Blood Glucose, Insulin and Diabetes

A Canadian story

In the summer of 1921, in a lab at the University of Toronto, the young surgeon Frederick Banting and the student Charles Best set out to isolate the mysterious substance made by the pancreas that seemed to control blood sugar. With help from J. J. R. Macleod, who ran the lab, and the biochemist James Collip, who purified their extract, they succeeded. In January 1922, a 14-year-old boy named Leonard Thompson, who was very ill with diabetes at Toronto General Hospital, became the first person to be treated with insulin. Before insulin, type 1 diabetes was nearly always fatal. Today, millions of people around the world live full lives with it.

Banting and Macleod received the 1923 Nobel Prize in Physiology or Medicine. Banting shared his prize money with Best, and Macleod shared his with Collip.

In this lesson you will learn how insulin and its partner hormone glucagon control blood glucose, what goes wrong in diabetes, and how it is treated today.

Why control blood glucose?

Glucose is the main fuel for cellular respiration (see Metabolic Processes). Your brain depends almost entirely on it. If blood glucose falls too low (hypoglycemia, below about 4 mmol/L), you can feel shaky, sweaty and confused, and in severe cases lose consciousness. If it stays too high (hyperglycemia) for months or years, it damages blood vessels and nerves.

In a healthy person, fasting blood glucose stays at about 4 to 6 mmol/L, rising to perhaps 7 or 8 after a meal and falling back within about 2 hours. The control centre is the pancreas. Most of the pancreas makes digestive enzymes (an exocrine job), but scattered through it are about a million tiny clusters of endocrine cells: the islets of Langerhans.

Insulin: the storage hormone

After a meal, glucose is absorbed from the small intestine and blood glucose rises. Beta cells in the islets detect this and release insulin. Insulin binds to receptors on target cells and:

• causes muscle and fat cells to move GLUT4 glucose transporters into their membranes, so glucose enters by facilitated diffusion (you met carrier proteins in Biochemistry);
• stimulates the liver and muscles to convert glucose into glycogen (glycogenesis);
• promotes fat storage and protein synthesis;
• signals the liver to stop releasing glucose.

Blood glucose falls back toward the set point, and insulin release decreases.

Glucagon: the release hormone

Between meals, overnight, or during exercise, blood glucose begins to fall. Alpha cells release glucagon, which acts mainly on the liver:

• glycogenolysis: breaking glycogen into glucose and releasing it into the blood;
• gluconeogenesis: making new glucose from amino acids and glycerol.

Blood glucose rises back to the set point. (Muscle glycogen is used by the muscle itself; only the liver releases glucose into the blood.) Epinephrine and cortisol also raise blood glucose, during stress, as you will see in the next lesson.

Symptoms, diagnosis and complications

Classic symptoms of high blood glucose are frequent urination, extreme thirst, fatigue, blurred vision and, in type 1, unexplained weight loss. Diabetes Canada uses these diagnostic values (only a doctor can diagnose, usually after repeating a test):

• fasting blood glucose of 7.0 mmol/L or higher, or
• A1C of 6.5% or higher, or
• blood glucose of 11.1 mmol/L or higher 2 hours after drinking 75 g of glucose (an oral glucose tolerance test, OGTT).

Over years, poorly controlled diabetes can damage the kidneys (it is a leading cause of kidney failure), the eyes (retinopathy), nerves (especially in the feet) and the heart and blood vessels. Good control greatly lowers these risks.

In type 1 diabetes, a lack of insulin can lead to diabetic ketoacidosis (DKA): cells can't take in glucose, so the body burns fat, producing acidic ketones. You saw this as a cause of metabolic acidosis in the acid–base lesson. DKA is a medical emergency.

Technologies for diabetes

• Human insulin made by bacteria and yeast. Early insulin came from cattle and pigs. Since the 1980s, recombinant DNA technology (see Molecular Genetics) has produced human insulin in genetically modified microorganisms. Modified "insulin analogues" act faster or longer.
• Glucose meters and continuous glucose monitors (CGMs). A CGM uses a tiny sensor under the skin to read glucose every few minutes and send it to a phone.
• Insulin pumps deliver insulin through a small tube under the skin. Some systems link a pump and a CGM with software that adjusts insulin automatically (sometimes called an "artificial pancreas"), a technological feedback loop.
• Islet transplantation. In 2000, a team led by Dr. James Shapiro at the University of Alberta reported the Edmonton Protocol, a method of transplanting donor islets into people with hard-to-control type 1 diabetes. Recipients need immunosuppressant drugs, so it is used for only a small number of patients.

For type 2 diabetes, regular physical activity and balanced eating help prevent it or delay it, and medications such as metformin reduce the liver's glucose output and improve insulin sensitivity.