Chapter 41: Insulin, Glucagon, and Oral Hypoglycemic Drugs

ORGANIZATION OF CLASS

A high level of glucose stimulates an increase in insulin release from β cells of the pancreas. Insulin then drives carbohydrate into cells. Patients who have high glucose levels in their blood are said to have diabetes mellitus.

Of course, you remember that diabetes mellitus is divided into two groups: type 1 (insulin dependent) and type 2 (insulin resistant). These distinctions are important for pharmacology because they make it easier to remember the mechanism of action of the drugs used to treat diabetes mellitus.

As an aside, there is another form of diabetes that students sometimes confuse with diabetes mellitus and that is diabetes insipidus. Diabetes insipidus is a disorder of water and sodium balance. Generally, if someone says diabetes, they mean the sugar-related (mellitus) disease and not diabetes insipidus.

But let’s return to the topic at hand.

This, of course, is somewhat simplified. An endocrinologist would cringe. Patients with type 1 diabetes are dependent on an exogenous (outside the body) source of insulin. This disorder generally appears in childhood; hence, the former term for it is juvenile diabetes. Type 2 diabetes has been called adult-onset. It appears to have a genetic basis, and patients are often obese. Patients with type 2 diabetes are treated with oral agents that lower blood glucose (hypoglycemics) and with insulin.

So, that said, we should organize our drugs into insulins and the oral hypoglycemic agents.

INSULINS

Insulin is a small protein that is synthesized and secreted by the β cells of the pancreas. Insulin for replacement therapy can be isolated from animal sources. Human insulin is made using recombinant DNA technology.

All peptides are degraded by enzymes in the gastrointestinal (GI) tract, so it is not possible to administer insulin by the oral route. Given intravenously, it has a half-life of less than 10 minutes (short). Therefore, it is administered subcutaneously.

I hope that this is intuitively obvious.

The onset and duration of action of the insulin preparations are controlled by the size and composition of the crystals in the particular insulin preparation.