2 Diabetes
Most type 2 diabetes medications are orally taken. A few of them are available in the form of injections.
2. Biguanides - These drugs lead to a decrease in the amount of sugar the liver makes and also decreases the amount of sugar the intestine absorbs, thereby making the body become more sensitive to insulin. It helps the muscles to absorb glucose. An example of metformin (Glucophage, Metformin Hydrochloride ER, Glumetza, Riomet, and Fortamet).
3. Dopamine Agonists - They include the drug bromocriptine (Parlodel) for the treatment of type 2 diabetes.
4. DPP-4 Inhibitors - These drugs help the pancreas synthesize more insulin. They include:
- alogliptin (Nesina)
- alogliptin-metformin (Kazano)
- linagliptin (Tradjenta)
- linagliptin-empagliflozin (Glyxambi)
5. Glucagon-like Peptides - They control the amount of glucagon the body uses. They include:
6. Meglitinides - They help the body release insulin.
7. Sodium-glucose Co-transporter-2 Inhibitors - They prevent the kidneys from retaining glucose and the body eliminates the glucose via the urine.
- dapagliflozin (Farxiga)
- dapagliflozin-metformin (Xigduo XR)
- canagliflozin (Invokana)
- canagliflozin-metformin (Invokamet)
8. Sulfonylureas - These drugs stimulate the pancreas and cause the beta cells to release more insulin. They are the oldest diabetes drugs still used nowadays.
- glimepiride (Amaryl)
- glimepiride-pioglitazone (Duetact)
- glimepiride-rosiglitazone (Avandaryl)
- gliclazide (Diamicron)
- glipizide (Glucotrol)
9. Thiazolidinediones - They reduce the glucose in the liver and also help the fats cells to use insulin.
- rosiglitazone (Avandia)
- rosiglitazone-metformin (Amaryl M)
- pioglitazone (Actos)
- pioglitazone-alogliptin (Oseni)
- pioglitazone-metformin (Actoplus Met, Actoplus Met XR)
How do hormones help diabetes patients?
The hormones that affect the blood sugar level need to be identified first.
- Insulin - The beta cells in the pancreas release insulin and they cause the body to use glucose for energy production. It also prevents the blood sugar level from getting too high or too low and maintains the normal blood sugar level. The beta cells are signaled to release insulin after eating a meal and the sugar from the blood is absorbed.
- Glucagon - The alpha cells in the islets of pancreas release glucagon and they control the production of glucose and ketone in the liver. Glucagon is essential for maintaining the blood sugar level in the body. It is released between meals and overnight. It stimulates the body to break down glycogen and starch reserves. Moreover, they help new units of ketone and glucose to form from other substances.
- Amylin - It is also released from the beta cells. It works by decreasing the levels of glucagon. It delays the emptying of the stomach by decreasing the production of glucose in the liver. The brain senses that the stomach is full and satisfied. Also, during meal time, amylin reduces the production of sugar, which then prevents the level of blood glucose becoming too high.
- Epinephrine - It is also known as adrenaline. Adrenal glands and nerve endings release epinephrine. They stimulate the liver to produce sugar and promote the breakdown as well as the release of fat nutrients. After reaching the liver, these nutrients are converted into ketone and sugar.
- Cortisol - It is a type of steroid hormone and is secreted by the adrenal gland. The muscles and fat cells become resistant to insulin action due to cortisol. Also, the production of glucose from the liver is enhanced due to cortisol. When the body is under stress, cortisol levels increase to a point where the body becomes resistant to insulin. People with type 1 diabetes need extra insulin.
- Growth Hormones - These hormones are released by the pituitary gland and their Their function is similar to cortisol. They counterbalance the effect of insulin. However, when the level of growth hormones become too high, the body becomes resistant to insulin.
Insulin treatment can cause low blood sugar, weight gain, and discomfort at the site of injection. The tablets used to treat diabetes can have different side effects such as diarrhea, nausea, weight gain, and low blood sugar levels. Some may even experience sexual dysfunction. Glucagon injections may cause side effects such as nausea, vomiting, and low blood sugar. Some individuals have even reported about allergy symptoms such as skin rashes and breathing problems.
Preliminary studies have revealed that giving an extra dose of naturally occurring hormones to type 2 diabetes patients may help fight the disease by correcting the imbalance. People with type 2 diabetes are not able to produce or synthesize enough amount of insulin that is required to absorb glucose in the cells to meet the energy level needed by the body. Modification in the diet, exercise, medications to lower blood glucose levels, and supplementation of insulin may be needed. If it is left untreated, complications can include kidney damage, loss of limbs, and blindness.
However, a certain study has published that a glucagon-like peptide can eventually become an alternative treatment for diabetes. This hormone is found in lower concentrations in people with type 1 diabetes and is associated with insulin production.
In a Danish research, 20 patients were given either intravenous injection of the hormone or saline placebo for six weeks. It was noted that those who received GLP-1 in several major areas showed improvement and reported without any side effects. The improvements were:
- Fasting and decreased eight-hour average blood glucose levels
- Loss of about 4 lbs in body weight
- Reduced appetite
- Sensitivity to insulin and improvement in cell function
This study proves that a GLP-1 based treatment is more likely to be effective in the long run. Thus, eventually along with the correction of the metabolic disturbance of the disease, it would be possible to restore the underlying cells, whose function is defective. About 10 percent of adults over 60 years old are affected with type 2 diabetes. The disease has also emerged in some children and teenagers as well.