title: Sex-specific basal and hypoglycemic patterns of in vivo caudal dorsal vagal complex astrocyte glycogen metabolic enzyme protein expression.
abstract: Astrocytes contribute to neurometabolic stability through uptake, catabolism, and storage of glucose. These cells maintain the major brain glycogen reservoir, which is a critical fuel supply to neurons during glucose deficiency and increased brain activity. We used a combinatory approach incorporating immunocytochemistry, laser microdissection, and Western blotting to investigate the hypothesis of divergent expression of key enzymes regulating glycogen metabolism and glycolysis during in vivo normo- and/or hypoglycemia in male versus female hindbrain astrocytes. Glycogen synthase (GS) and glycogen phosphorylase (GP) levels were both enhanced in dorsal vagal complex astrocytes from vehicle-injected female versus male controls, with incremental increase in GS exceeding GP. Insulin-induced hypoglycemia (IIH) diminished GS and increased glycogen synthase kinase-3-beta (GSK3β) expression in both sexes, but decreased phosphoprotein phosphatase-1 (PP1) levels only in males. Astrocyte GP content was elevated by IIH in male, but not female rats. Data reveal sex-dependent sensitivity of these enzyme proteins to lactate as caudal hindbrain repletion of this energy substrate fully or incompletely reversed hypoglycemic inhibition of GS and prevented hypoglycemic augmentation of GSK3β and GP in females and males, respectively. Sex dimorphic patterns of glycogen branching and debranching enzyme protein expression were also observed. Levels of the rate-limiting glycolytic enzyme, phosphofructokinase, were unaffected by IIH with or without lactate repletion. Current data demonstrating sex-dependent basal and hypoglycemic patterns of hindbrain astrocyte glycogen metabolic enzyme expression imply that glycogen volume and turnover during glucose sufficiency and shortage may vary accordingly.
authors.affiliation: Department of Basic Pharmaceutical Sciences, College of Pharmacy, The University of Louisiana at Monroe, Monroe, LA 71201, United States.
authors.forename: Pratistha
authors.initials: P
authors.lastname: Tamrakar
authors.affiliation: Department of Basic Pharmaceutical Sciences, College of Pharmacy, The University of Louisiana at Monroe, Monroe, LA 71201, United States.
authors.forename: Prem
authors.initials: P
authors.lastname: Shrestha
authors.affiliation: Department of Basic Pharmaceutical Sciences, College of Pharmacy, The University of Louisiana at Monroe, Monroe, LA 71201, United States. Electronic address: briski@ulm.edu.
authors.forename: Karen P
authors.initials: KP
authors.lastname: Briski
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000201:enzymology*; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D024981:Glycogen Phosphorylase / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism*; D007003:Hypoglycemia / Q000473:pathology*; D008297:Male; D042282:Microdissection; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D017552:Solitary Nucleus / Q000473:pathology*
chemical_list: D001786:Blood Glucose; D024981:Glycogen Phosphorylase; D006006:Glycogen Synthase; D010751:Phosphopyruvate Hydratase
keywords: Glial fibrillary acidic protein; Glycogen phosphorylase; Glycogen synthase; Insulin-induced hypoglycemia; Laser-catapult microdissection