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SUGAR METABOLISM AND DIABETES.

SUGAR METABOLISM AND DIABETES. When Pawlow demonstrated that pancreatic juice as secreted into the intestine in an inactive form is rendered active by another ferment, enterokinase, secreted by the intestinal mucosa, he did more than give a new light on the processes of digestion in the intestine, important as that contribution was. He also pointed the way to new researches that might show other examples of the interdependence of organs and cells. One of the fruits of this research seems to have matured in the very important discovery of O. Cohnheim1 concerning the mechanism and the agents concerned in sugar metabolism, apparently a discovery that clears up at last one of the most fundamental processes of metabolism which has evaded solution in spite of much work directed to that end. It is indeed strange that the history of sugar in the body has not been completely worked out long ago, in view of our familiarity with its chemical properties and structure, and the large quantities that the body daily utilizes. We have long been familiar with certain steps in its metabolism, knowing that in whatever form it is ingested it is absorbed as a monosaccharid; that a fairly constant amount is maintained in the blood through the ability of the liver and muscles to convert any excess into glycogen and to restore it whenever there begins to be a deficiency; and also that if the sugar in the blood greatly exceeds the normal amount it begins to escape into the urine. We also knew that sugar was the chief source of heat and energy, which it furnished by undergoing destructive oxidation; and as the chief place where heat and energy is produced is in the muscles it was probable that the oxidation took place within the muscle cells. Yet experimentally it had not been possible to demonstrate any such property in muscle tissue. It was known that glycolytic ferments exist that have the power of destroying sugar, but extracts prepared from muscles in various ways were found to have no such property, or at least not enough to begin to account for the enormous destruction of sugar that the body accomplishes every day. And so, despite the apparent certainty that the muscle tissue was the seat of an active glycolysis during life, the agents concerned could not be found within them by experimental means. Another set of facts implicated the pancreas, beginning with the classical observations of von Mering and Minkowski that removal of the pancreas led to severe glycosuria in the lower animals, up to the recent observations of our American scientists—Opie showing that of the different elements of the pancreas, the islands of Langerhans are the chief and probably the sole structure concerned in human diabetes, and Herter, that reducing bodies of any kind applied to the pancreas cause the appearance of sugar in the urine. It was also known that in animals in which the pancreas is thrown out of function, as well as in human pancreatic diabetes, the sugar accumulates in the blood instead of being oxidized, and from this accumulation results the glycosuria. Evidently, then, the pancreas is essential for the oxidation of sugar, and it might well be imagined that among the many enzymes it produces is one that has this property, but as with the muscles it has been impossible to demonstrate any such enzyme in the pancreas. It remained for Cohnheim to put these facts together; considering the peculiar change brought about in a pancreatic zymogen, trypsinogen, by the action of another ferment contained in the succus entericus, whereby the inactive zymogen is converted into trypsin, he came to appreciate the possibility of some similar interrelation of pancreas and muscles. Experiments were made along the lines thus suggested, with most successful results. It was readily demonstrated that although extracts of either pancreas or of muscle made by expressing the juices of the cells by a powerful press, were practically without effect on glucose when each was taken alone, yet when combined the resulting mixture was able to destroy the sugar rapidly and in time completely. Furthermore, the amount and rate of glycolysis shown by muscle extract is sufficient to account fully for all the oxidation of sugar accomplished by the body during the day. Putting together all the facts now acquired it would seem that in the islands of Langerhans is formed a substance which is like a ferment in nature, as it is destroyed by heat. This substance passing to the muscles through the blood stream meets in the muscle cells another ferment or proferment, and between them a reaction occurs resulting in the formation of a ferment that has the power of rapidly destroying sugar. . . . As Cohnheim's results, which seem to be unquestionable, are amplified, and we know more about the intermediate steps and the places of normal glycosis, as well as the nature of the pancreatic and the muscle agents implicated, it is probable that we shall understand better than was possible before the essentials of the pathogenesis of human diabetes. Perhaps the most remarkable thing about Cohnheim's discovery is its simplicity, the usual characteristic of real discoveries. For years physiologic chemists have been trying to put the sugar destruction on the pancreas or on the muscles, knowing each to be concerned, but in vain. Why it had not before occurred to any one that it might be the work of the two together is the chief mystery. Now that the suggestion has been made and followed out the entire difficulty clears up, and we have a most reasonable and simple explanation of a long perplexing problem, as well as a new field for fruitful research. JAMA. 1903;41:1480-1481 1. Hoppe-Seyler's Zeitschrift f. Physiol. Chemie, 1903, xxxix, 336. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA American Medical Association

SUGAR METABOLISM AND DIABETES.

JAMA , Volume 290 (22) – Dec 10, 2003

SUGAR METABOLISM AND DIABETES.

Abstract

When Pawlow demonstrated that pancreatic juice as secreted into the intestine in an inactive form is rendered active by another ferment, enterokinase, secreted by the intestinal mucosa, he did more than give a new light on the processes of digestion in the intestine, important as that contribution was. He also pointed the way to new researches that might show other examples of the interdependence of organs and cells. One of the fruits of this research seems to have matured in the very...
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Publisher
American Medical Association
Copyright
Copyright © 2003 American Medical Association. All Rights Reserved.
ISSN
0098-7484
eISSN
1538-3598
DOI
10.1001/jama.290.22.3010
Publisher site
See Article on Publisher Site

Abstract

When Pawlow demonstrated that pancreatic juice as secreted into the intestine in an inactive form is rendered active by another ferment, enterokinase, secreted by the intestinal mucosa, he did more than give a new light on the processes of digestion in the intestine, important as that contribution was. He also pointed the way to new researches that might show other examples of the interdependence of organs and cells. One of the fruits of this research seems to have matured in the very important discovery of O. Cohnheim1 concerning the mechanism and the agents concerned in sugar metabolism, apparently a discovery that clears up at last one of the most fundamental processes of metabolism which has evaded solution in spite of much work directed to that end. It is indeed strange that the history of sugar in the body has not been completely worked out long ago, in view of our familiarity with its chemical properties and structure, and the large quantities that the body daily utilizes. We have long been familiar with certain steps in its metabolism, knowing that in whatever form it is ingested it is absorbed as a monosaccharid; that a fairly constant amount is maintained in the blood through the ability of the liver and muscles to convert any excess into glycogen and to restore it whenever there begins to be a deficiency; and also that if the sugar in the blood greatly exceeds the normal amount it begins to escape into the urine. We also knew that sugar was the chief source of heat and energy, which it furnished by undergoing destructive oxidation; and as the chief place where heat and energy is produced is in the muscles it was probable that the oxidation took place within the muscle cells. Yet experimentally it had not been possible to demonstrate any such property in muscle tissue. It was known that glycolytic ferments exist that have the power of destroying sugar, but extracts prepared from muscles in various ways were found to have no such property, or at least not enough to begin to account for the enormous destruction of sugar that the body accomplishes every day. And so, despite the apparent certainty that the muscle tissue was the seat of an active glycolysis during life, the agents concerned could not be found within them by experimental means. Another set of facts implicated the pancreas, beginning with the classical observations of von Mering and Minkowski that removal of the pancreas led to severe glycosuria in the lower animals, up to the recent observations of our American scientists—Opie showing that of the different elements of the pancreas, the islands of Langerhans are the chief and probably the sole structure concerned in human diabetes, and Herter, that reducing bodies of any kind applied to the pancreas cause the appearance of sugar in the urine. It was also known that in animals in which the pancreas is thrown out of function, as well as in human pancreatic diabetes, the sugar accumulates in the blood instead of being oxidized, and from this accumulation results the glycosuria. Evidently, then, the pancreas is essential for the oxidation of sugar, and it might well be imagined that among the many enzymes it produces is one that has this property, but as with the muscles it has been impossible to demonstrate any such enzyme in the pancreas. It remained for Cohnheim to put these facts together; considering the peculiar change brought about in a pancreatic zymogen, trypsinogen, by the action of another ferment contained in the succus entericus, whereby the inactive zymogen is converted into trypsin, he came to appreciate the possibility of some similar interrelation of pancreas and muscles. Experiments were made along the lines thus suggested, with most successful results. It was readily demonstrated that although extracts of either pancreas or of muscle made by expressing the juices of the cells by a powerful press, were practically without effect on glucose when each was taken alone, yet when combined the resulting mixture was able to destroy the sugar rapidly and in time completely. Furthermore, the amount and rate of glycolysis shown by muscle extract is sufficient to account fully for all the oxidation of sugar accomplished by the body during the day. Putting together all the facts now acquired it would seem that in the islands of Langerhans is formed a substance which is like a ferment in nature, as it is destroyed by heat. This substance passing to the muscles through the blood stream meets in the muscle cells another ferment or proferment, and between them a reaction occurs resulting in the formation of a ferment that has the power of rapidly destroying sugar. . . . As Cohnheim's results, which seem to be unquestionable, are amplified, and we know more about the intermediate steps and the places of normal glycosis, as well as the nature of the pancreatic and the muscle agents implicated, it is probable that we shall understand better than was possible before the essentials of the pathogenesis of human diabetes. Perhaps the most remarkable thing about Cohnheim's discovery is its simplicity, the usual characteristic of real discoveries. For years physiologic chemists have been trying to put the sugar destruction on the pancreas or on the muscles, knowing each to be concerned, but in vain. Why it had not before occurred to any one that it might be the work of the two together is the chief mystery. Now that the suggestion has been made and followed out the entire difficulty clears up, and we have a most reasonable and simple explanation of a long perplexing problem, as well as a new field for fruitful research. JAMA. 1903;41:1480-1481 1. Hoppe-Seyler's Zeitschrift f. Physiol. Chemie, 1903, xxxix, 336.

Journal

JAMAAmerican Medical Association

Published: Dec 10, 2003

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