We would like to develop this list to include seminal papers which have changed the way we view pancreatic physiology and disease. To insure perspective and the test of time it will be limited to material over 25 years old. Please forward your suggestions or willingness to write a commentary on a paper to pancreapedia@umich.edu. Commentaries can be anywhere from a paragraph to two pages long. The initial list represents the views of the Editors and focuses on normal function and pathology.
18th Century
Vater, Abraham. Dissertatio anatomica qua novum bilis diverticulum circa orificium ductus cholodochi ut et valvulosam colli vesicae felleae constructionem ... 1720; Wittenbergae, Lit. Gerdesianus, 4to. (Wellcome Inst Hist Med A.I.f(20) 13298
The Wittenberg physician, in the academic hierarchy of the 18th century promoted from Professor of Anatomy, to Professor of Pathology, then to Professor of Therapy, was the first to describe the existence and function of the ampulla (papilla) at which the common bile duct and the pancreatic duct enter the duodenum. It has since been termed the papilla of Vater. Under Vater's mentorship W. Amo from Guinea was the first African student who received a university doctorate. Contributed by Markus M. Lerch
19th Century
Bernard, Claude. Memoir on the Pancreas and on the Role of Pancreatic Juice in Digestive Processes. Translated by John Henderson, Academic Press, London, 1985.
Originally published in Paris, 1856.
Heidenhain, R. Beitrage zur kenntnis des pancreas. Arch Ges Physiol 10: 557, 1875.
Chiari, Hans. Über die Selbstverdauung des menschlichen Pankreas. Zeitschrift für Heilkunde 17, 69-96, 1896.
The pathologist Hans Chiari in Prague was the first to propose that pancreatitis represents a disease of autodigestion (he coined this expression) in which 'the organ succumbs to its own digestive properties.' The seminal role of digestive proteases in the pathophysiology of pancreatitis was reconfirmed when mutations in the cationic trypsinogen gene were identified as the cause of hereditary pancreatitis. Contributed by Markus M. Lerch
20th Century (First Half)
Opie, Eugene Lindsay. The relation of cholelithiasis to disease of the pancreas and to fat-necrosis. Johns Hopkins Hosp Bull 12:19-21. The etiology of acute hemorrhagic pancreatitis. Johns Hopkins Hosp Bull 12:182-188, 1901.
The New York pathologist Opie published two papers in 1901 addressing the pathophysiology of gallstone-induced pancreatitis. Both reports were based on autopsy findings and supported by carefully conducted animal experiments. The first paper suggests that obstruction of the pancreatic duct by an impacted gallstone leads to blocked pancreatic secretion and this triggers pancreatitis. The second hypothesis postulates that an impacted gallstone at the papilla creates a communication behind the stone—the so called 'common channel'—connecting the common bile duct to the pancreatic duct. Through this common channel bile acids would enter the pancreas and cause pancreatitis. The two hypotheses are mutually exclusive and have kept generations of researchers with an interest in the pathophysiology of gallstone-induced pancreatitis busy. Contributed by Markus M. Lerch
Pavlov, Ivan P. The Work of the Digestive Glands. A facsimile of the first English edition published in 1902. (First published in Russian in 1887) Oxford Historical Books, Abingdon, 1994. Full Text
Bayliss, WM and Starling, EH. The mechanism of pancreatic secretion. J Physiology 28:325-353, 1902. PMID: 16992627 Full Text
Ivy, AC and Oldberg, EA. A hormonal mechanism for gallbladder contraction and evacuation. Am J Physiology 86:599-613, 1928. Full Text
Harper, AA and Raper HS. Pancreozymin, a stimulant of the secretion of pancreatic enzymes in extracts of the small intestine. J. Physiology 102:115-125, 1943. PMID 16991584 Full Text
20th Century (Second half)
Hokin, MR and Hokin, LE. Enzyme secretion and the incorporation of P32 into phospholipides of pancreas slices. J. Biol Chem 203:967-977, 1953. PMID: 13084667 Full Text
This paper reports the original description in 1953 of the “phospholipid effect”. Hokin had developed slices of pigeon pancreas as a preparation to study secretion and metabolism and had already shown that cholinergic agonists stimulated amylase secretion. Earlier studies evaluating the incorporation of P32 into RNA had shown that the observed incorporporation was due to a hydrolytic product of phospholipids contaminating the RNA. In this paper the Hokins looked directly at the incorporation of P32 into phospholipids and showed that it was stimulated about 7 fold by carbamylcholine and other cholinergic agonists at the same time that amylase secretion was increased. This effect was blocked by atropine. They mention that similar results were obtained with duck pancreas and that similar but weaker effects were seen with slices of cerebral cortex. At this time they could not separate individual phospholipids but a few years later showed that incorporation of P32 into phosphotidylinositol was increases 15 fold and into phosphatidic acid about 3 fold. Fifteen years latter the primary event in the phospholipids effect was shown to be the break down of polyphosphoinostide. Contributed by John A. Williams
Palade, GE. The endoplasmic reticulum. J. Biophysical Biochemical Cytology 2(4, Suppl):85-98, 1956. PMID: 13357527 Full Text
Jorpes J, Mutt V. Cholecystokinin and pancreozymin, one single hormone? Acta Physiol Scand 66:196-202, 1966. PMID: 5935672
Caro, LG, Palade GE. Protein synthesis, storage and discharge in the pancreatic exocrine cell. An autoradiographic study. J. Cell Biology 20:473-495, 1964. PMID: 14128049 Full Text
Jamieson, JD, Palade GE. Intracellular transport of secretory proteins in the pancreatic acinar cell. I. Role of the peripheral elements of the Golgi complex. J Cell Biol. 34:577-596, 1967. PMID: 6035647 Full Text
Palade, G. Intracellular aspects of protein synthesis. Science 189:347-358, 1975. PMID: 1096303
This is the text of Palade's Nobel Lecture given in December 1974. It can be accessed from Science which is how it is usually cited but the text can also be accessed directly from the Nobel Foundation.
Streb, H, Irvine, RF, Berridge, MJ,and Schulz, I. Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1,4,5-trisphosphate. Nature 306:67-69, 1983. PMID: 6605482