NOTICE -- Login operations are currently offline due to an unscheduled disruption. We are waiting for LDAP services to be re-instated. We apologize for the inconvenience - June 24, 2021

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

An Z, Winnick JJ, Moore MC, Farmer B, Smith M, Irimia JM, Roach PJ, Cherrington AD
Diabetes. 2012 61 (10): 2433-41

PMID: 22688328 · PMCID: PMC3447895 · DOI:10.2337/db11-1816

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 µg/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 2× 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.

MeSH Terms (13)

Animals Blood Pressure Cyclic AMP Cyclic GMP Dogs Glucagon Glucose Glycogen Phosphorylase Glycogen Synthase Insulin Liver Portal Vein Signal Transduction

Connections (4)

This publication is referenced by other Labnodes entities: