Insulin is a hormone. And like many hormones, insulin is a protein. Insulin is secreted by groups of cells within the pancreas called islet cells. The pancreas is an organ that sits behind the stomach and has many functions in addition to insulin production. The pancreas also produces digestive enzymes and other hormones. Carbohydrates (or sugars) are absorbed from the intestines into the bloodstream after a meal. Insulin is then secreted by the pancreas in response to this detected increase in blood sugar. Most cells of the body have insulin receptors that bind the insulin that is in the circulation. When a cell has insulin attached to its surface, the cell activates other receptors designed to absorb glucose (sugar) from the bloodstream into the inside of the cell.

Without insulin, you can eat lots of food and actually be in a state of starvation since many of our cells cannot access the calories contained in the glucose very well without the action of insulin. This is why people with type 1 diabetes who do not make insulin can become very ill without insulin shots. Insulin is a necessary hormone. Those who develop a deficiency of insulin must have it replaced via shots or pumps (type 1 diabetes).  

What is the role of pancreas?


Insulin Basics: How Insulin Helps Control Blood Glucose Levels

Insulin and glucagon are hormones secreted by islet cells within the pancreas. They are both secreted in response to blood sugar levels, but in opposite fashion!

Insulin is normally secreted by the beta cells (a type of islet cell) of the pancreas. The stimulus for insulin secretion is a HIGH blood glucose…it’s as simple as that! Although there is always a low level of insulin secreted by the pancreas, the amount secreted into the blood increases as the blood glucose rises. Similarly, as blood glucose falls, the amount of insulin secreted by the pancreatic islets goes down. 

Glucagon is secreted by the alpha cells of the pancreatic islets in much the same manner as insulin… except in the opposite direction. If the blood glucose is high, then no glucagon is secreted. 

When blood glucose goes low, however, (such as between meals, and during exercise) more and more glucagon is secreted. Like insulin, glucagon has an effect on many cells of the body, but most notably the liver.

The Role of Glucagon in Blood Glucose Control

The effect of glucagon is to make the liver release the glucose it has stored in its cells into the bloodstream, with the net effect of increasing blood glucose. Glucagon also induces the liver (and some other cells such as muscle) to make glucose out of building blocks obtained from other nutrients found in the body (e.g., protein).

Our bodies desire blood glucose to be maintained between 70 mg/dl and 110 mg/dl (mg/dl means milligrams of glucose in 100 milliliters of blood). Below 70 is termed “hypoglycemia.” Above 110 can be normal if you have eaten within 2 to 3 hours. That is why your doctor wants to measure your blood glucose while you are fasting…it should be between 70 and 110. Even after you have eaten, however, your glucose should be below 180. Above 180 is termed “hyperglycemia” (which translates to mean “too much glucose in the blood”). If your two blood sugar measurements are above 200 after drinking a sugar-water drink (glucose tolerance test), then you are diagnosed with diabetes.  

History of Insulin

The modern age has been full of amazing technological advances — high-speed travel, the Internet, etc. However, if you have type 1 diabetes, you are no doubt a big fan of one particular 20th century innovation: insulin therapy. Before there was insulin therapy, people whose bodies stopped producing the hormone didn’t hang around for long; there wasn’t much doctors could do for them.

In the 19th century, after researchers figured out that the body needs this critical hormone to burn glucose as energy, doctors tried different ways to restart production of insulin in people with type 1 diabetes. Some physicians even tried feeding fresh pancreas to patients. The experiment failed (and probably left more than a few patients begging for a palate-cleansing sorbet), as did the other attempts to replace missing insulin.

Finally, in 1922, a former divinity student named Dr. Frederick Banting determined how to extract insulin from a dog’s pancreas. Skeptical colleagues said the pancreas looked like “thick brown muck.” Banting injected the insulin into the keister of a 14-year-old boy named Leonard Thompson, whose body was so ravaged by diabetes that he weighed only 65 pounds. Little Leonard developed abscesses on his bottom and still felt lousy, though his blood sugar improved slightly. Encouraged, Banting refined the formula for insulin and tried again six weeks later. This time Leonard’s condition improved rapidly. His blood sugar dropped from 520 mg/dl to a more manageable 120 mg/dl. He gained weight, and his strength returned. (Poor Lenny — although his diabetes remained in control for years, he died of pneumonia when he was just 27.)

Banting and a colleague, Dr. John Macleod, won the Nobel Prize for their work. Commercial production of insulin for treating diabetes began soon after. For many years, drug companies derived the hormone using pancreases that came primarily from stockyards, taken from slaughtered cows and pigs, which didn’t need the organs anymore.

Animal insulin has saved millions of lives, but it has a problem: it causes allergic reactions in some users. In 1978, a fledgling biotechnology company named Genentech produced the first synthetically manufactured insulin that could be made in large amounts. Using bacteria or yeast as miniature “factories,” the gene for human insulin was inserted into bacterial DNA. The result was human insulin, called recombinant DNA insulin, which did not cause the problems that animal insulin sometimes did.

When it became widely available in the early 1980s, this new insulin changed the treatment of diabetes forever. Today, almost all people with diabetes who require insulin use a form of recombinant human insulin rather than animal insulin.

Types of Insulin

Today all over the world, biosynthetic human insulin is made by recombinant DNA technology, a scientific process that allows for the production of nearly unlimited quantities of human insulin. Because insulin needs vary from person to person, different types of human insulin are available.

These include:

  1. Regular or R: a short acting insulin that begins to work within 30-60 minutes, it’s  action peaks between 2 to 4 hours after it is injected and lasts 5 to 8 hours. It is injected 30 minutes before a meal with an aim to control the post-meal rise in blood glucose. In other words it is a “prandial or bolus”  insulin. As it’s action continues for 5-8 hours it would also help to cover a small mid-meal snack. This is the original bolus insulin and is still widely used despite availability of the newer rapid-acting analogs.

  2. NPH or N: an intermediate-acting insulin that begins it’s action in 2-4 hours after injection, the action peaks between 4 to 12 hours and lasts 12 to 20 (rarely 24) hours. This insulin has a cloudy appearance (all other insulins are clear and watery in appearance) and the vial / cartridge must be rotated between the palms 12-20 times before each use to ensure a uniform suspension. This is the original “basal insulin” (the insulin that regulates the amount of glucose that enters the blood from stores in the liver to maintain blood glucose over 70 mg% between meals, when there is no glucose coming from the gut). It is now largely replaced by the long-acting analogs for reasons mentioned below. 

  3. Lispro, Aspart, Glulisine: These are rapid acting insulins. Rapid-acting insulins (insulin analogs) are “designer insulins” in which some amino acids of the human regular insulin molecule  have been replaced / reversed with an aim to have a faster onset of action (15-35 minutes) and a higher peak level in blood thus controlling post-meal blood glucose more efficiently than regular insulin (R). The action of these insulins peaks between 1-2 hours and lasts 3-5 hours. As these insulins would not cover a mid-meal snack an additional injection may be needed for a snack or the child can opt for a low carbohydrate snack.

  4. Ultra-rapid acting Aspart and Lispro: These ultra-rapid acting variants of aspart and lispro have an even quicker onset of action (10-20 minutes) making them very useful in children and particularly in toddlers who would not like to wait long after injection to begin their meal.  Their peak action and duration of action however are similar to the rapid acting analogs. 

  5. Long acting analogs (Glargine, Levemir): These insulins were developed to replace NPH. They have been designed keeping in mind the shortcomings of NPH. Thus, glargine works 24 hours and can be injected once a day in 80% of patients. Both glargine and levemir are virtually peakless hence in comparison to NPH the risk of night-time hypoglycemia is reduced and there is less need for snacking in daytime and less risk of weight gain (these being significant disadvantages with NPH). Both glargine and levemir are more expensive than NPH and glargine does cause a slight stinging or burning sensation at injection site in some children.

  6. Ultra-long acting analogs (Degludec, Glargine-300):  these analogs work longer than the long acting ones and hence a single injection a day invariably suffices and further, it is not necessary to be very rigid about the timing of injection. Those who are not well controlled on once a day glargine or levemir can switch to degludec or to glargine-300.

Current Insulin Delivery Systems

  1. Insulin syringes are available with 40 or 100 subdivisions per ml. The 40 IU syringe has 40 subdivisions with each subdivision representing 1 unit while the 100 IU syringe has 50 subdivision with each subdivision representing 2 units. The 40 IU syringe has a red cap while the 100 IU syringe has an orange cap. Syringes are used for injecting insulin that is supplied in vials. On India insulin vials are available in 2 strengths: 40 IU per ml. and 100 IU per ml.

  2. Insulin pens look like a pen and are loaded with a 3 ml. cartridge containing insulin in a concentration of 100 IU per ml. or 300 IU per ml. Pens may be disposable (for one time use) or reusable (the cartridge is replaced when empty). Insulin pens deliver insulin in increments of 1 unit or in some instances 0.5 units.

  3. Insulin jet injectors look like a large pen. They send a fine spray of insulin through the skin at high pressure. These tend to be expensive.

  4. Insulin pumps are about the size of a pager. These are attached to the body through a narrow flexible tube with a needle just under the skin. A refillable cartridge holds insulin good for about 3 days. The needle and tubing need to be changed every 3 days and frequent glucose monitoring is necessary, but usually no more than if you take multi-injections a day to keep tight control.