| Autor: |
Hussain N. Alhamami, Ayed Alshamrani, Karen P. Briski |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
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| Zdroj: |
Physiological Reports, Vol 5, Iss 23, Pp n/a-n/a (2017) |
| Druh dokumentu: |
article |
| ISSN: |
2051-817X |
| DOI: |
10.14814/phy2.13484 |
| Popis: |
Abstract The glucose polymer glycogen is a vital fuel reserve in the brain. The mediobasal hypothalamic energy sensor AMP‐activated protein kinase (AMPK) maintains glucostasis via neurotransmitter mechanisms that suppress [γ‐aminobutyric acid; GABA] or stimulate [nitric oxide; steroidogenic factor‐1 (SF1)] counter‐regulatory outflow. This study investigated whether glycogen‐derived fuel supply is a critical screened variable in ventromedial hypothalamic nucleus (VMN) monitoring of neuro‐metabolic stability during glucostasis and/or insulin (I)‐induced hypoglycemia. Adult male rats were pretreated by intra‐VMN infusion of the glycogen phosphorylase inhibitor 1,4‐dideoxy‐1,4‐imino‐D‐arabinitol (DAB) before sc vehicle or I injection. Western blot analyses of micropunch‐dissected VMN tissue from euglycemic animals showed DAB augmentation of phosphoAMPK (pAMPK), neuronal nitric oxide synthase (nNOS), and SF‐1, but not glutamate decarboxylase65/67 (GAD) protein. Combinatory DAB/I treatment did not further enhance AMPK activity but significantly amplified nNOS expression relative to DAB alone. Hypoglycemic stimulation of corticosterone, but not glucagon release was prevented by DAB. Results imply that glycogen‐derived substrate fuel provision represses VMN AMPK activity and neurotransmitter signals of metabolic deficiency. Progressive augmentation of nNOS protein by DAB/I versus DAB/V intimates that “fuel‐inhibited” nitrergic neurons may exhibit increasing sensitivity to disrupted glycogen breakdown during glucoprivation versus glucostasis. nNOS and GAD reactivity to DAB/I, but not I implies that acute glycogen utilization during hypoglycemia may be sufficiently robust to avert effects on local metabolic sensory signaling. DAB/I upregulation of GAD alongside prevention of hypercorticosteronemia suggests that indicators of metabolic sufficiency may occur secondary to local compensatory adaptations to severe restriction of glucose‐derived energy. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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