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

被引：15

作者：

Dewan, Neelesh ^{[1
,2
]}

Shukla, Vibha ^{[1
,2
]}

Rehni, Ashish K. ^{[1
,2
]}

Koronowski, Kevin B. ^{[1
,2
,3
]}

Klingbeil, Kyle D. ^{[1
,2
]}

Stradecki-Cohan, Holly ^{[1
,2
,3
]}

Garrett, Timothy J. ^{[4
]}

Rundek, Tatjana ^{[2
,5
]}

Perez-Pinzon, Miguel A. ^{[1
,2
,3
,5
]}

Dave, Kunjan R. ^{[1
,2
,3
,5
]}

机构：

[1] Univ Miami, Sch Med, Peritz Scheinberg Cerebral Vasc Dis Res Labs, Miami, FL USA

[2] Univ Miami, Sch Med, Dept Neurol, Miami, FL USA

[3] Univ Miami, Sch Med, Neurosci Program, Miami, FL USA

[4] Univ Florida, Clin & Translat Sci Inst, Southeast Ctr Integrated Metabol, Gainesville, FL USA

[5] Univ Miami, Sch Med, Evelyn F McKnight Brain Inst, Miami, FL USA

来源：

CNS NEUROSCIENCE & THERAPEUTICS | 2020年 / 26卷 / 01期

关键词：

diabetes; enzyme kinetics; glycolysis; hippocampus; metabolomics; ANTECEDENT HYPOGLYCEMIA; L-CITRULLINE; BRAIN; GLUCOSE; GLYCOLYSIS; EXPRESSION; SUCCINATE; DAMAGE;

D O I：

10.1111/cns.13186

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：126 / 135

页数：10

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