Digestive Enzymes Escape

During a Meal


A single meal can lead to digestive enzyme activity in the circulation causing proteolytic membrane receptor cleavage even in healthy volunteers.


Augusta. E. Modestino, PhD a,b, Elaine. A. Skowronski, PhD c, Chris Pruitt d, Pam Taub, MD e, Karen Herbst, MD f, Geert W. Schmid-Schönbein, PhDa, Michael. J. Heller, PhD a,b, Paul. J. Mills, PhDd *.

aDepartment of Bioengineering, University of California San Diego, La Jolla, CaliforniabKnight Cancer Center, Center for Early Cancer Detection (CEDAR), Oregon Health Sciences University, Portland, OregoncDepartment of Nanoengineering, University of California San Diego, La Jolla, CaliforniadDepartment of Family Medicine and Public Health, University of California San Diego, La Jolla, Californiae Department of Medicine, University of California San Diego, La Jolla Californiaf Department of Medicine, The University of Arizona Health Sciences, Tucson, Arizona
Abstract: Objective: To examine resting and post-prandial peripheral protease activity in healthy controls and individuals with type 2 diabetes mellitus (T2DM) and pre-T2DM. Methods: Individuals with T2DM or pre-T2DM and healthy controls (mean age 55.8 years) were studied before and for a span of 300 minutes following a single high-calorie McDonald’s breakfast. Metalloproteases-2/-9 (MMP-2/-9), elastase, and trypsin activities were assessed in whole blood before and following the meal using a novel high-precision electrophoretic platform. Also assessed were circulating levels of inflammatory biomarkers and insulin receptor density on peripheral blood mononuclear cells (PBMC) in relationship to protease activity. Results: Pre-meal MMP-2/-9 and elastase activity levels in T2DM and in pre-T2DM participants were significantly elevated as compared to controls. The T2DM group showed a significant increase in elastase activity 15 minutes after the meal; elastase activity continued to increase to the 30-minute time point (p<0.01). In control participants, MMP-2/-9, elastase, and trypsin were significantly increased at 15 minutes after the meal (p<0.05) and returned back to pre-meal values within a period of approximately 30 to 60 minutes post-meal. PBMCs incubated for one hour with plasma from T2DM and pre-T2DM had significantly lower levels of insulin receptor density compared to those incubated with plasma from control participants (p<0.001). Conclusions: The results of this exploratory study suggest that individuals with T2DM and pre-T2DM have higher resting systemic protease activity than non-symptomatic controls. A single high-calorie / high-carbohydrate mealresults in further elevations of protease activity in the systemic circulation of T2DM and pre-T2DM, as well as in healthy controls. The protease activity in turn can lead to a down-regulation of insulin receptor density, potentially supporting a state of insulin resistance.
J. Am. Coll. Nutition, In press, 2018