Summary of project PR001037

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR001037. The data can be accessed directly via it's Project DOI: 10.21228/M8NM4H This work is supported by NIH grant, U2C- DK119886.


Project ID: PR001037
Project DOI:doi: 10.21228/M8NM4H
Project Title:NMR and MS Metabolomics Reveal a Distinct Metabolic State of Ricin-induced Hypoglycemia
Project Type:Targeted NMR and Untargeted MS
Project Summary:Ricin toxin is a ribosome inactivating protein. Due to its toxic and chemical properties, ricin is a potential agent of bioterrorism but has also been studied for therapeutic use in immunotoxins. Previous research by our group has demonstrated lethal hypoglycemia associated with ricin toxicity. Research efforts have focused on better understanding this ricin-induced metabolic state of hypoglycemia to aid in better understanding the systemic effects of hypoglycemia, and the use of ricin in immunotherapy. Here, we have used a mouse model to characterize liver metabolome changes associated with hypoglycemia induced by two conditions. Mice were challenged with intraperitoneal injections of ricin at high and low doses for 2 hrs, 8 hrs, and overnight. To understand how ricin-induced hypoglycemia differs from that of fasting, another group of mice had food withheld for 8-hours and overnight. 1H NMR-based metabolomics was performed on polar molecules extracted from mouse livers, with metabolites annotated using Chenomx software. MetaboAnalyst was employed for multivariate statistical analysis. In this study, similar decreases in blood glucose in mice were observed following injection of a lethal dose of ricin and with overnight fasting. NMR analyses identified 59 polar metabolites present in mice livers from all treatments. Multivariate statistical analyses were used to evaluate global metabolic state differences. Results from these analyses indicated that the profiled liver metabolomes for mice subjected to the two conditions differ significantly at both 8 hours and overnight. Additionally, ricin treatment with a lethal dose reveal a progression of metabolic changes over time, from 2 to 22 hours. Additionally, mass spectrometry supported these findings, and NMR analyses revealed key metabolites that contribute to these differences. While both ricin and fasting induce hypoglycemia, the metabolic states resulting from these two conditions are different. Further analyses may give insights into mechanisms of ricin toxicity, specific metabolic pathways that are altered, and potential treatments for hypoglycemia. We propose to extend these studies to insulin-induced hypoglycemia.
Institute:Montana State University
Department:Chemistry & Biochemistry
Last Name:Kempa
First Name:Jake
Address:103 Chemistry and Biochemistry Building, Bozeman, Montana, 59717, USA

Summary of all studies in project PR001037

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : Contains raw data)
ST001614 NMR metabolomics analysis of ricin-induced and fasting hypoglycemia (part-I) Mus musculus Montana State University NMR 2022-11-29 1 107 Uploaded data (104.3M)*
ST001667 LC-MS metabolomics analysis of ricin-induced and fasting hypoglycemia (part-II) Mus musculus Montana State University MS* 2022-11-29 1 108 Uploaded data (8.5G)*