The effect of an acute elevation of NEFA concentrations on glucagon-stimulated hepatic glucose output.

Everett-Grueter C, Edgerton DS, Donahue EP, Vaughan S, Chu CA, Sindelar DK, Cherrington AD
Am J Physiol Endocrinol Metab. 2006 291 (3): E449-59

PMID: 16608886 · DOI:10.1152/ajpendo.00043.2006

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.

MeSH Terms (20)

3-Hydroxybutyric Acid Acetoacetates Amino Acids Animals Blood Glucose Cyclic AMP Dogs Fat Emulsions, Intravenous Fatty Acids, Nonesterified Glucagon Gluconeogenesis Glucose Glucose Clamp Technique Glycerol Glycogenolysis Heparin Hyperglycemia Insulin Lactic Acid Liver

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