Extraction of insulin from islet of Langerhans

The term of “diabetes” was coined by the Greek Aretaeus in the second century AD. In 1776, the Liverpool physician, natural philosopher and experimental physiologist Matthew Dobson (1732 or 1735–1784) discovered that urine of diabetic patients is sweet because of excess in sugar.

In 1869, Paul Langerhans discovered with his doctoral thesis the existence of clusters of cells in the pancreas, despite their function was unknown. Islets of Langerhans are islands of endocrine cells scattered throughout the pancreas. However, the link between diabetes and the pancreas was not discovered until 1889 by Minkowski and von Mering.

In 1909, the Belgian Jean de Meyer coined the term “insuline” to refer to the “internal secretions” of the pancreas, from the Latin word for “island”. In 1910 and later in 1916, in London, Sir Edward Albert Sharpey-Schafer described in depth that the pancreatic islands are able to secrete a substance capable of controlling glucose metabolism.

There were many attempts to isolate the “internal secretions” of the pancreas during the first two decades of the twentieth century.

It was not until October 1920 that Fredrick G. Banting, a young orthopedic surgeon, got inspired while reading an article to prepare a lecture about the pancreatic islets of Langerhans and diabetes. He believed that earlier failures were attributable to the destructive action of trypsin.

Since November 1920, Banting began working in a laboratory led by John James Richard MacLeod. Banting's goal was to isolate the hormone secreted by the pancreatic islands.

He hypothesized that ligation of the pancreatic ducts before the extraction of the organ would destroy the acinar tissue, the enzyme-secreting compartment of the pancreas, while the islets of Langerhans would remain intact and able to produce the internal secretion regulating sugar metabolism.

In 1921 the Canadian scientists Banting, Charles H. Best, J. J. R. Macleod and James B. Collip discovered insulin, a peptide (small protein hormone) which lowers blood sugar. They extracted insulin from the islets of animal pancreases.

They closed the pancreatic ducts with a technique designed by Banting to get the degeneration of the pancreatic exocrine tissue and to obtain a pancreatic islet from the pure state. With this liquid extract, for the first time, in the history of medicine, Banting and Best found the way to control glucose in a diabetic animal.

Their experiments produced an extract of pancreas that reduced the hyperglycemia and glycosuria in dogs made diabetic by the removal of their pancreases. They next developed a procedure for extraction from the entire pancreas without the need for duct ligation.

The discovery of insulin, and the demonstration that it can lower blood glucose in dogs, by Frederick Banting and Charles Best in 1921, and its subsequent development for clinical use, in collaboration with John Macleod and James Collip, led to the award of the Nobel Prize in Physiology or Medicine to Banting and Macleod in 1923.
Extraction of insulin from islet of Langerhans

Ancient history of diabetes

Ebers Papyrus, which was written around 1500 BC, excavated in 1862 AD from an ancient grave in Thebes, Egypt, and published by Egyptologist Georg Ebers in 1874, describes, among various other ailments and their remedies, a condition of “too great emptying of the urine” – perhaps, the reference to diabetes mellitus. For the treatment of this condition, ancient Egyptian physicians were advocating the use of wheat grains, fruit, and sweet beer.

The condition was first termed ‘diabetes’ by Apollonius Memphites. Apollonius Memphites, an Egyptian physician at around 230 BC had used the prefix ‘diabetes’ for the first time to denote an excessive passage of urine and ascribed its aetiology to the kidney. In Greek, “diabetes” means “siphon.”

Diabetes, a Greek word was the term used to denote ‘run through or siphon’ in the description of incessant urination (Adams 1856), a word originally ascribed to Demetrios of Apamaia in the 200-250 BC.

The first attempt at describing the symptoms of diabetes was made by Aulus Cornelius Celsus (30 BC-50 AD) of Greece. Celsus had described an ailment which presented with excessive urination in frequency and volume, and painless emaciations.

By 500 A.D. two Indian physicians – Susruta and Charaka – had differentiated between the type 1 and type 2 forms of the disease. And they made observations of the sweetness of urine from observing ants congregating around the urine of patients. Sushruta uses the term “madhumeha” to refer to diabetes. “Madhu” means “honey” or “sweet,” and the whole term refers to the sweetness of diabetic urine.

They observed that thin individuals with diabetes developed diabetes at a younger age in contrast to heavier individuals with diabetes, who had a later onset and lived longer period of time after the diagnosis.

In the same year that Dumas gave glucose its name, the physician George Rees isolated sugar in excess from the blood of a patient with diabetes.
Ancient history of diabetes

History of diabetes

The first evidence of diabetes was recorded in the Egyptian Papyrus written in 1500 Bc and was discovered by Egyptologist Georg Ebers in Ad 1862 during the excavation of an ancient grave in Thebes.

It was within this document that a condition of "too great emptying of urine" was noted, perhaps a reference to the syndrome of diabetes.

Madhumeh (honey urine) was graphically described as a common disease by more than one Indian physician, notably Charaka (c AD 150).

Diabetes has also been recognized in China for thousands of years, where it is attributed to yin deficiency and treated with an integrated approach that involves more than lowering blood glucose.

Aretaeus of Cappadocia, a Greek physician who practiced in Rome and Alexandria in the second century AD, was the first to distinguish between what we now call diabetes mellitus and diabetes insipidus. In his work On the Causes and Indications of Acute and Chronic Diseases, he gave detailed account of diabetes mellitus and made several astute observations, noting, for example, that the onset of diabetes commonly follows acute illness, injury, or emotional stress.

Avicenna (A 980-1037), a famous Arab physician in Iran, clearly described diabetes mellitus and the “residue of honey” in the urine.

Willis in 1673 was the first doctor in modern Europe to describe, however briefly, that diabetic urine tasted ‘wonderfully sweet as if imbue with honey or sugar”.

Mathew Dobson

In 1774, Mathew Dobson, a physical practicing in Liverpool, discovered that the blood as well as the urine in diabetes, contains sugar, and from this observation he justly confirmed that the saccharine matter found in the urine is not formed in but only excreted by the kidneys.

William Prout (1785–1850) was the first to describe diabetic coma and Wilhelm Petters in 1857 demonstrated the presence of acetone in the urine of patients with diabetes. Adolf Kussmaul (1822–1902) proposed that acetonemia was the cause of diabetic coma.

Dr. Frederick Banting and his team used insulin to successfully treat a diabetic patient in 1922.
History of diabetes

History of Metformin

Metformin is the first-line pharmacologic treatment for patients with T2DM particularly in people who are overweight.

Its history can be traced from the use of Galega officinalis in medieval Europe as a treatment for symptoms of diabetes. In 1929, Slotta and Tschesche discovered the sugar-lowering action of metformin.

By 1950 a Philippine physician Eusebio Garcia used metformin to treat influenza and discovered that it also lowered the blood sugar. In 1957 Jean Sterne, a physician at the Hospital Laennec and Aron Laboratories in Paris, coins the name Glucophage. He noted the report form Garcia and investigated it clinically for the treatment of diabetes. He published clinical trial of diabetes was then completed and the UK introduced it in 1958 and Canada 1972.

Metformin is somewhat similar in structure to the drug “phenformin” which in 1977 was removed from the US market because of an increased risk of lactic acidosis.

A steady stream of in vivo studies can be seen in the early 1960s, hen USSR and various other European countries started when FDA approved metformin for the treatment of T2DM. It is currently being marketed by Bristol-Myers under the name of Glucophage.
History of Metformin

History of sulfonamide

Soon after the introduction of sulfonamide into clinical practice it was discovered that its antibacterial activity was antagonized by pus, as well as by tissue or yeast extracts. The revelation that sulfonamide was a systematically active antibacterial agent caught the attention of several companies. The first analogue was marketed in 1937 by Schering-Kahlbaum of Berlin, namely sulfacetamide.

A variety of antagonists of vitamins, hormones and cell metabolites had been synthesized after Donald Woods of Oxford University discovered in 1940 that sulfonamides exerted their antibacterial action by antagonizing the role of 4-aminobenzoic acid, a growth factor and essential for the survival parasites, be they bacteria, protozoa or viruses. Such antagonists were described as antimetabolites.

During World War II sulfonamides were used as wound dressings by the armed involved in the conflict. It has been estimated that more than 5000 sulfonamide does were prepared in the 1930s and 1940s.

In 1942, Marcel Janbon and co-workers discovered that sulfonylureas (sulfonamide derivatives) induced hypoglycemia in animals. These discoveries lead to antidiabetic drugs. These drugs use to manage Type 2 diabetes mellitus by increasing insulin release from the beta cells in the pancreas.
History of sulfonamide 

Dr. von Mering (28 February 1849, in Cologne – 5 January 1908)

Joseph Freiha von Mering was born in Halle an der Saale, Germany. He was well versed in pharmacology, laryngology and internal medicine and learned biochemistry from Hoppe-Seyler.

He studied in Bonn and in Greifswald, a small Prussian university town which had earlier joined the Hanseatic League. He graduated from the University of Strasbourg in 1873.
In 1877, Harmon Northrop Morse synthesized paracetamol at Johns Hopkins University by way of p-nitrophenol with tin in arctic acetic acid.

But it was not until 1887 that clinical pharmacologist Joseph von Mering attempted paracetamol on patients.

In 1893, von Mering issued a document informing on the clinical results of paracetamol with phenacetin, another aniline differential. Von Mering asserted that, unlike phenacetin, paracetamol had a small propensity to produce methemoglobinemia.

Paracetamol was then rejected in favor of phenacetin. It was not until the 1940s that paracetamol was reinvestigated after it was found present in proteins closed with phenacetin.

In 1889 together with Oskar Minkowski, von Mering discovered the direct connection between the pancreas and diabetes which led to the discovery of insulin. They found that the pancreas supplies a hormone essential to glucose metabolism. He reported in 1890 that the surgical removal of the pancreas from a healthy animal would cause diabetes.

Mering joined Naunyn’s Strasbourg Clinic of Internal Medicine, and in 1890 was appointed Associate Professor of Medicine at the outpatient department of Halle, Germany, and in 1900 as full professor of Internal Medicine in Medical Policlinic of Halle.

In 1903, Mering developed the chemicals structure of a drug that might produce sleep. Unable to synthesize the compound himself, he asked the great Emil Fisher at the University of Berlin for help and it was Fisher’s group that created the first of the barbiturates.
Dr. von Mering (28 February 1849, in Cologne – 5 January 1908)

The origin of diabetes name

The modern medical name for diabetes is diabetes mellitus. The first reference of diabetes was written in Ebers Papyrus by Egyptians physicians during 1500 BC.

In very ancient times the Greeks knew this disease. Aretaeus of Cappadocia in 2nd century declared, ‘Diabetes is a mysterious illness … where the flesh and limbs melt into urine’.

Doctors in ancient Greece and Rome named the disease. Fortunately, the way they tested for the condition – by tasting people’s urine. In this way, the Romans discovered that the urine of certain people was mellitus, the Latin word for sweet.

Diabetes means ‘passing through’ in Greek. The urine of people with diabetes contains sugar. It passes through the body quickly.

The Greek noticed that when people with sweet urine drank, the fluids came out in the urine almost as fast as they went in the month.

In 1776, Mathew Dobson from England determined that the sweet-tasting substance in the urine of diabetic individuals is sugar.
The origin of diabetes name

Diabetes in Ancient Times

Diabetes mellitus, usually referred to simply as “diabetes” had been known to mankind since ancient times.

Diabetes means “flowing though” and mellitus has it origin in the Latin word means “sweet as honey”.

In the past, diabetes was diagnose by tasting the urine. No effective treatment was available.

Ebers Papyrus, which was written around 1500 BC, describes diabetes mellitus treatment, ancient Egyptian physicians were practice diabetes disease management by manipulating the diet of his patients by giving them beer swill and cucumber.

Physicians in India at the same time observed that the urine from people with diabetes attracted ants and flies. They called the condition “honey urine”.

In 230 BC, Greek physicians considered diabetes a disease of the kidneys and recommended, among other ineffective treatments, such measures as bloodletting and dehydration.

Physicians in ancient Greece described in detail and gave the world its name. Aretaeus and Galen were two Greek physicians who listed symptoms of diabetes.

Aretaeus in 2nd century AD described a serious condition involving the ‘melting down of flesh and limbs into urine’. He observed that ‘life was short, unpleasant and painful, thirst unquenchable, drinking excessive and disproportionate to the large quantity of urine’.

The first human to be treated with insulin was a 14 year old boy, Leonard Thomson, in Canada in the year 1922.
Diabetes in Ancient Times