Hepatic portal venous delivery of a nitric oxide synthase inhibitor enhances net hepatic glucose uptake
- PMID: 18212022
- DOI: 10.1152/ajpendo.00184.2007
Hepatic portal venous delivery of a nitric oxide synthase inhibitor enhances net hepatic glucose uptake
Abstract
Hepatic portal venous infusion of nitric oxide synthase (NOS) inhibitors causes muscle insulin resistance, but the effects on hepatic glucose disposition are unknown. Conscious dogs underwent a hyperinsulinemic (4-fold basal) hyperglycemic (hepatic glucose load 2-fold basal) clamp, with assessment of liver metabolism by arteriovenous difference methods. After 90 min (P1), dogs were divided into two groups: control (receiving intraportal saline infusion; n = 8) and LN [receiving N(G)-nitro-L-arginine methyl ester (L-NAME), a nonspecific NOS inhibitor; n = 11] intraportally at 0.3 mg x kg(-1) x min(-1) for 90 min (P2). During the final 60 min of study (P3), L-NAME was discontinued, and five LN dogs received the NO donor SIN-1 intraportally at 6 mug x kg(-1) x min(-1) while six received saline (LN/SIN-1 and LN/SAL, respectively). Net hepatic fractional glucose extraction (NHFE) in control dogs was 0.034 +/- 0.016, 0.039 +/- 0.015, and 0.056 +/- 0.019 during P1, P2, and P3, respectively. NHFE in LN was 0.045 +/- 0.009 and 0.111 +/- 0.007 during P1 and P2, respectively (P < 0.05 vs. control during P2), and 0.087 +/- 0.009 and 0.122 +/- 0.016 (P < 0.05) during P3 in LN/SIN-1 and LN/SAL, respectively. During P2, arterial glucose was 204 +/- 5 vs. 138 +/- 11 mg/dl (P < 0.05) in LN vs. control to compensate for L-NAME's effect on blood flow. Therefore, another group (LNlow; n = 4) was studied in the same manner as LN/SAL, except that arterial glucose was clamped at the same concentrations as in control. NHFE in LNlow was 0.052 +/- 0.008, 0.093 +/- 0.023, and 0.122 +/- 0.021 during P1, P2, and P3, respectively (P < 0.05 vs. control during P2 and P3), with no significant difference in glucose infusion rates. Thus, NOS inhibition enhanced NHFE, an effect partially reversed by SIN-1.
Similar articles
-
Effects of the nitric oxide donor SIN-1 on net hepatic glucose uptake in the conscious dog.Am J Physiol Endocrinol Metab. 2008 Feb;294(2):E300-6. doi: 10.1152/ajpendo.00380.2007. Epub 2007 Nov 20. Am J Physiol Endocrinol Metab. 2008. PMID: 18029444
-
Role of the hepatic sympathetic nerves in the regulation of net hepatic glucose uptake and the mediation of the portal glucose signal.Am J Physiol Endocrinol Metab. 2006 Jan;290(1):E9-E16. doi: 10.1152/ajpendo.00184.2005. Epub 2005 Aug 16. Am J Physiol Endocrinol Metab. 2006. PMID: 16105863
-
Insulin sensitivity is mediated by the activation of the ACh/NO/cGMP pathway in rat liver.Am J Physiol Gastrointest Liver Physiol. 2004 Sep;287(3):G527-32. doi: 10.1152/ajpgi.00085.2004. Am J Physiol Gastrointest Liver Physiol. 2004. PMID: 15331351
-
Portal vs central glucose sensing in humans: the value of clinical models.Diabetes Nutr Metab. 2002 Oct;15(5):315. Diabetes Nutr Metab. 2002. PMID: 12625476 Review. No abstract available.
-
The HISS story overview: a novel hepatic neurohumoral regulation of peripheral insulin sensitivity in health and diabetes.Can J Physiol Pharmacol. 1999 Aug;77(8):553-62. Can J Physiol Pharmacol. 1999. PMID: 10543718 Review.
Cited by
-
Systemic inhibition of nitric oxide synthesis in non-diabetic individuals produces a significant deterioration in glucose tolerance by increasing insulin clearance and inhibiting insulin secretion.Diabetologia. 2013 May;56(5):1183-91. doi: 10.1007/s00125-013-2836-x. Epub 2013 Jan 31. Diabetologia. 2013. PMID: 23370528 Clinical Trial.
-
Regulation of hepatic glucose uptake and storage in vivo.Adv Nutr. 2012 May 1;3(3):286-94. doi: 10.3945/an.112.002089. Adv Nutr. 2012. PMID: 22585902 Free PMC article. Review.
-
A soluble guanylate cyclase-dependent mechanism is involved in the regulation of net hepatic glucose uptake by nitric oxide in vivo.Diabetes. 2010 Dec;59(12):2999-3007. doi: 10.2337/db10-0138. Epub 2010 Sep 7. Diabetes. 2010. PMID: 20823104 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous