Astrocyte Glucose-6-phosphorylase-Beta regulates ventromedial hypothalamic nucleus glucose counterregulatory neurotransmission and systemic hormone profiles

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides Pub Date : 2025-03-18 DOI:10.1016/j.npep.2025.102519

Karen P. Briski, Sushma Katakam, Subash Sapkota, Madhu Babu Pasula, Rami Shrestha, Rajesh Vadav

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引用次数: 0

Abstract

Brain astrocytes generate free glucose at the conclusion of glycogenolysis or gluconeogenesis by glucose-6-phosphatase-beta (Glc-6-Pase-β) hydrolytic action. Astrocytes shape ventromedial hypothalamic nucleus (VMN) control of glucose counterregulation via lactate provision, yet possible effects of astrocyte endogenous glucose production are unknown. Current research investigated eu- and hypoglycemic patterns of VMN neuron counterregulatory neurotransmitter marker protein expression and counterregulatory hormone secretion following in vivo VMN astrocyte Glc-6-Pase-β gene-knockdown. Gene-silencing caused reductions in VMN astrocyte Glc-6-Pase-β protein expression and tissue glycogen and glucose content. Hypoglycemic suppression (dorsomedial VMN; VMNdm) or augmentation (ventrolateral VMN; VMNvl) of glycogen involves Glc-6-Pase-β –independent versus -dependent mechanisms, respectively. siRNA pretreatment reversed hypoglycemic down-regulation of VMNdm glucose levels and intensified up-regulated VMNvl glucose accumulation. Glc-6-Pase-β gene-knockdown correspondingly suppressed or enhanced baseline expression of glutamate decarboxylase_65/67 (GAD) and neuronal nitric oxide synthase (nNOS), protein markers for the counterregulation-inhibiting or -enhancing neurochemicals γ-aminobutyric acid and nitric oxide. Glc-6-Pase-β siRNA pretreatment did not alter hypoglycemic suppression of VMN GAD protein but reversed (VMNdm) or amplified (VMNvl) nNOS up-regulation. VMN Glc-6-Pase-β gene-silencing attenuated hypoglycemic patterns of corticosterone and growth hormone secretion and enhanced glucagon release. In summary, data provide unique evidence that VMN Glc-6-Pase-β activity affects glucose counterregulation. Outcomes document astrocyte Glc-6-Pase-β control of VMN glucose and glycogen accumulation as well as VMN neuron counterregulatory neurotransmission. Further research is warranted to identify Glc-6-Pase-β – mediated adjustments in astrocyte glucose metabolism that affect VMN GABAergic and/or nitrergic signaling within the brain glucostatic circuitry.

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来源期刊

Neuropeptides 医学-内分泌学与代谢

CiteScore

5.40

自引率

6.90%

发文量

审稿时长

>12 weeks

期刊介绍： The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems. The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.