Hypoglycemia increases glycolytic metabolism in the rat ventromedial hypothalamus (VMH)

Abstract

The VMH is a critical brain‐area involved in energy sensing and responsible for initiating the counter regulatory response (CRR) during hypoglycemia. We hypothesize local metabolic changes following hypoglycemia contribute to hypoglycemia‐associated autonomic failure (HAAF), an impairment of the CRR. VMH and CA1 hippocampus (HPC) were collected from rats (n=30) 6 hours following a single episode of insulin‐induced hypoglycemia (IIH) (acute hypoglycemia; AH), 24 h following the third of 3 recurrent episodes of IIH (recurrent hypoglycemia; RH), or saline‐treated euglycemia (control; SC). Tissue samples were randomly pooled before methanol extraction and analysis by GC/MS and LC/MS/MS. 180 metabolites were identified and quantified. In the VMH lactate, tricarboxylic acid (TCA) cycle intermediates (citrate, cis‐aconitate, and malate), and phospholipid metabolism products (glycerol and glycerol‐3‐phosphate) were increased (p≤0.05) 6 h following AH, but were not significantly different 24 h after RH. These changes were not observed in HPC following IIH. RNA sequencing analysis showed a 0.9, 0.2, and 0.1 fold‐increase in glycerol‐3‐phosphate dehydrogenase, GLUT1, and 2‐oxoglutarate dehydrogenase gene expression, respectively (p≤0.01), in the VMH 24 h after RH. It is unclear at this time whether the hypoglycemia‐induced changes in carbohydrate and lipid metabolism in the VMH contribute to HAAF. Supported by DK082609