HORMONES 301 



The name insulin comes from the Latin insula, meaning island, and 

 refers to the fact that the hormone is formed by small groups of special- 

 ized cells called the "islets of Langerhans." There are about 250,000 to 

 2,500,000 of these islets in man. Lack of insulin causes diabetes ■mellitus, 

 a fatal human disease characterized by excessive urinary excretion and by 

 the presence of large amounts of glucose in the urine. After this fact 

 was established around 1890, many efforts were made to prepare active 

 extracts from animal pancreas glands. They were without success be- 

 cause the hormone was destroyed by the proteolytic enzymes present. 

 The first really effective extracts were obtained in 1922 by Banting, Best, 

 Collip, and IMacLeod through the use of acidified alcohol, which inacti- 

 vated the enzymes. Because of the great demand for insulin for the 

 treatment of diabetes, commercial production was soon undertaken, and 

 many workers studied methods of purifying the crude extracts. Pure 

 crystalline insulin was finally isolated by Abel and co-workers in 1926. 



Chemical Nature. Insulin is a water- and alcohol-soluble protein, 

 having its isoelectric point at pH 5.3. The molecular weight has been 

 estimated at 36,000 to 48,000, but it is now known that these values repre- 

 sent aggregations of smaller units. The true molecular weight is gener- 

 ally considered to be 12,000.^ Insulin has a sulfur content of 3.1 per 

 cent, which is much higher than that of most other proteins. In spite 

 of much searching no organic prosthetic group or structure other than 

 the usual amino acids has ever been found as a component of insulin. 

 Crystalline insulin contains about 0.3 per cent of zinc, but this is of 

 doubtful significance as essentially zinc-free amorphous preparations 

 have equal biological activity. As a result of a brilliant series of re- 

 searches carried out during the last few years, chiefly by Sanger, the 

 structure of insulin is known in greater detail than is that of any other 

 protein (p. 132). 



Physiological Function. The appetite and thirst of the untreated 

 diabetic are enormous, but in spite of the great quantities of food and 

 drink consumed, the body weight becomes progressively less. Blood 

 glucose levels rise so much above the renal threshold that large amounts 

 are excreted in the urine (p. 327). Bodily glycogen stores are depleted. 

 Urinary excretion of nonprotein nitrogen compounds is increased as a 

 result of increased conversion of deaminated amino acids into carbohy- 

 drate. Excessive oxidation of fat occurs, and ketosis develops (p. 338). 

 These symptoms have usually been interpreted as being due to decreased 

 utilization of carbohydrates by the body, but some authorities believe 

 that the disease is more a result of increased formation of carbohydrates 

 (from fat and protein) than of decreased utilization. The over-produc- 



^ However, Fredericq and Neurath have recently obtained evidence that the actual 

 value may be only 6,000. Larger apparent molecular weights result from reversible 

 aggregation in solution, the extent of which depends on the pH, concentration*, tempera- 

 ture, and kind and amount of inorganic ions pi'esent. 



