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Liver glycogen loading dampens glycogen synthesis seen in response to either hyperinsulinemia or intraportal glucose infusion.

Winnick JJ, An Z, Kraft G, Ramnanan CJ, Irimia JM, Smith M, Lautz M, Roach PJ, Cherrington AD - Diabetes (2012)

Bottom Line: Increased hepatic glycogen reduced the percent of glucose taken up by the liver that was deposited in glycogen (74 ± 3 vs. 53 ± 5% in Gly+INS and SCGly+INS, respectively, and 72 ± 3 vs. 50 ± 6% in Gly+PoG and SCGly+PoG, respectively).The reduction in liver glycogen synthesis in SCGly+INS was accompanied by a decrease in both insulin signaling and an increase in AMPK activation, whereas only the latter was observed in SCGly+PoG.These data indicate that liver glycogen loading impairs glycogen synthesis regardless of the signal used to stimulate it.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. jason.winnick@vanderbilt.edu

ABSTRACT
The purpose of this study was to determine the effect of liver glycogen loading on net hepatic glycogen synthesis during hyperinsulinemia or hepatic portal vein glucose infusion in vivo. Liver glycogen levels were supercompensated (SCGly) in two groups (using intraportal fructose infusion) but not in two others (Gly) during hyperglycemic-normoinsulinemia. Following a 2-h control period during which fructose infusion was stopped, there was a 2-h experimental period in which the response to hyperglycemia plus either 4× basal insulin (INS) or portal vein glucose infusion (PoG) was measured. Increased hepatic glycogen reduced the percent of glucose taken up by the liver that was deposited in glycogen (74 ± 3 vs. 53 ± 5% in Gly+INS and SCGly+INS, respectively, and 72 ± 3 vs. 50 ± 6% in Gly+PoG and SCGly+PoG, respectively). The reduction in liver glycogen synthesis in SCGly+INS was accompanied by a decrease in both insulin signaling and an increase in AMPK activation, whereas only the latter was observed in SCGly+PoG. These data indicate that liver glycogen loading impairs glycogen synthesis regardless of the signal used to stimulate it.

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NHGU (A), net glycogen synthesis (B), net hepatic lactate output (NHLO) (C), and hepatic glucose oxidation (D) during the experimental period.
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Figure 2: NHGU (A), net glycogen synthesis (B), net hepatic lactate output (NHLO) (C), and hepatic glucose oxidation (D) during the experimental period.

Mentions: During both the control and experimental periods, the arterial blood glucose level and the glucose load to the liver were not different among groups (Fig. 1). At the outset of the experimental period (i.e., min 0), the hepatic sinusoidal insulin concentration was raised fourfold in the Gly+INS and SCGly+INS groups and maintained at a basal value in Gly+PoG and SCGly+PoG (Fig. 1C). In all four groups, the hepatic sinusoidal glucagon levels remained basal throughout the study (Fig. 1D). NHGU was modest during the final 30 min of the control period in all groups (Fig. 2A) and increased along with net glycogen synthesis in all groups over the 2-h test period (Fig. 2B). Nevertheless, the area under the curve for glycogen synthesis over the final hour of the experimental period was lower in SCGly+INS and SCGly+PoG than in their respective saline-infused groups (P < 0.05). The reduction in net glycogen synthesis was primarily accounted for by increased hepatic lactate output (Fig. 2C; P < 0.05). When expressed as a percentage of NHGU, glycogen synthesis was reduced in both SCGly groups compared with their respective saline-infused controls, whereas lactate output was increased (Fig. 3; P < 0.05).


Liver glycogen loading dampens glycogen synthesis seen in response to either hyperinsulinemia or intraportal glucose infusion.

Winnick JJ, An Z, Kraft G, Ramnanan CJ, Irimia JM, Smith M, Lautz M, Roach PJ, Cherrington AD - Diabetes (2012)

NHGU (A), net glycogen synthesis (B), net hepatic lactate output (NHLO) (C), and hepatic glucose oxidation (D) during the experimental period.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3526057&req=5

Figure 2: NHGU (A), net glycogen synthesis (B), net hepatic lactate output (NHLO) (C), and hepatic glucose oxidation (D) during the experimental period.
Mentions: During both the control and experimental periods, the arterial blood glucose level and the glucose load to the liver were not different among groups (Fig. 1). At the outset of the experimental period (i.e., min 0), the hepatic sinusoidal insulin concentration was raised fourfold in the Gly+INS and SCGly+INS groups and maintained at a basal value in Gly+PoG and SCGly+PoG (Fig. 1C). In all four groups, the hepatic sinusoidal glucagon levels remained basal throughout the study (Fig. 1D). NHGU was modest during the final 30 min of the control period in all groups (Fig. 2A) and increased along with net glycogen synthesis in all groups over the 2-h test period (Fig. 2B). Nevertheless, the area under the curve for glycogen synthesis over the final hour of the experimental period was lower in SCGly+INS and SCGly+PoG than in their respective saline-infused groups (P < 0.05). The reduction in net glycogen synthesis was primarily accounted for by increased hepatic lactate output (Fig. 2C; P < 0.05). When expressed as a percentage of NHGU, glycogen synthesis was reduced in both SCGly groups compared with their respective saline-infused controls, whereas lactate output was increased (Fig. 3; P < 0.05).

Bottom Line: Increased hepatic glycogen reduced the percent of glucose taken up by the liver that was deposited in glycogen (74 ± 3 vs. 53 ± 5% in Gly+INS and SCGly+INS, respectively, and 72 ± 3 vs. 50 ± 6% in Gly+PoG and SCGly+PoG, respectively).The reduction in liver glycogen synthesis in SCGly+INS was accompanied by a decrease in both insulin signaling and an increase in AMPK activation, whereas only the latter was observed in SCGly+PoG.These data indicate that liver glycogen loading impairs glycogen synthesis regardless of the signal used to stimulate it.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. jason.winnick@vanderbilt.edu

ABSTRACT
The purpose of this study was to determine the effect of liver glycogen loading on net hepatic glycogen synthesis during hyperinsulinemia or hepatic portal vein glucose infusion in vivo. Liver glycogen levels were supercompensated (SCGly) in two groups (using intraportal fructose infusion) but not in two others (Gly) during hyperglycemic-normoinsulinemia. Following a 2-h control period during which fructose infusion was stopped, there was a 2-h experimental period in which the response to hyperglycemia plus either 4× basal insulin (INS) or portal vein glucose infusion (PoG) was measured. Increased hepatic glycogen reduced the percent of glucose taken up by the liver that was deposited in glycogen (74 ± 3 vs. 53 ± 5% in Gly+INS and SCGly+INS, respectively, and 72 ± 3 vs. 50 ± 6% in Gly+PoG and SCGly+PoG, respectively). The reduction in liver glycogen synthesis in SCGly+INS was accompanied by a decrease in both insulin signaling and an increase in AMPK activation, whereas only the latter was observed in SCGly+PoG. These data indicate that liver glycogen loading impairs glycogen synthesis regardless of the signal used to stimulate it.

Show MeSH
Related in: MedlinePlus