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November 17, 2023
Case of the Month The RECNAC II Project by Michael Gonzalez, Ph.D
Exercise-Induced GLP-1 Secretion Ninety minutes of exercise in mice induces a 2.5-fold increase in plasma active GLP-1, mediated by skeletal-muscle-derived IL-6, as shown by abolishing exercise-induced active GLP-1 levels in Il6 / mice and by treating wild-type mice with an antibody to IL-6 ( Gcg and Pcsk1 mRNA, but not plasma GLP-2 (ELISA) or DPP4 activity ( Gcg mRNA, chronic IL-6 treatment does not increase plasma GLP-2 levels suggesting a difference in GLP-1 and GLP-2 transcript or protein stability
USA 102 , 23102315 (2005)
They also highlight a recurring pattern in peptide drug development: early safety signals, particularly those observed at supraphysiologic exposure levels or in non-human models, have frequently led to premature abandonment of otherwise biologically compelling targets
