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Hormonal regulation of blood glucose level and Diabetes mellitus

Throughout the day, the body constantly regulates glucose levels with its mechanisms.

Hormonal regulation of blood glucose level

Throughout the day, the body constantly regulates glucose levels with its mechanisms. To supply the cells of the body with the necessary energy, the BG level should range from 60 to 140 mg/dL. Even though neurons do not require insulin to transport glucose into them, there must still be adequate levels of glucose available to them. Hypoglycemia, or too little glucose in the blood, starves cells, while hyperglycemia, or too much glucose, paralyzes them. The body functions at its best when blood sugar levels are within the normal range or euglycemia. To maintain normal blood glucose levels, pancreatic, intestinal, brain, and even adrenal hormones need to be a delicate balance.

Hormones of pancreas

A negative feedback loop maintained by the pancreas regulates blood glucose largely through its endocrine hormones. Blood sugar is regulated by the hormones insulin, glucagon, somatostatin, and amylin. A decrease in BG levels is caused by insulin (from beta cells in the pancreas), while an increase is caused by glucagon (from alpha cells in the pancreas). It balances insulin and glucagon in the pancreas by forming somatostatin in the delta cells. By alternating between hormones, the pancreas can turn each opposing hormone on or off. Amylin is made in a 1:100 ratio with insulin, and is a hormone that increases satiety from meals, thereby preventing overeating. In addition, it delays the emptying of stomach contents, preventing blood sugar levels from rising rapidly. The pancreas turns on insulin production and shuts down glucagon production after a meal containing carbohydrates is eaten and digested. The glucose from the bloodstream will enter the liver cells if insulin and glucose are available, and several enzymes will convert the glucose into chains of glycogen.

When the liver is in a "fed" or postprandial state, it absorbs more glucose from the blood. Insulin secretion and glycogen synthesis drop immediately after digestion, and blood sugar levels fall. To transport glucose to the cells of the body, glycogen is broken down by the liver and converted into glucose. In a healthy liver, glycogen stores occupy up to 10% of its volume. Approximately 1% of glycogen is stored in muscle cells. For energy, glycogen is converted back into glucose by the liver and the liver regulates the amount of glucose in the bloodstream between meals. Keeping optimal levels of blood glucose requires your liver to know how much glucose to store, keep, or break down and release. The goal of externally controlled glucose levels is to mimic this information. To mimic this normal cycle, clinicians use base-bolus dosing. Despite the body's requirement for circulating glucose (60–100 mg/dl) in order to be healthy, high blood glucose levels are detrimental and toxic.
  • Acutely - Hyperglycemia >300 mg/dl results in dehydration due to polyuria. Hypoglycemia (greater than 500 mg/dl) can cause confusion, cerebral edema, comas, and death.
  • Chronically - An average blood sugar level of 120 to 130 mg/dl damages body tissues and increases a person's susceptibility to infection.
When glucose reaches the bloodstream, it becomes syrupy, intoxicating cells and stealing oxygen. While the body needs 60–100 mg/dl of circulating glucose to function properly, chronically elevated concentrations lead to health issues and are toxic. Glucose concentration in the blood is a function of both the rate at which glucose enters the circulation and the rate at which it leaves the circulation. Glucagon and insulin are pancreatic hormones that deliver signals to the body's different parts. As blood glucose levels fall, glucose is released into the bloodstream by the liver. The liver and muscles are signaled to rid the blood of glucose during times of high blood glucose concentration.

Role of insulin

Regulatory carbohydrate metabolism in the body is controlled by insulin, a peptide hormone made by beta cells of the pancreas. Once a meal is consumed, insulin will be released into the body. Insulin stimulates insulin-sensitive cells such as liver cells and fat cells to take up glucose for metabolization. Increased levels of blood glucose stimulate insulin production and release from beta cells. In addition to its anabolic effects, insulin has growth-promoting properties.

Role of glucagon

The pancreas produces the peptide hormone glucagon, which raises glucose levels in the body. The hormonal effect is the opposite of that of insulin. Glucagon releases glucose into the bloodstream by stimulating glycolysis and glycogen breakdown in the liver. Therefore, glucagon has catabolic properties, breaking down cells as opposed to insulin's anabolic properties. Low glucose levels cause the pancreas to release glucagon. By producing glucose in the bloodstream, glucose is converted from stored glycogen. Elevated blood sugar increases insulin production. When glucose is available in the bloodstream, muscles and other insulin-dependent tissues use it. Blood glucose levels are stabilized by glucagon and insulin in a negative feedback system.

Insulin injections can correct severe hypoglycemia due to their powerful ability to regulate blood sugar levels. When glucose is administered orally or parenterally, blood glucose levels rise quickly, but injections of exogenous glucagon do not raise blood glucose levels. It takes approximately 10 to 20 minutes for exogenous glucagon to reach the liver, where it triggers the breakdown of stored carbohydrates. Chronic hyperglycemia is a symptom of type 2 diabetes caused by excessive glucagon secretion. Somatostatin, produced by the delta cells of the pancreas, maintains the balance between these two opposing hormones, glucagon and insulin. A graphic showing how glucose is metabolized after eating.



Role of amylin

Amylin is secreted into the body in a 1:100 ratio along with insulin by the beta cells of the pancreas. Amylin inhibits the secretion of glucagon, thus lowering blood glucose levels. In addition, it lowers BG spikes after meals as well as increases brain satiety (satisfaction) in order to encourage feeling full after a meal. The brain-meal connection is regulated by this hormone. Amylin and insulin are not produced by people with type 1 diabetes. The intestinal incretin hormones that determine blood glucose and satiety are often disrupted in people with type 2 diabetes, resulting in their feeling of hunger all the time. Various pharmaceutical companies produce Amylin analogs that are available for the treatment of Amylin disorders.

Role of incretins

Food intake stimulates the secretion of incretins, glucagon-like peptides (hormones) in the small intestine that are secreted into the bloodstream. Blood glucose levels rise even before incretins get to work after a meal. In addition, they decrease gastric emptying, which may also lead to a decrease in food intake because they increase satiety. Many individuals with type 2 diabetes report feeling constantly hungry as a result of low incretin levels. Incretin mimetics have become a new class of medications to help balance blood sugar levels in people with diabetes after research showed that intestinal hormones are also involved in controlling sugar levels. GLP-1, or gastric inhibitory polypeptide, is one type of incretin hormone; GIP is another. The enzyme DDP-4, (dipeptidyl peptidase-4), naturally breaks down each peptide. Glucagon-like peptide (GLP-1) Byetta (exenatide) is an injectable glucose-lowering drug that mimics the effects of naturally occurring incretins. Exenatide reduces blood glucose levels by mimicking incretins. A wide variety of GLP-1 agents are currently available, including long- and short-acting ones.

Incretins perform the following functions:
  • Stimulate the secretion of insulin.
  • Suppress the production of glucagon.
  • Reduce gastric emptying to prevent blood sugar spikes.
  • After you finish eating, increase your satiety level to let your brain know you've had enough.
DPP-4 enzymes, in the bloodstream and on the surface of endothelial cells, are able to deactivate incretins quickly. Therefore, they have only a few minutes' effects in lowering blood glucose levels. A new class of drugs, called DPP4 inhibitors, blocks the action of this enzyme, allowing incretins to suppress blood sugar levels longer. Dipeptidyl peptidase-4 (DPP-4 inhibitors-please note the hyphen) is another class of medications that can be taken orally as well. An illustration showing the role of incretins and insulin.



Diabetes mellitus

Sugar (glucose) cannot be used by the body for energy when it has diabetes. This causes blood sugar levels to rise. The consequences of poorly managed diabetes can be severe, causing damage to your heart, kidneys, eyes, nerves, and a variety of other organs and tissues in your body.

Type 1 diabetes - A person with this type of disease attacks their own body. In the case of insulin-producing cells being destroyed, your pancreas is destroyed as well.

A person with type 1 diabetes is one out of every ten who has diabetes. A diagnosis is more likely to occur in a child or young adult (though it can happen at any age). Diabetes was formerly known as "juvenile" diabetes. Insulin injections are necessary for people with diabetes type 1. Insulin-dependent diabetes is also called this condition.

Type 2 diabetes - Insulin does not get absorbed by your cells normally, or not enough insulin is produced by your body. Diabetics who have this condition have the highest risk of complications. Type 2 affects about 95% of diabetics. Middle-aged and elderly people are most likely to have it. The term insulin-resistant diabetes is often used in conjunction with adult-onset diabetes. Some people refer to having a touch of sugar as "having a touch of sugar."

Prediabetes - This type of diabetes presents similar symptoms to type 2 diabetes. It's high enough that you are not diagnosed with Type 2 diabetes, but not high enough to raise your blood sugar over the normal levels.

Gestational diabetes - Pregnant women are at risk for developing this condition. Most women recover from gestational diabetes after delivering the baby. In later life, having gestational diabetes increases your risk of developing Type 2 diabetes.

Less common forms of diabetes include:
  • Monogenic diabetes syndrome - Only 4 percent of diabetes cases are caused by them, which are rare inherited forms of diabetes. The most common are neonatal diabetes and maturation-onset diabetes.
  • Cystic fibrosis-related diabetes - A specific form of diabetes that occurs in people with cystic fibrosis.
  • Drug or chemical induced diabetes - In some cases, these complications occur after organ transplantation, following HIV/AIDS treatment, or following glucocorticoid therapy.
An uncommon condition is known as diabetes insipidus results in excessive amounts of urine being produced by your kidneys.
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Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of Pharmaceutical Guidelines, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
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