Hindbrain catecholamine regulation of ventromedial hypothalamic nucleus glycogen metabolism during acute versus recurring insulin-induced hypoglycemia in male versus female rat
| Autor: | Khaggeswar Bheemanapally, Mostafa M.H. Ibrahim, Karen P. Briski, Ayed A. Alshamrani, Prabhat R. Napit, Abdulrahman Alhamyani, Ali Md Haider |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism 6-hydroxydopamine Hypoglycemia Article Diseases of the endocrine glands. Clinical endocrinology Glycogen phosphorylase Norepinephrine chemistry.chemical_compound Endocrinology Internal medicine Sex differences medicine Recurrent insulin-induced hypoglycemia Neurotransmitter Glycogen synthase Diminution biology Glycogen RC648-665 medicine.disease chemistry Ventromedial hypothalamic nucleus Catecholamine biology.protein medicine.drug |
| Zdroj: | Endocrine and Metabolic Science, Vol 3, Iss, Pp 100087-(2021) Endocrine and metabolic science |
| ISSN: | 2666-3961 |
| DOI: | 10.1016/j.endmts.2021.100087 |
| Popis: | Ventromedial hypothalamic nucleus (VMN) glycogen metabolism affects local glucoregulatory signaling. The hindbrain metabolic-sensitive catecholamine (CA) neurotransmitter norepinephrine controls VMN glycogen phosphorylase (GP)-muscle (GPmm) and -brain (GPbb) type expression in male rats. Present studies addressed the premise that CA regulation of hypoglycemic patterns of VMN glycogen metabolic enzyme protein expression is sex-dimorphic, and that this signal is responsible for sex differences in acclimation of these profiles to recurrent insulin-induced hypoglycemia (RIIH). VMN tissue was acquired by micropunch-dissection from male and female rats pretreated by caudal fourth ventricular administration of the CA neurotoxin 6-hydroxydopamine (6OHDA) before single or serial insulin injection. 6-OHDA averted acute hypoglycemic inhibition of VMN glycogen synthase (GS) and augmentation of GPmm and GPbb protein expression in males, and prevented GPmm and -bb down-regulation in females. Males recovered from antecedent hypoglycemia (AH) exhibited neurotoxin-preventable diminution of baseline GS profiles, whereas acclimated GPmm and -bb expression in females occurred irrespective of pretreatment. RIIH did not alter VMN GS, GPmm, and GPbb expression in vehicle- or 6-OHDA-pretreated animals of either sex. VMN glycogen content was correspondingly unchanged or increased in males versus females following AH; 6-OHDA augmented glycogen mass in AH-exposed animals of both sexes. RIIH did not alter VMN glycogen accumulation in vehicle-pretreated rats of either sex, but diminished glycogen in neurotoxin-pretreated animals. AH suppresses baseline GS (CA-dependent) or GPmm/GPbb (CA-independent) expression in male and female rats, respectively, which corresponds with unaltered or augmented VMN glycogen content in those sexes. AH-associated loss of sex-distinctive CA-mediated enzyme protein sensitivity to hypoglycemia (male: GS, GPmm, GPbb; female: GPmm, Gpbb) may reflect, in part, VMN target desensitization to noradrenergic input. |
| Databáze: | OpenAIRE |
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