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Review
. 2012 May 1;3(3):286-94.
doi: 10.3945/an.112.002089.

Regulation of hepatic glucose uptake and storage in vivo

Mary Courtney Moore  1 , Katie C Coate, Jason J Winnick, Zhibo An, Alan D Cherrington
Affiliations
Review

Regulation of hepatic glucose uptake and storage in vivo

Mary Courtney Moore et al. Adv Nutr. .

Abstract

In the postprandial state, the liver takes up and stores glucose to minimize the fluctuation of glycemia. Elevated insulin concentrations, an increase in the load of glucose reaching the liver, and the oral/enteral/portal vein route of glucose delivery (compared with the peripheral intravenous route) are factors that increase the rate of net hepatic glucose uptake (NHGU). The entry of glucose into the portal vein stimulates a portal glucose signal that not only enhances NHGU but concomitantly reduces muscle glucose uptake to ensure appropriate partitioning of a glucose load. This coordinated regulation of glucose uptake is likely neurally mediated, at least in part, because it is not observed after total hepatic denervation. Moreover, there is evidence that both the sympathetic and the nitrergic innervation of the liver exert a tonic repression of NHGU that is relieved under feeding conditions. Further, the energy sensor 5'AMP-activated protein kinase appears to be involved in regulation of NHGU and glycogen storage. Consumption of a high-fat and high-fructose diet impairs NHGU and glycogen storage in association with a reduction in glucokinase protein and activity. An understanding of the impact of nutrients themselves and the route of nutrient delivery on liver carbohydrate metabolism is fundamental to the development of therapies for impaired postprandial glucoregulation.

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Conflict of interest statement

Author disclosures. M.C. Moore, K.C. Coate, J.J. Winnick, Z. An, and A.D. Cherrington, no conflicts of interest.

Figures

Figure 1
Figure 1
Distribution of a glucose load among the liver, insulin-sensitive tissues, and noninsulin-sensitive tissues. CNS, central nervous system; RBC, red blood cell. Reproduced from Reference with permission.
Figure 2
Figure 2
Factors affecting the magnitude of net hepatic glucose uptake (NHGU). In the physiologic range, increases in the amount of insulin reaching the liver and the hepatic glucose load stimulate NHGU. When the insulin concentrations and hepatic glucose loads are equivalent with the 2 routes of delivery, NHGU is approximately 2-fold greater when glucose is delivered via the portal versus a peripheral vein.
Figure 3
Figure 3
The relationship of nitric oxide (NO) and net hepatic glucose uptake (NHGU). In the presence of the portal glucose signal, increasing hepatic NO by intraportal infusion of 3-morpholinosydnominine HCl (A) or mimicking NO activation of the soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway by infusing the cGMP analogue 8-Br-cGMP intraportally (B) blunted NHGU. On the other hand, in the absence of the portal glucose signal, reducing hepatic NO by intraportal infusion of the NO synthase inhibitor Nω-nitro-l-arginine methyl ester (C) or blocking the activation of the sGC/cGMP pathway with the sGC inhibitor 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (D) enhanced NHGU. *P < 0.05 vs. vehicle. Data from References (52, 53, 80, 81).
Figure 4
Figure 4
The distribution of a glucose load between the liver and insulin-sensitive tissues (primarily skeletal muscle) is finely controlled. Ingestion of glucose or infusion of glucose into the portal vein creates a negative arterial-portal glucose gradient (portal vein concentration higher than that in the artery) that is sensed within the liver, giving rise to the portal glucose signal, which is associated with an increase in net hepatic glucose uptake (NHGU) coupled with a decrease in muscle glucose uptake. Afferent signals regarding hepatoportal glucose levels can be transmitted from the liver to the brain, particularly the hypothalamus. The efferent limbs of the response apparently rely on neural and/or humoral signals. Both selective sympathetic denervation of the liver and reduction in hepatic nitric oxide (NO) by inhibition of NO synthase (NOS) activity (mimicking a reduction in nitrergic neural signals) stimulate NHGU in the presence of hyperinsulinemia and hyperglycemia brought about by peripheral glucose infusion. In addition, electrical stimulation of the hypothalamus stimulates muscle glucose uptake, and sympathetic blockade prevents the increase in uptake. It is also possible that a humoral factor released either by the liver or muscle (a hepatokine or myokine) regulates glucose uptake by the opposing tissue. MGU, muscle glucose uptake; NE, norepinephrine.
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References

    1. Fagius J. Sympathetic nerve activity in metabolic control–some basic concepts. Acta Physiol Scand. 2003;177:337–43 - PubMed
    1. Scott EM, Greenwood JP, Vacca G, Stoker JB, Gilbey SG, Mary DA. Carbohydrate ingestion, with transient endogenous insulinaemia, produces both sympathetic activation and vasodilatation in normal humans. Clin Sci (Lond). 2002;102:523–9 - PubMed
    1. Vollmer K, Gardiwal H, Menge BA, Goetze O, Deacon CF, Schmidt WE, Holst JJ, Meier JJ. Hyperglycemia acutely lowers the postprandial excursions of glucagon-like Peptide-1 and gastric inhibitory polypeptide in humans. J Clin Endocrinol Metab. 2009;94:1379–85 - PubMed
    1. Krssak M, Brehm A, Bernroider E, Anderwald C, Nowotny P, Dalla Man C, Cobelli C, Cline GW, Shulman GI, Waldhausl W, et al. Alterations in postprandial hepatic glycogen metabolism in type 2 diabetes. Diabetes. 2004;53:3048–56 - PubMed
    1. Hwang JH, Perseghin G, Rothman DL, Cline GW, Magnusson I, Petersen KF, Shulman GI. Impaired net hepatic glycogen synthesis in insulin-dependent diabetic subjects during mixed meal ingestion. A 13C nuclear magnetic resonance spectroscopy study. J Clin Invest. 1995;95:783–7 - PMC - PubMed

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