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Robert K. Crane

    Robert Kellogg Crane (born June 12, 1924) is an American biochemist best known for his discovery of sodium-glucose cotransport.

    Biography

    Robert Kellogg Crane was born on December 20, 1919 in Palmyra, New Jersey, to Wilbur Fiske Crane, architect and engineer, and Mary Elisabeth Crane. He is the grandson of Stephen Crane's brother Wilbur.Robert K. Crane. "Stephen Crane's Family Heritage". Stephen Crane Studies 4.1, 1995.
    After serving in the in the Navy during World War II, Crane studied in biochemistry with Eric Ball at Harvard from 1946 to 1949, then spent a year with Fritz Lipmann at Harvard Medical School, and received a Ph.D. in Medical Sciences in 1950. He then joined Carl Cori’s Department of Biological Chemistry at Washington University School of Medicine in St. Louis, where he began his long interest in glucose metabolism and worked until 1962. After that, he was professor and chairman of the department of Biochemistry at the Chicago Medical School and then held the same positions at Rutgers Medical School until 1986.Robert K. Crane. “The road to ion-coupled membrane processes. In: Comprehensive Biochemistry”. Vol 35: Selected Topics in the History of Biochemistry, Personal Recollections l. (Neuberger, A., van Deenen, L. L. M. and Semenga, G., Eds.), Elsevier, Amsterdam, 1983, pp. 43-69.
    He received the American Gastroenterological Association’s Distinguished Achievement Award in 1969

    Discovery of cotransport

    In the 1950’s, Crane played a central role in establishing that glucose transport into the cell was the first step in glucose metabolism and its control. He demonstrated that neither the phosphorylation-dephosphorylation nor other covalent reactions accounted for glucose transport in the intestine.
    In August 1960, in Prague, Crane presented for the first time his discovery of the sodium-glucose cotransport as the mechanism for intestinal glucose absorption.Robert K. Crane, D. Miller and I. Bihler. “The restrictions on possible mechanisms of intestinal transport of sugars”. In: Membrane Transport and Metabolism. Proceedings of a Symposium held in Prague, August 22–27, 1960. Edited by A. Kleinzeller and A. Kotyk. Czech Academy of Sciences, Prague, 1961, pp. 439-449. This discovery was the most important event concerning carbohydrate absorption in the 20th century.Ernest M. Wright. “Genetic disorders of membrane transport: Glucose-galactose malabsorption”. A J P - Gastrointest Liver Physiol 275:879-882, 1998, p. G879. “In the 1960s, two milestones were reached in the physiology of intestinal sugar absorption. The first was the Na+ -glucose cotransport hypothesis of Crane and colleagues, which explained active sugar transport”Boyd, C A R. “Facts, fantasies and fun in epithelial physiology”. Experimental Physiology, Volume 93, Issue 3, 2008, p. 304. “the insight from this time that remains in all current text books is the notion of Robert Crane published originally as an appendix to a symposium paper published in 1960 (Crane et al. 1960). The key point here was 'flux coupling', the cotransport of sodium and glucose in the apical membrane of the small intestinal epithelial cell. Half a century later this idea has turned into one of the most studied of all transporter proteins (SGLT1), the sodium–glucose cotransporter.”

    Application in oral rehydration therapy

    Crane’s discovery of cotransport led directly to the development of oral rehydration therapy. This treatment counter-balances the loss of water and electrolytes caused by cholera via a glucose containing salt solution that accelerates water and electrolyte absorption. This is possible because cholera does not interfere with sodium-glucose cotransport. Arthur C Guyton and John E Hall. “Textbook of Medical Physiology”. Elsevier Saunders, Philadelphia, 2006, pp. 814-816.Canadian Paediatric Society, Nutrition Committee. = 2009-02-17 “Oral rehydration therapy and early refeeding in the management of childhood gastroenteritis”.] Paediatrics & Child Health, volume 11, issue 8, 2006, pp. 527-531.
    Oral rehydration therapy saves the lives of millions of cholera patients in underdeveloped countries since the 1980’s. W.B. Greenough. Lancet 345, June 1995, p. 1568. “The life saving power of oral rehydration therapy was first demonstrated in cholera patients. By 1971 there was sufficient knowledge to reduce death from 40% to less than 3%, even under chaotic field conditions ----- ‘Now used for all diarrheal diseases it’ saves the lives of over one million children a year and if fully used could save 3-4 million lives every year.” It is one of the most important medical advances of the 20th century. Editorial. “Water with sugar and salt”. Lancet 2, August 5, 1978, pp. 300–301. “The discovery that sodium transport and glucose transport are coupled in the small intestine, so that glucose accelerates absorption of solute and water, was potentially the most important medical advance this century.”Michael Seear. “An Introduction to International Health”. Canadian Scholars' Press, 2007, p. 175. “In terms of numbers of children saved, the discovery of oral rehydration solution is one of greatest medical advances of all time.”

    Applications in pharmaceutical drugs

    Crane’s discovery is also used in block buster drugs, such as the SSRI Prozac, which treat depression by inhibiting the Na/serotonin cotransporters in the brain.
    Furthermore, major pharmaceutical companies are developing inhibitors of the Na/glucose cotransporters to treat diabetes and obesity. “High Rider Reaches Agreement in Principal with French Biopharmaceutical Company”. PR Newswire, October 9, 2007. “High Rider Capital Inc. (…) [1] develop a chemical process to achieve synthesis of a new class of Sodium Glucose Cotransporters inhibitors (…), for the treatment of Type 2 Diabetes, obesity and other possible metabolic syndrome applications.”

    Selected Bibliography

    • Robert K. Crane and T. Hastings Wilson. “In vitro method for the study of the rate of intestinal absorption of sugars”. Journal of Applied Physiology, volume 12, 1958, pp. 145-146.
    • Robert K. Crane. “Intestinal absorption of sugars”. Physiological Reviews, volume 40, 1960, pp. 789–825.
    • Robert K. Crane, D. Miller and I. Bihler. “The restrictions on possible mechanisms of intestinal transport of sugars”. In: Membrane Transport and Metabolism. Proceedings of a Symposium held in Prague, August 22–27, 1960. Edited by A. Kleinzeller and A. Kotyk. Czech Academy of Sciences, Prague, 1961, pp. 439-449.
    • D. Miller and Robert K. Crane. “The digestive function of epithelium of the small intestine. 1. An intracellular locus of disaccharide and sugar phosphate ester hydrolysis”. Biochimica et Biophysica Acta 52, 1961, pp. 281-293.
    • Robert K. Crane. “Hypothesis for mechanism of intestinal active transport of sugars” Federation Proc. 21, 1962, pp. 891-895.
    • Alexander Eichholz, K.E. Howell and Robert K. Crane. “Studies on the organization of the brush border in intestinal epithelial cells VI. Glucose binding to isolated intestinal brush borders and their subfractions”. Biochimica et Biophysica Acta 193, 1969, pp. 179-192.
    • Robert K. Crane. “Structural and functional organization of an epithelial cell brush border”. Intracellular Transport, Symp. Intnl. Soc. Cell BioI. Volume 5, B. Warren, Ed., Academic Press, 1966, pp. 71-102
    • Alexander Eichholz and Robert K. Crane. “Isolation of plasma membranes from intestinal brush borders in Methods in Enzymology”. Volume 31, part A, Biomembranes, S. Fleischer and L. Packer, Eds., Academic Press, 1974, pp. 123-134.
    • Robert K. Crane. “The gradient hypothesis and other models of carrier-mediated active transport” Reviews of Physiology, Biochemistry and Pharmacology, volume 78, 1977, pp. 99-159.
    • Robert K. Crane. “Digestion and absorption: water-soluble organics”. International review of physiology, Gastrointestinal physiology II, volume 12, Robert K. Crane, Ed., University Park Press, 1977, pp. 325-365.
    • Robert K. Crane. “The road to ion-coupled membrane processes.” In: Comprehensive Biochemistry. Vol 35: Selected Topics in the History of Biochemistry, Personal Recollections l. (Neuberger, A., van Deenen, L. L. M. and Semenga, G., Eds.), Elsevier, Amsterdam, 1983, pp. 43-69.

    Further reading

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    References