title: Norepinephrine and epinephrine-deficient mice are hyperinsulinemic and have lower blood glucose.
abstract: Norepinephrine (NE) and epinephrine (Epi) help maintain normal blood glucose levels by stimulating glucagon release, glycogenolysis, and food consumption, and by inhibiting insulin release. The absence of NE and Epi in dopamine beta-hydroxylase-null (Dbh-/-) mice results in chronically low blood glucose levels, an impaired glucagon response to hypoglycemia, and elevated insulin levels. Nevertheless, Dbh-/- mice have normal glycogen levels and degrade it normally during a fast. Dbh-/- mice defend blood glucose levels better than controls in an insulin tolerance test but have increased sensitivity to glucose-stimulated insulin secretion and respond normally in a glucose tolerance test. Pharmacological evidence indicates that the hyperinsulinemia results from lack of alpha2-adrenoreceptor stimulation and increased parasympathetic tone. Dbh-/- mice eat normally after challenges with modest levels of insulin or 2-deoxyglucose but fail to eat under more extreme conditions when control mice still do. We suggest that the primary difference in Dbh-/- mice is chronic hyperinsulinemia associated with an altered glucose set point. However, these animals compensate for NE/Epi-mediated glycogenolysis and feeding.
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Ste Marie
authors.forename: Richard D
authors.initials: RD
authors.lastname: Palmiter
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001286:Atropine Derivatives / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D004435:Eating / Q000187:drug effects; D004837:Epinephrine / Q000172:deficiency / Q000502:physiology*; D005260:Female; D005934:Glucagon / Q000378:metabolism; D005951:Glucose Tolerance Test; D006003:Glycogen / Q000378:metabolism; D006946:Hyperinsulinism / Q000097:blood / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009638:Norepinephrine / Q000172:deficiency / Q000502:physiology*
chemical_list: D000316:Adrenergic alpha-Agonists; D001286:Atropine Derivatives; D001786:Blood Glucose; D007328:Insulin; D018727:Muscarinic Antagonists; C006649:methylatropine; D006003:Glycogen; D005934:Glucagon; D003847:Deoxyglucose; D003000:Clonidine; D009638:Norepinephrine; D004837:Epinephrine