The role of hepatic insulin receptors in the regulation of glucose production
- PMID: 15864342
- PMCID: PMC1087191
- DOI: 10.1172/JCI25152
The role of hepatic insulin receptors in the regulation of glucose production
Abstract
The inability of insulin to suppress hepatic glucose production (HGP) is a key defect found in type 2 diabetes. Insulin inhibits HGP through both direct and indirect means, the latter of which include inhibition of glucagon secretion, reduction in plasma nonesterified fatty acid level, decrease in the load of gluconeogenic substrates reaching the liver, and change in neural signaling to the liver. Two studies in this issue of the JCI demonstrate that selective changes in the expression of insulin receptors in mouse liver do not have a detectable effect on the ability of insulin to inhibit HGP (see the related articles beginning on pages 1306 and 1314). These provocative data suggest that the indirect effects of insulin on the liver are the primary determinant of HGP in mice.
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Comment on
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Severe impairment in liver insulin signaling fails to alter hepatic insulin action in conscious mice.J Clin Invest. 2005 May;115(5):1306-13. doi: 10.1172/JCI23109. J Clin Invest. 2005. PMID: 15864350 Free PMC article.
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Restoration of liver insulin signaling in Insr knockout mice fails to normalize hepatic insulin action.J Clin Invest. 2005 May;115(5):1314-22. doi: 10.1172/JCI23096. J Clin Invest. 2005. PMID: 15864351 Free PMC article.
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