title: Prevention of overt hypoglycemia during exercise: stimulation of endogenous glucose production independent of hepatic catecholamine action and changes in pancreatic hormone concentration.
abstract: These studies were conducted to determine the magnitude and mechanism of compensation for impaired glucagon and insulin responses to exercise. For this purpose, dogs underwent surgery >16 days before experiments, at which time flow probes were implanted and silastic catheters were inserted. During experiments, glucagon and insulin were fixed at basal levels during rest and exercise using a pancreatic clamp with glucose clamped (PC/GC; n = 5), a pancreatic clamp with glucose unclamped (PC; n = 7), or a pancreatic clamp with glucose unclamped + intraportal propranolol and phentolamine hepatic alpha- and beta-adrenergic receptor blockade (PC/HAB; n = 6). Glucose production (R(a)) was measured isotopically. Plasma glucose was constant in PC/GC, but fell from basal to exercise in PC and PC/HAB. R(a) was unchanged with exercise in PC/GC, but was slightly increased during exercise in PC and PC/HAB. Despite minimal increases in epinephrine in PC/GC, epinephrine increased approximately sixfold in PC and PC/HAB during exercise. In summary, during moderate exercise, 1) the increase in R(a) is absent in PC/GC; 2) only a moderate fall in arterial glucose occurs in PC, due to a compensatory increase in R(a); and 3) the increase in R(a) is preserved in PC/HAB. In conclusion, stimulation of R(a) by a mechanism independent of pancreatic hormones and hepatic adrenergic stimulation is a primary defense against overt hypoglycemia.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. cokerrobert@uams.edu
authors.forename: Robert H
authors.initials: RH
authors.lastname: Coker
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Koyama
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Denny
authors.forename: Raul C
authors.initials: RC
authors.lastname: Camacho
authors.forename: D Brooks
authors.initials: DB
authors.lastname: Lacy
authors.forename: David H
authors.initials: DH
authors.lastname: Wasserman
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000409:Alanine / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000096:biosynthesis*; D004285:Dogs; D004837:Epinephrine / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood; D015309:Glucose Clamp Technique; D005990:Glycerol / Q000097:blood; D006339:Heart Rate; D007003:Hypoglycemia / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D007328:Insulin / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D008099:Liver / Q000378:metabolism; D008102:Liver Circulation; D009638:Norepinephrine / Q000097:blood*; D005082:Physical Exertion / Q000502:physiology*
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D019344:Lactic Acid; D005934:Glucagon; D000409:Alanine; D005990:Glycerol; D009638:Norepinephrine; D004837:Epinephrine