title: Efficiency of compensation for absence of fall in insulin during exercise.
abstract: To assess compensation for the absence of the exercise-induced fall in insulin, dogs underwent 150 min of treadmill exercise with insulin infused intraportally with (IC + Glc; n = 7) or without (IC; n = 6) glucose clamped. Glucose production (Ra), gluconeogenic conversion (Conv), and intrahepatic gluconeogenic efficiency (Eff) were assessed with tracers ([3H]glucose, [14C]alanine) and arteriovenous differences. Glucose fell by 6 +/- 4 and 11 +/- 2 mg/dl at 30 min of exercise and by 8 +/- 2 and 36 +/- 5 mg/dl at 150 min in IC + Glc and IC. Glucagon rose by 16 +/- 8 and 55 +/- 17 pg/ml by 30 min of exercise and by 18 +/- 6 and 93 +/- 22 pg/ml by 150 min in IC + Glc and IC. Norepinephrine was unaffected by the glycemic decrement in IC, whereas epinephrine was greater for the last 60 min of exercise. Ra rose by an average of 0.9 +/- 0.3 and 3.7 +/- 0.2 mg.kg-1.min-1 in IC + Glc and IC. Conv rose by 91 +/- 39 and 325 +/- 75% in IC + Glc and IC at 150 min of exercise, and Eff rose by 87 +/- 57 and 358 +/- 99%. The compensatory Ra exceeded the maximum possible gluconeogenic rate, indicating that glycogenolysis was also stimulated. In summary, in the absence of the exercise-induced fall in insulin 1) glycemia falls approximately fourfold faster; 2) minimal glycemic decrements elicit a large and rapid increase in Ra; 3) this compensation involves a glycogenolytic and gluconeogenic response; 4) the accelerated gluconeogenic rate is due, in large part, to stimulation of Eff; and 5) the compensatory Ra is likely mediated, in part, by glucagon. Hence, although the fall in insulin is essential for normal glucoregulation during exercise, a highly sensitive counterregulatory response prevents severe hypoglycemia. The remarkable sensitivity of the liver to small changes in glycemia implies that the normal coupling of the exercise-induced increase in Ra to glucose utilization may be signaled by small, nearly imperceptible changes in glucose.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
authors.forename: D H
authors.initials: DH
authors.lastname: Wasserman
authors.forename: D B
authors.initials: DB
authors.lastname: Lacy
authors.forename: C A
authors.initials: CA
authors.lastname: Colburn
authors.forename: D
authors.initials: D
authors.lastname: Bracy
authors.forename: A D
authors.initials: AD
authors.lastname: Cherrington
mesh_terms: D000222:Adaptation, Physiological; D000409:Alanine / Q000378:metabolism; D000818:Animals; D001158:Arteries; D002395:Catecholamines / Q000097:blood; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood; D005943:Gluconeogenesis; D005990:Glycerol / Q000378:metabolism; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood*; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000378:metabolism; D005082:Physical Exertion / Q000502:physiology*
chemical_list: D002395:Catecholamines; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007773:Lactates; D019344:Lactic Acid; D005934:Glucagon; D000409:Alanine; D005990:Glycerol; D006854:Hydrocortisone