Contributions of the american journal of physiology to the
discovery of insulin.
Youngren, Ira D. Goldfine Jack F.
Department of Medicine, Division of Diabetes and Endocrine
Research, Mount Zion Medical Center, University of California San
Francisco, San Francisco, California 94143-1616.
APStracts 4:0236E, 1997.
Since its inception in 1898 the American Journal of Physiology has
been a leader in diabetes research and has published many key
articles. The Journal first published studies of phlorizin- induced
diabetes in 1898, and after many other contributions went on to
publish the first reports of Banting, Best, Macleod, and Collip in
1922 concerning the isolation and purification of insulin (5-8,13).
This review will highlight some of these key contributions of the
Journal. Background- Diabetes mellitus is an ancient disease whose
symptoms were described over 3,500 years ago in the Papyrus Ebers. In
1872, this compendium of medical diseases was acquired in Luxor by
the Egyptologist George Ebers (28). The Roman physician, Celsus first
described diabetes mellitus in 10 AD as a disease of excess urination
and wasting (16). Diabetes is derived from a Greek word meaning going
through or siphon . Mellitus is the Latin word for honey or sweet.
Other Greco-Roman ancients mentioned the disease including Galen,
Aretaeus the Cappadician, and Demetius of Apamea (4,22,28). Diabetes
mellitus was also described by Indian physicians Charak and Sushrut
two millennia ago (22). Avicenna in Baghdad one millennia ago wrote
about diabetes mellitus and emphasized the sweetish taste of the
urine (22). For more than two thousand years diabetes mellitus was
believed to be a disease of the kidneys and bladder. This view was
supported and extended by the studies of Matthew Dobson, who in 1776
evaporated urine from a patient with diabetes mellitus and found that
the residue contained sugar (15).
Early search for the etiology and cure- The question arose as to the
origin of the glucose in the urine. In 1857 Claude Bernard described
glycogen as a product of glucose metabolism in liver and set forward
the concept that altered glucose metabolism is the cause of diabetes
(9). In 1869 Paul Langerhans discovered the Islets of Langerhans
(17,24). Others then observed pancreatic and Islet abnormalities in
necropsies of patients with diabetes mellitus. A major conceptual
breakthrough came with Minkowski whose studies clearly demonstrated
that removal of the pancreas lead to diabetes mellitus and lead to
concept that the internal secretions of the pancreas were involved in
the etiology of the disease (32). Whether these secretions regulated
the blood glucose or the kidney was uncertain. In the first year of
publication of the American Journal of Physiology, Lusk and
colleagues began to report a series of investigations demonstrating
that the agent, phlorizin, induced polyuria and glycosuria (27,31).
While it was subsequently discovered that the kidney was not the
primary pathological site in diabetes, nonetheless they made major
progress in understanding renal pathophysiology.
Received 23 October 1997; accepted in final form 24 October 1997
APS Manuscript Number E500-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 29 October 1997