Exposure to recurrent hypoglycemia alters hippocampal metabolism in treated streptozotocin-induced diabetic rats

Neelesh Dewan, Vibha Shukla, Ashish K. Rehni, Kevin B. Koronowski, Kyle D. Klingbeil, Holly Stradecki-Cohan, Timothy J. Garrett, Tatjana Rundek, Miguel A. Perez-Pinzon, Kunjan R. Dave

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Aims: Exposure to recurrent hypoglycemia (RH) is common in diabetic patients receiving glucose-lowering therapies and is implicated in causing cognitive impairments. Despite the significant effect of RH on hippocampal function, the underlying mechanisms are currently unknown. Our goal was to determine the effect of RH exposure on hippocampal metabolism in treated streptozotocin-diabetic rats. Methods: Hyperglycemia was corrected by insulin pellet implantation. Insulin-treated diabetic (ITD) rats were exposed to mild/moderate RH once a day for 5 consecutive days. Results: The effect of RH on hippocampal metabolism revealed 65 significantly altered metabolites in the RH group compared with controls. Several significant differences in metabolite levels belonging to major pathways (eg, Krebs cycle, gluconeogenesis, and amino acid metabolism) were discovered in RH-exposed ITD rats when compared to a control group. Key glycolytic enzymes including hexokinase, phosphofructokinase, and pyruvate kinase were affected by RH exposure. Conclusion: Our results demonstrate that the exposure to RH leads to metabolomics alterations in the hippocampus of insulin-treated streptozotocin-diabetic rats. Understanding how RH affects hippocampal metabolism may help attenuate the adverse effects of RH on hippocampal functions.

Original languageEnglish (US)
Pages (from-to)126-135
Number of pages10
JournalCNS Neuroscience and Therapeutics
Issue number1
StatePublished - Jan 1 2020
Externally publishedYes


  • diabetes
  • enzyme kinetics
  • glycolysis
  • hippocampus
  • metabolomics

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Physiology (medical)
  • Pharmacology (medical)
  • Pharmacology


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