The effect of an acute elevation of NEFA concentrations on glucagon-stimulated hepatic glucose output.
To determine the effect of nonesterified fatty acids (NEFA) on glucagon action, glucagon was infused intraportally (1.65 ng.min(-1).kg(-1)) for 3 h into 18-h-fasted, pancreatic-clamped conscious dogs in the presence [NEFA + glucagon (GGN)] or absence (GGN) of peripheral Intralipid plus heparin infusion. Additionally, hyperglycemic (HG), hyperglycemic-hyperlipidemic (NEFA + HG), and glycerol plus glucagon (GLYC + GGN) controls were studied. Arterial plasma glucagon concentrations rose equally in GGN, NEFA + GGN, and GLYC + GGN but remained basal in hyperglycemic controls. Peripheral infusions of Intralipid and heparin increased arterial plasma NEFA concentrations equally in NEFA + GGN and NEFA + HG and did not change in other protocols. After 15 min, glucagon infusion resulted in a rapid, brief increase in net hepatic glycogenolysis (NHGLY, mg.min(-1).kg(-1)) of approximately 6.0 in GGN and GLYC + GGN but only increased by 3.8 +/- 1.3 in NEFA + GGN. Thus increases in NHGLY, and consequently net hepatic glucose output (NHGO), were blunted by 40%, with no difference between the groups in the last 2.5 h of the study. NHGO and NHGLY did not significantly change in HG and NEFA + HG. Net hepatic gluconeogenic flux did not change in GGN, GLYC + GGN, or HG. However, Intralipid and heparin infusion resulted in similar increases in net hepatic gluconeogenic flux in NEFA + GGN and NEFA + HG. Thus elevated NEFA limit the initial increase in glucagon-stimulated HGO by blunting glycogenolysis, without having any effect on the gluconeogenic or glycogenolytic contributions or NHGO thereafter.
Everett-Grueter
Carrie
C
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA. carrie.everett@vanderbilt.edu
Edgerton
Dale S
DS
Donahue
E Patrick
EP
Vaughan
Suzan
S
Chu
Chang An
CA
Sindelar
Dana K
DK
Cherrington
Alan D
AD
D020155:3-Hydroxybutyric Acid / Q000097:blood / Q000378:metabolism; D000090:Acetoacetates / Q000097:blood / Q000378:metabolism; D000596:Amino Acids / Q000097:blood / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D005934:Glucagon / Q000097:blood / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D015309:Glucose Clamp Technique; D005990:Glycerol / Q000097:blood / Q000494:pharmacology; D050261:Glycogenolysis / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology; D006943:Hyperglycemia / Q000097:blood / Q000378:metabolism; D007328:Insulin / Q000097:blood; D019344:Lactic Acid / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*
D000090:Acetoacetates; D000596:Amino Acids; D001786:Blood Glucose; D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D019344:Lactic Acid; C016635:acetoacetic acid; D006493:Heparin; D005934:Glucagon; D000242:Cyclic AMP; D005947:Glucose; D005990:Glycerol; D020155:3-Hydroxybutyric Acid