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4447 Leptin supplementation prevents the loss of hypoglycemia-induced glucagon release following exposure to six days of severe caloric restriction in mice
- David H McDougal, Marina A. DuVall, Christopher D. Morrison, Laura A. Moldovan, Rajvi Jariwala
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- Journal:
- Journal of Clinical and Translational Science / Volume 4 / Issue s1 / June 2020
- Published online by Cambridge University Press:
- 29 July 2020, pp. 10-11
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OBJECTIVES/GOALS: We have recently shown that mice exposed to six days of 60% caloric restriction acutely display reduced hypoglycemia-induced glucagon release following refeeding, and that this effect is concurrent with low leptin levels. The current study was conducted to ascertain if leptin treatment during caloric restriction would reverse this effect. METHODS/STUDY POPULATION: Three groups of mice were used, an ad libitum (Ad-lib) fed group and two caloric restriction (CR) groups, one of which received twice daily leptin injection (0.5-1μg/g; IP) and the other vehicle (saline) during their caloric restriction. CR mice were placed on 60% caloric restriction for 6 consecutive days. Ad lib mice were housed in an identical manner but fed ad libitum during this same period. Following 6 days of restriction, CR mice were given ad lib access to food for 16 h. After the 16 h period of refeeding, both CR and ad lib mice began a 6 h fast which was immediately followed by a hypoglycemic insulin tolerance test (ITT). ITTs consisted of a variable dose of insulin intended to achieve a blood glucose of ~45 mg/dL within 60 minutes, at which time blood was collected for glucagon and corticosterone assays. RESULTS/ANTICIPATED RESULTS: The mean blood glucose levels during the ITT at 45 and 60 minutes post injection across all three groups were 46.8 + 3.1 and 37.0 + 2.4, respectively. There were no significant differences in glucose levels between the three groups at these two time points. As expected, saline treated CR mice displayed significantly reduced serum glucagon levels in response to the ITT relative to Ad-lib mice (23.5 + 10.9 vs. 91.7 + 20.8 pg/mL, p = 0.009). In contrast, leptin-treated CR mice maintained their hypoglycemia-induced glucagon response to the ITT (78.0 + 16.8 pg/mL, p>0.99 vs. Ad-lib group). In addition, although corticosterone levels in saline treated CR mice were numerically lower than in Ad-lib mice, this difference was not statistically significance (3928 + 277 vs. 4571 + 178 pg/mL, p = 0.179). DISCUSSION/SIGNIFICANCE OF IMPACT: Diabetes patients on insulin therapy often develop impaired hypoglycemic counter-regulation which can lead to life-threatening hypoglycemic complications. Our results suggest that leptin may hold promise as a therapeutic intervention for the prevention of impaired hypoglycemic counter-regulation in persons with diabetes.
Looking Backward, Looking Forward: MLA Members Speak
- April Alliston, Elizabeth Ammons, Jean Arnold, Nina Baym, Sandra L. Beckett, Peter G. Beidler, Roger A. Berger, Sandra Bermann, J.J. Wilson, Troy Boone, Alison Booth, Wayne C. Booth, James Phelan, Marie Borroff, Ihab Hassan, Ulrich Weisstein, Zack Bowen, Jill Campbell, Dan Campion, Jay Caplan, Maurice Charney, Beverly Lyon Clark, Robert A. Colby, Thomas C. Coleman III, Nicole Cooley, Richard Dellamora, Morris Dickstein, Terrell Dixon, Emory Elliott, Caryl Emerson, Ann W. Engar, Lars Engle, Kai Hammermeister, N. N. Feltes, Mary Anne Ferguson, Annie Finch, Shelley Fisher Fishkin, Jerry Aline Flieger, Norman Friedman, Rosemarie Garland-Thomson, Sandra M. Gilbert, Laurie Grobman, George Guida, Liselotte Gumpel, R. K. Gupta, Florence Howe, Cathy L. Jrade, Richard A. Kaye, Calhoun Winton, Murray Krieger, Robert Langbaum, Richard A. Lanham, Marilee Lindemann, Paul Michael Lützeler, Thomas J. Lynn, Juliet Flower MacCannell, Michelle A. Massé, Irving Massey, Georges May, Christian W. Hallstein, Gita May, Lucy McDiarmid, Ellen Messer-Davidow, Koritha Mitchell, Robin Smiles, Kenyatta Albeny, George Monteiro, Joel Myerson, Alan Nadel, Ashton Nichols, Jeffrey Nishimura, Neal Oxenhandler, David Palumbo-Liu, Vincent P. Pecora, David Porter, Nancy Potter, Ronald C. Rosbottom, Elias L. Rivers, Gerhard F. Strasser, J. L. Styan, Marianna De Marco Torgovnick, Gary Totten, David van Leer, Asha Varadharajan, Orrin N. C. Wang, Sharon Willis, Louise E. Wright, Donald A. Yates, Takayuki Yokota-Murakami, Richard E. Zeikowitz, Angelika Bammer, Dale Bauer, Karl Beckson, Betsy A. Bowen, Stacey Donohue, Sheila Emerson, Gwendolyn Audrey Foster, Jay L. Halio, Karl Kroeber, Terence Hawkes, William B. Hunter, Mary Jambus, Willard F. King, Nancy K. Miller, Jody Norton, Ann Pellegrini, S. P. Rosenbaum, Lorie Roth, Robert Scholes, Joanne Shattock, Rosemary T. VanArsdel, Alfred Bendixen, Alarma Kathleen Brown, Michael J. Kiskis, Debra A. Castillo, Rey Chow, John F. Crossen, Robert F. Fleissner, Regenia Gagnier, Nicholas Howe, M. Thomas Inge, Frank Mehring, Hyungji Park, Jahan Ramazani, Kenneth M. Roemer, Deborah D. Rogers, A. LaVonne Brown Ruoff, Regina M. Schwartz, John T. Shawcross, Brenda R. Silver, Andrew von Hendy, Virginia Wright Wexman, Britta Zangen, A. Owen Aldridge, Paula R. Backscheider, Roland Bartel, E. M. Forster, Milton Birnbaum, Jonathan Bishop, Crystal Downing, Frank H. Ellis, Roberto Forns-Broggi, James R. Giles, Mary E. Giles, Susan Blair Green, Madelyn Gutwirth, Constance B. Hieatt, Titi Adepitan, Edgar C. Knowlton, Jr., Emanuel Mussman, Sally Todd Nelson, Robert O. Preyer, David Diego Rodriguez, Guy Stern, James Thorpe, Robert J. Wilson, Rebecca S. Beal, Joyce Simutis, Betsy Bowden, Sara Cooper, Wheeler Winston Dixon, Tarek el Ariss, Richard Jewell, John W. Kronik, Wendy Martin, Stuart Y. McDougal, Hugo Méndez-Ramírez, Ivy Schweitzer, Armand E. Singer, G. Thomas Tanselle, Tom Bishop, Mary Ann Caws, Marcel Gutwirth, Christophe Ippolito, Lawrence D. Kritzman, James Longenbach, Tim McCracken, Wolfe S. Molitor, Diane Quantic, Gregory Rabassa, Ellen M. Tsagaris, Anthony C. Yu, Betty Jean Craige, Wendell V. Harris, J. Hillis Miller, Jesse G. Swan, Helene Zimmer-Loew, Peter Berek, James Chandler, Hanna K. Charney, Philip Cohen, Judith Fetterley, Herbert Lindenberger, Julia Reinhard Lupton, Maximillian E. Novak, Richard Ohmann, Marjorie Perloff, Mark Reynolds, James Sledd, Harriet Turner, Marie Umeh, Flavia Aloya, Regina Barreca, Konrad Bieber, Ellis Hanson, William J. Hyde, Holly A. Laird, David Leverenz, Allen Michie, J. Wesley Miller, Marvin Rosenberg, Daniel R. Schwarz, Elizabeth Welt Trahan, Jean Fagan Yellin
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- Journal:
- PMLA / Publications of the Modern Language Association of America / Volume 115 / Issue 7 / December 2000
- Published online by Cambridge University Press:
- 23 October 2020, pp. 1986-2078
- Print publication:
- December 2000
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