Open AccessInhibition of glycogen phosphorylase stimulates ventromedial hypothalamic nucleus AMP ‐activated protein kinase
Author(s) -
Alhamami Hussain N.,
Alshamrani Ayed,
Briski Karen P.
Publication year - 2017
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13484
Subject(s) - medicine , endocrinology , ampk , glycogen , glycogen phosphorylase , amp activated protein kinase , glycogen synthase , chemistry , protein kinase a , glutamate receptor , nitric oxide synthase , biology , kinase , nitric oxide , receptor , biochemistry
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 ( SF 1)] 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 phospho AMPK ( pAMPK ), neuronal nitric oxide synthase ( nNOS ), and SF ‐1, but not glutamate decarboxylase 65/67 ( 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.