A cyclic guanosine monophosphate-dependent pathway can regulate net hepatic glucose uptake in vivo

Zhibo An, Jason J. Winnick, Mary C. Moore, Ben Farmer, Marta Smith, Jose M. Irimia, Peter Roach, Alan D. Cherrington

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

We previously showed that hepatic nitric oxide regulates net hepatic glucose uptake (NHGU), an effect that can be eliminated by inhibiting hepatic soluble guanylate cyclase (sGC), suggesting that the sGC pathway is involved in the regulation of NHGU. The aim of the current study was to determine whether hepatic cyclic guanosine monophosphate (cGMP) reduces NHGU. Studies were performed on conscious dogs with transhepatic catheters. A hyperglycemic- hyperinsulinemic clamp was established in the presence of portal vein glucose infusion. 8-Br-cGMP (50 mg/kg/min) was delivered intraportally, and either the glucose load to the liver (CGMP/GLC; n = 5) or the glucose concentration entering the liver (CGMP/GCC; n = 5) was clamped at 2X basal. In the control group, saline was given intraportally (SAL; n = 10), and the hepatic glucose concentration and load were doubled. 8-Br-cGMP increased portal blood flow, necessitating the two approaches to glucose clamping in the cGMP groups. NHGU (mg/kg/min) was 5.8 ± 0.5, 2.7 ± 0.5, and 4.8 ± 0.3, whereas the fractional extraction of glucose was 11.0 ± 1, 5.5 ± 1, and 8.5 ± 1% during the last hour of the study in SAL, CGMP/GLC, and CGMP/GCC, respectively. The reduction of NHGU in response to 8-Br-cGMP was associated with increased AMP-activated protein kinase phosphorylation. These data indicate that changes in liver cGMP can regulate NHGU under postprandial conditions.

Original languageEnglish (US)
Pages (from-to)2433-2441
Number of pages9
JournalDiabetes
Volume61
Issue number10
DOIs
StatePublished - Oct 2012
Externally publishedYes

Fingerprint

Cyclic GMP
Glucose
Liver
AMP-Activated Protein Kinases
Glucose Clamp Technique
Portal Vein
Nitric Oxide
Catheters
Phosphorylation

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

An, Z., Winnick, J. J., Moore, M. C., Farmer, B., Smith, M., Irimia, J. M., ... Cherrington, A. D. (2012). A cyclic guanosine monophosphate-dependent pathway can regulate net hepatic glucose uptake in vivo. Diabetes, 61(10), 2433-2441. https://doi.org/10.2337/db11-1816

A cyclic guanosine monophosphate-dependent pathway can regulate net hepatic glucose uptake in vivo. / An, Zhibo; Winnick, Jason J.; Moore, Mary C.; Farmer, Ben; Smith, Marta; Irimia, Jose M.; Roach, Peter; Cherrington, Alan D.

In: Diabetes, Vol. 61, No. 10, 10.2012, p. 2433-2441.

Research output: Contribution to journalArticle

An, Z, Winnick, JJ, Moore, MC, Farmer, B, Smith, M, Irimia, JM, Roach, P & Cherrington, AD 2012, 'A cyclic guanosine monophosphate-dependent pathway can regulate net hepatic glucose uptake in vivo', Diabetes, vol. 61, no. 10, pp. 2433-2441. https://doi.org/10.2337/db11-1816
An Z, Winnick JJ, Moore MC, Farmer B, Smith M, Irimia JM et al. A cyclic guanosine monophosphate-dependent pathway can regulate net hepatic glucose uptake in vivo. Diabetes. 2012 Oct;61(10):2433-2441. https://doi.org/10.2337/db11-1816
An, Zhibo ; Winnick, Jason J. ; Moore, Mary C. ; Farmer, Ben ; Smith, Marta ; Irimia, Jose M. ; Roach, Peter ; Cherrington, Alan D. / A cyclic guanosine monophosphate-dependent pathway can regulate net hepatic glucose uptake in vivo. In: Diabetes. 2012 ; Vol. 61, No. 10. pp. 2433-2441.
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