Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Aug;297(2):E358-66.
doi: 10.1152/ajpendo.00043.2009. Epub 2009 May 26.

A physiological increase in the hepatic glycogen level does not affect the response of net hepatic glucose uptake to insulin

Jason J Winnick  1 , Zhibo An, Mary Courtney Moore, Christopher J Ramnanan, Ben Farmer, Masakazu Shiota, Alan D Cherrington
Affiliations

A physiological increase in the hepatic glycogen level does not affect the response of net hepatic glucose uptake to insulin

Jason J Winnick et al. Am J Physiol Endocrinol Metab. 2009 Aug.

Abstract

To determine the effect of an acute increase in hepatic glycogen on net hepatic glucose uptake (NHGU) and disposition in response to insulin in vivo, studies were performed on two groups of dogs fasted 18 h. During the first 4 h of the study, somatostatin was infused peripherally, while insulin and glucagon were replaced intraportally in basal amounts. Hyperglycemia was brought about by glucose infusion, and either saline (n = 7) or fructose (n = 7; to stimulate NHGU and glycogen deposition) was infused intraportally. A 2-h control period then followed, during which the portal fructose and saline infusions were stopped, allowing NHGU and glycogen deposition in the fructose-infused animals to return to rates similar to those of the animals that received the saline infusion. This was followed by a 2-h experimental period, during which hyperglycemia was continued but insulin infusion was increased fourfold in both groups. During the initial 4-h glycogen loading period, NHGU averaged 1.18 +/- 0.27 and 5.55 +/- 0.53 mg x kg(-1) x min(-1) and glycogen synthesis averaged 0.72 +/- 0.24 and 3.98 +/- 0.57 mg x kg(-1) x min(-1) in the saline and fructose groups, respectively (P < 0.05). During the 2-h hyperinsulinemic period, NHGU rose from 1.5 +/- 0.4 and 0.9 +/- 0.2 to 3.1 +/- 0.6 and 2.5 +/- 0.5 mg x kg(-1) x min(-1) in the saline and fructose groups, respectively, a change of 1.6 mg x kg(-1) x min(-1) in both groups despite a significantly greater liver glycogen level in the fructose-infused group. Likewise, the metabolic fate of the extracted glucose (glycogen, lactate, or carbon dioxide) was not different between groups. These data indicate that an acute physiological increase in the hepatic glycogen content does not alter liver glucose uptake and storage under hyperglycemic/hyperinsulinemic conditions in the dog.

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.
Schematic representation of the study. SRIF, somatostatin.
Fig. 2.
Fig. 2.
Arterial blood glucose (A), hepatic sinusoidal insulin (B), hepatic sinusoidal glucagon (C), net hepatic glucose uptake (NHGU; D), net hepatic glycogen synthesis (E), and net hepatic lactate output (NHLO, in glucose equivalents; F) during the final 20 min of the 4-h glycogen loading period. *P < 0.05, fructose infusion group compared with saline infusion group.
Fig. 3.
Fig. 3.
Arterial blood glucose (A), glucose load to the liver (B), hepatic sinusoidal insulin (C), and hepatic sinusoidal glucagon (D) before and during the experimental period. No differences were detected between groups for any variable [P = not significant (NS)].
Fig. 4.
Fig. 4.
NHGU (A), net hepatic glycogen synthesis (B), NHLO (in glucose equivalents; C), and hepatic glucose oxidation (D) during the experimental period. No differences were detected between groups at any time point (P = NS). * and #Significantly different (P < 0.05) from minute 0 in saline and fructose groups, respectively.
Fig. 5.
Fig. 5.
Relationship between the terminal liver glycogen level and terminal NHGU (r = 0.16, P = NS; A) and the relationship between NHGU and net glycogen synthesis during the final hour of the experimental period (r = 0.93; P < 0.001; B).
Fig. 6.
Fig. 6.
Postexperimental hepatic Akt (A) and GSK3β (B) signaling. Top: Western blot data representative of all animals (S and F, saline- and fructose-infused animals, respectively). No difference was observed between groups for either measure (P = NS).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Adkins-Marshall BA, Myers SR, Hendrick GK, Williams PE, Triebwasser K, Floyd B, Cherrington AD. Interaction between insulin and glucose-delivery route in regulation of net hepatic glucose uptake in conscious dogs. Diabetes 39: 87–95, 1990. - PubMed
    1. Agius L, Peak M. Intracellular binding of glucokinase in hepatocytes and translocation by glucose, fructose and insulin. Biochem J 296: 785–796, 1993. - PMC - PubMed
    1. Basu A, Basu R, Shah P, Vella A, Johnson CM, Jensen M, Nair KS, Schwenk WF, Rizza RA. Type 2 diabetes impairs splanchnic uptake of glucose but does not alter intestinal glucose absorption during enteral glucose feeding: additional evidence for a defect in hepatic glucokinase activity. Diabetes 50: 1351–1362, 2001. - PubMed
    1. Basu A, Basu R, Shah P, Vella A, Johnson CM, Nair KS, Jensen MD, Schwenk WF, Rizza RA. Effects of type 2 diabetes on the ability of insulin and glucose to regulate splanchnic and muscle glucose metabolism: evidence for a defect in hepatic glucokinase activity. Diabetes 49: 272–283, 2000. - PubMed
    1. Basu R, Basu A, Johnson CM, Schwenk WF, Rizza RA. Insulin dose-response curves for stimulation of splanchnic glucose uptake and suppression of endogenous glucose production differ in nondiabetic humans and are abnormal in people with type 2 diabetes. Diabetes 53: 2042–2050, 2004. - PubMed

Publication types

MeSH terms

  NODES
twitter 2