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Am J Physiol Endocrinol Metab (October 10, 2001). doi:10.1152/ajpendo.00136.2001
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Articles in PresS, published online ahead of print October 10, 2001
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00136.2001
Submitted on March 20, 2001
Accepted on September 17, 2001

The Effects of Free Fatty Acids on Hepatic Glycogenolysis and Gluconeogenesis In the Conscious Dog

Chang A Chu1, Stephanie M Sherck1, Kayano Igawa1, Dana K Sindelar1, Doss W Neal1, Maya Emshwiller1, and Alan D Cherrington1*

1 Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA

* To whom correspondence should be addressed. E-mail: alan.cherrington{at}mcmail.vanderbilt.edu.

The aim of this study was to determine the effect of high levels of free fatty acids (FFA) and/or hyperglycemia on hepatic glycogenolysis and gluconeogenesis. Intralipid was infused peripherally into 18h-fasted conscious dogs maintained on a pancreatic clamp in the presence (FFA+HG, n=6) or absence (FFA+EuG, n=6) of hyperglycemia. In the control studies, Intralipid was not infused and euglycemia (EuG, n = 6) or hyperglycemia (HG, n=6) were maintained. Insulin and glucagon were clamped at basal levels in all four groups. The arterial blood glucose level increased by 50% in the HG and FFA+HG groups. It did not change in the EuG and FFA+EuG groups. Arterial plasma free fatty acids increased by ~140% in the FFA+EuG and FFA+HG groups, but did not change significantly either in the EuG or HG groups. Arterial glycerol levels increased by ~150% in both groups. Overall (3h) hepatic glycogenolysis was 196 ± 26 mg/kg in the EuG group. It decreased by 96 ± 20, 82 ± 16, and 177 ± 22 mg/kg in the HG, FFA+EuG, and FFA+HG groups, respectively. Overall (3h) hepatic gluconeogenesis was 128 ± 22 mg/kg in the EuG group but it was suppressed by 30 ± 9 mg/kg in response to hyperglycemia. It was increased by 59 ± 12 and 56 ± 10 mg/kg in the FFA+EuG and FFA+HG groups, respectively. In summary, 1) an increase in plasma free fatty acids and glycerol significantly inhibited hepatic glycogenolysis and markedly stimulated hepatic gluconeogenesis. 2) Hyperglycemia, on the other hand, significantly inhibited hepatic glycogenolysis, but only modestly decreased gluconeogenesis. 3) Free fatty acids, glycerol and hyperglycemia had an additive effect in inhibiting hepatic glycogenolysis, 4) FFA and glycerol overcame the inhibitory effect of hyperglycemia on gluconeogenesis




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