**2. Historical perspective of insulin**

Although diabetes mellitus was always recognised as a distinct entity for more than 3000 years, its exact cause was not known until the twentieth century.

Till the early 1920s, many investigators were of the strong suspicion that diabetes was caused by a malfunction in the digestive system related to the pancreas gland. During that time the fatal disease was treated by a diet which was low in sugar and carbohydrates and high in protein and fat.

In those days, the patient usually died shortly after diagnosis, but the above diet allowed them to live for some years.

However, Best and Banting [1], **Figure 1**, two Canadians, provided a great relief to the world when they were able to isolate insulin from canines. They first produced diabetogenic symptoms in dogs and then with the help of insulin injections returned the dogs to normalcy. On the morning of November 14, 1921, they announced their discovery to the world. Then on January 23, 1922, they first injected Canadian 14-year-old Leonard Thompson with insulin and continued the treatment for diabetes mellitus.

Banting [2], **Figure 2**, by virtue of his tedious research, was able to create a pancreatic extract, which enabled him to gather thousands of islet cells. He then prepared extracts of insulin from these islets.

Initially, the insulin was tested on dogs, and it was able to regulate their blood glucose levels. Then in 1922 they tested it on Leonard Thompson, who became the first human being to be

given insulin. The first dose was a failure as it was not purified enough, but the second dose

Introductory Chapter: Historical Perspective and Brief Overview of Insulin

http://dx.doi.org/10.5772/intechopen.81183

3

**Figure 2.** Sir Frederick Grant Banting, KBE, MC, FRS, FRSC (November 14, 1891–February 21, 1941) (Source: [2]).

Development of insulin was done further by Banting along with laboratory director John MacLeod, and both of them were awarded the Nobel Prize in Physiology of Medicine in 1923.

The first person who promoted the benefits of a low-carbohydrate diet was Banting [3], **Figure 3**, originally referred to as the 'Banting diet'. After almost a period of 150 years post his publication of the renowned booklet 'Letter on Corpulence', addressed to the public (in the year 1863), the Banting diet has been backed up by several clinical trials as being safe and effective for weight loss, and it is now finally being acknowledged as a beneficial diet for people with diabetes.

It should be noted that Banting was not a scientist, but a highly skilful carpenter. While he was young, Banting became overweight, and he was told by a doctor to exercise more. But it did not help him. He tried a variety of weight loss options but failed in almost all of them. Then he met Harvey who told him to give up butter, bread, milk, beer, sugar and potatoes i.e. foods which contained sugar and starch. After 5 months, Banting returned to normal

Best [4], **Figure 4**, also helped Frederick Banting in discovering insulin in 1922 after he became Banting's assistant in the summer of 1921. After being awarded the Nobel Prize in 1923 with

which was purified by James B. Collip proved to be successful.

weight and he was more agile.

**Figure 1.** Charles Herbert Best, CC, CH, CBE, FRS, FRSC, FRCP (February 27, 1899–March 31, 1978) and Sir Frederick Grant Banting, KBE, MC, FRS, FRSC, (November 14, 1891–February 21, 1941) (Source: [1]).

Introductory Chapter: Historical Perspective and Brief Overview of Insulin http://dx.doi.org/10.5772/intechopen.81183 3

**2. Historical perspective of insulin**

protein and fat.

2 Ultimate Guide to Insulin

from these islets.

them to live for some years.

its exact cause was not known until the twentieth century.

and continued the treatment for diabetes mellitus.

Although diabetes mellitus was always recognised as a distinct entity for more than 3000 years,

Till the early 1920s, many investigators were of the strong suspicion that diabetes was caused by a malfunction in the digestive system related to the pancreas gland. During that time the fatal disease was treated by a diet which was low in sugar and carbohydrates and high in

In those days, the patient usually died shortly after diagnosis, but the above diet allowed

However, Best and Banting [1], **Figure 1**, two Canadians, provided a great relief to the world when they were able to isolate insulin from canines. They first produced diabetogenic symptoms in dogs and then with the help of insulin injections returned the dogs to normalcy. On the morning of November 14, 1921, they announced their discovery to the world. Then on January 23, 1922, they first injected Canadian 14-year-old Leonard Thompson with insulin

Banting [2], **Figure 2**, by virtue of his tedious research, was able to create a pancreatic extract, which enabled him to gather thousands of islet cells. He then prepared extracts of insulin

Initially, the insulin was tested on dogs, and it was able to regulate their blood glucose levels. Then in 1922 they tested it on Leonard Thompson, who became the first human being to be

**Figure 1.** Charles Herbert Best, CC, CH, CBE, FRS, FRSC, FRCP (February 27, 1899–March 31, 1978) and Sir Frederick

Grant Banting, KBE, MC, FRS, FRSC, (November 14, 1891–February 21, 1941) (Source: [1]).

**Figure 2.** Sir Frederick Grant Banting, KBE, MC, FRS, FRSC (November 14, 1891–February 21, 1941) (Source: [2]).

given insulin. The first dose was a failure as it was not purified enough, but the second dose which was purified by James B. Collip proved to be successful.

Development of insulin was done further by Banting along with laboratory director John MacLeod, and both of them were awarded the Nobel Prize in Physiology of Medicine in 1923.

The first person who promoted the benefits of a low-carbohydrate diet was Banting [3], **Figure 3**, originally referred to as the 'Banting diet'. After almost a period of 150 years post his publication of the renowned booklet 'Letter on Corpulence', addressed to the public (in the year 1863), the Banting diet has been backed up by several clinical trials as being safe and effective for weight loss, and it is now finally being acknowledged as a beneficial diet for people with diabetes.

It should be noted that Banting was not a scientist, but a highly skilful carpenter. While he was young, Banting became overweight, and he was told by a doctor to exercise more. But it did not help him. He tried a variety of weight loss options but failed in almost all of them.

Then he met Harvey who told him to give up butter, bread, milk, beer, sugar and potatoes i.e. foods which contained sugar and starch. After 5 months, Banting returned to normal weight and he was more agile.

Best [4], **Figure 4**, also helped Frederick Banting in discovering insulin in 1922 after he became Banting's assistant in the summer of 1921. After being awarded the Nobel Prize in 1923 with

J.J.R. MacLeod, Banting shared the prize money with Best and the rest of his team that were responsible for insulin being developed. Best was instrumental in doing the chemical tests to

Introductory Chapter: Historical Perspective and Brief Overview of Insulin

http://dx.doi.org/10.5772/intechopen.81183

5

Thompson [5], **Figure 5**, was the first patient having diabetes to receive insulin injections on January 11, 1922. Almost facing death, Leonard survived for another 13 years. Leonard, who

He was severely diabetic and was coming in and out of a diabetic coma and was weighing only 65 pounds. It was Leonard's father who gave the consent that his son should be the first person to test insulin, which was never previously been tried on another human being.

Initially the impure form of insulin was unable to make any impact in Leonard's condition; however, a purer version of insulin made him survive and his parameters came back to

One of the most unique approaches to diabetes treatment was provided by Proctor [6], **Figure 6**, in the early 1900s, as he concentrated on patients taking their own responsibility. Joslin made his mother survive through diabetes for 10 years through a rigorous combination of exercise, meal planning and food management. He was the founder of Joslin Diabetes

The 'starvation diet' was first proposed by Allen [7], **Figure 7**, who proposed it before the

was diagnosed some years previously, was admitted in Toronto General Hospital.

measure blood glucose levels while working with the team.

discovery of insulin to increase the life span of diabetes patients.

normal.

Center.

**Figure 5.** Leonard Thompson (Source: [5]).

**Figure 3.** William Banting (c. December 1796–March 16, 1878) (Source: [3]).

**Figure 4.** Charles Herbert Best, CC, CH, CBE, FRS, FRSC, FRCP (February 27, 1899–March 31, 1978) (Source: [4]).

J.J.R. MacLeod, Banting shared the prize money with Best and the rest of his team that were responsible for insulin being developed. Best was instrumental in doing the chemical tests to measure blood glucose levels while working with the team.

Thompson [5], **Figure 5**, was the first patient having diabetes to receive insulin injections on January 11, 1922. Almost facing death, Leonard survived for another 13 years. Leonard, who was diagnosed some years previously, was admitted in Toronto General Hospital.

He was severely diabetic and was coming in and out of a diabetic coma and was weighing only 65 pounds. It was Leonard's father who gave the consent that his son should be the first person to test insulin, which was never previously been tried on another human being.

Initially the impure form of insulin was unable to make any impact in Leonard's condition; however, a purer version of insulin made him survive and his parameters came back to normal.

One of the most unique approaches to diabetes treatment was provided by Proctor [6], **Figure 6**, in the early 1900s, as he concentrated on patients taking their own responsibility.

Joslin made his mother survive through diabetes for 10 years through a rigorous combination of exercise, meal planning and food management. He was the founder of Joslin Diabetes Center.

The 'starvation diet' was first proposed by Allen [7], **Figure 7**, who proposed it before the discovery of insulin to increase the life span of diabetes patients.

**Figure 5.** Leonard Thompson (Source: [5]).

**Figure 3.** William Banting (c. December 1796–March 16, 1878) (Source: [3]).

4 Ultimate Guide to Insulin

**Figure 4.** Charles Herbert Best, CC, CH, CBE, FRS, FRSC, FRCP (February 27, 1899–March 31, 1978) (Source: [4]).

It was Allen, a physician, who first proposed that restriction in calorie intake and engaging oneself in regular exercise resulted in the prolongation of the life of insulin-producing beta cells.

Introductory Chapter: Historical Perspective and Brief Overview of Insulin

http://dx.doi.org/10.5772/intechopen.81183

7

Allen, who was born in Iowa, studied medicine at the University of California. He attended Harvard Medical School between 1909 and 1912, and thanks to his father's financing, he also

Insulin receptors were thoroughly studied mostly by Kahn [8], **Figure 8**. He spent most of his

Kahn currently works as the Chief Academic Officer and Head of Joslin's Section on Integrative

He thoroughly investigated how cells are affected by insulin and the reason behind why only a particular group of cells develops insulin resistance, which is one of the main causes of type

career investigating the role of insulin sensitivity in obesity and diabetes.

**3. Early research**

2 diabetes.

published *Studies on Diabetes and Glycosuria* in 1913.

Physiology and Metabolism at the Joslin Diabetes Center.

**Figure 8.** Carl Ronald Kahn (born January 14, 1944) (Source: [8]).

**Figure 6.** Elliott Proctor Joslin, MD (June 6, 1869–January 28, 1962) (Source: [6]).

**Figure 7.** Frederick Madison Allen (1879–1964) (Source: [7]).

It was Allen, a physician, who first proposed that restriction in calorie intake and engaging oneself in regular exercise resulted in the prolongation of the life of insulin-producing beta cells.
