title: Local lactate perfusion of the ventromedial hypothalamus suppresses hypoglycemic counterregulation.
abstract: We have previously reported that a glucosensor integrating hormonal responses to hypoglycemia is located in the ventromedial hypothalamus (VMH) and that local VMH glucose perfusion blocks counterregulatory hormone responses. To determine whether the by-product of glucose metabolism, lactate, can function within the VMH as an alternative for glucose, we delivered lactate locally to the VMH, during systemic hypoglycemia. For this purpose, we combined bilateral VMH microdialysis perfusion (metabolically active L-lactate or its nonmetabolizable D-isomer) with a euglycemic-hypoglycemic clamp in conscious chronically catheterized Sprague-Dawley rats. Local VMH perfusion with L-lactate decreased counterregulatory hormone responses to hypoglycemia by 80-85% as compared with the nonmetabolizable D-lactate control. Moreover, hormonal suppression with L-lactate was accompanied by an approximate fourfold increase in the amount of exogenous glucose infused to maintain a stable hypoglycemic plateau (P < 0.05). In conclusion, the glucose-sensing mechanism in the VMH responds to lactate and, thus, is not specific for glucose. This implies that the VMH may act as a fuel sensor rather than as a glucose sensor.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8020, USA.
authors.forename: Monica A
authors.initials: MA
authors.lastname: Borg
authors.forename: William V
authors.initials: WV
authors.lastname: Tamborlane
authors.forename: Gerald I
authors.initials: GI
authors.lastname: Shulman
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sherwin
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004837:Epinephrine / Q000097:blood; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000008:administration & dosage; D006706:Homeostasis; D007003:Hypoglycemia / Q000503:physiopathology*; D007033:Hypothalamus, Middle / Q000187:drug effects* / Q000503:physiopathology; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D007700:Kinetics; D019344:Lactic Acid / Q000008:administration & dosage*; D008297:Male; D017551:Microdialysis; D009638:Norepinephrine / Q000097:blood; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D007328:Insulin; D019344:Lactic Acid; D005934:Glucagon; D005947:Glucose; D009638:Norepinephrine; D004837:Epinephrine