التفاصيل البيبلوغرافية
| العنوان: |
Hepatic Glycogen Supercompensation Activates AMP-Activated Protein Kinase, Impairs Insulin Signaling, and Reduces Glycogen Deposition in the Liver. |
| المؤلفون: |
Winnick, Jason J., An, Zhibo, Ramnanan, Christopher J., Smith, Marta, Irimia, Jose M., Neal, Doss W., Moore, Mary Courtney, Roach, Peter J., Cherrington, Alan D. |
| المصدر: |
Diabetes; Feb2011, Vol. 60 Issue 2, p398-407, 10p, 1 Diagram, 1 Chart, 5 Graphs |
| مصطلحات موضوعية: |
GLYCOGEN, LIVER, GLUCOSE, FRUCTOSE, HYPERGLYCEMIA, INSULIN shock, LACTATES, PHOSPHORYLATION |
| مستخلص: |
OBJECTIVE--The objective of this study was to determine how increasing the hepatic glycogen content would affect the liver's ability to take up and metabolize glucose. RESEARCH DESIGN AND METHODS--During the first 4 h of the study, liver glycogen deposition was stimulated by intraportal fructose infusion in the presence of hyperglycemic-normoinsuline-mia. This was followed by a 2-h hyperglycemic-normoinsulinemic control period, during which the fructose infusion was stopped, and a 2-h experimental period in which net hepatic glucose uptake (NHGU) and disposition (glycogen, lactate, and C02) were measured in the absence of fructose but in the presence of a hyperglycemic-hyperinsulinemic challenge including portal vein glucose infusion. RESULTS--Fructose infusion increased net hepatic glycogen synthesis (0.7 ± 0.5 vs. 6.4 ± 0.4 mg/kg/min; P < 0.001), causing a large difference in hepatic glycogen content (62 ± 9 vs. 100 ± 3 mg/g; P < 0.001). Hepatic glycogen supercompensation (fructose infusion group) did not alter NHGU, but it reduced the percent of NHGU directed to glycogen (79 ± 4 vs. 55 ± 6; P < 0.01) and increased the percent directed to lactate (12 ± 3 vs. 29 ± 5; P = 0.01) and oxidation (9 ± 3 vs. 16 ± 3; P = NS). This change was associated with increased AMP-activated protein kinase phosphorylation, diminished insulin signaling, and a shift in glycogenic enzyme activity toward a state discouraging glycogen accumulation. CONCLUSIONS--These data indicate that increases in hepatic glycogen can generate a state of hepatic insulin resistance, which is characterized by impaired glycogen synthesis despite preserved NHGU. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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