Increased capacity for glycogen turnover in the rat ventromedial hypothalamus (VMH) following hypoglycemia (LB449)

Abstract

Recurrent hypoglycemia impairs the ability of the VMH to initiate a counterregulatory response and contributes to hypoglycemia‐associated autonomic failure (HAAF). We hypothesize that mobilization of VMH glycogen during and following hypoglycemia interferes with local glucose sensing and that genes associated with increased glycogen turnover will be upregulated after single and recurrent episodes of hypoglycemia. VMH were dissected from rats (N=23) 6 h after a single episode of insulin‐induced hypoglycemia (IIH) (acute), 24 h after the third of 3 recurrent episodes of IIH (recurrent), and saline‐treated euglycemia (control). RNA was extracted for RNA sequencing and real time‐PCR (RT‐PCR) analysis for glucose metabolism genes. One‐way ANOVA identified genes with statistically significant expression changes between treatments, principal component (PC) analysis of significantly different genes separated data points by treatment group, and genes significantly correlated with the PCs were identified. Glycogen synthase, phosphorylase kinase, glycogen phosphorylase, and UDP‐glucose pyrophosphorylase were significantly increased after acute hypoglycemia compared to control in the RT‐PCR analysis. Glycogen phosphorylase was upregulated in the acute treatment groups from both RNAseq and RT‐PCR compared to control and showed sustained elevation in the recurrent treatment from RT‐PCR analysis. These data provide evidence supporting the hypothesis that glycogen metabolism contributes to impaired glucose counterregulation and identify genes that are associated with novel hypotheses for future exploration. Supported by DK082609Grant Funding Source: DK082609