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Humans With Rare Defects In The Insulin Receptor Signaling Pathway Provide Insight Into A Common Metabolic Defect

Date:
January 29, 2009
Source:
Journal of Clinical Investigation
Summary:
Analysis of individuals with rare, molecularly defined defects in the signaling pathway activated by the hormone insulin (which controls blood glucose levels) has provided new insight that might be applicable to the many individuals with obesity-related resistance to insulin, something that predisposes individuals to type 2 diabetes.

Analysis of individuals with rare, molecularly defined defects in the signaling pathway activated by the hormone insulin (which controls blood glucose levels), by a team of researchers at the University of Cambridge, United Kingdom, has provided new insight that might be applicable to the many individuals with obesity-related resistance to insulin, something that predisposes individuals to type 2 diabetes.

The importance of such studies and the questions that they raise are discussed in an accompanying commentary by Robert Hegele and Karen Reue.

The team, led by Robert Semple and David Savage, found that patients with generalized resistance to insulin because they either carry mutations in the insulin receptor gene or have inhibitory antibodies that bind the insulin receptor, have low levels of fats known as triglycerides in their blood and normal levels of "good" cholesterol (HDL cholesterol).

By contrast, two patients with mutations in the AKT2 gene, which generates a protein that is part of one of the signaling pathways activated when insulin binds the insulin receptor, were found to have increased levels of triglycerides in their blood and low levels of HDL cholesterol.

These and other human data reported here by the authors are consistent with current hypotheses, generated from mouse studies, that abnormal fat and cholesterol levels in individuals with obesity-related resistance to insulin are in fact caused by partial postreceptor liver insulin resistance, i.e., defects in only some signaling pathways downstream of the insulin receptor on liver cells.


Story Source:

The above story is based on materials provided by Journal of Clinical Investigation. Note: Materials may be edited for content and length.


Journal Reference:

  1. Semple et al. Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis. Journal of Clinical Investigation, Jan 29, 2009; DOI: 10.1172/JCI37432

Cite This Page:

Journal of Clinical Investigation. "Humans With Rare Defects In The Insulin Receptor Signaling Pathway Provide Insight Into A Common Metabolic Defect." ScienceDaily. ScienceDaily, 29 January 2009. <www.sciencedaily.com/releases/2009/01/090126210941.htm>.
Journal of Clinical Investigation. (2009, January 29). Humans With Rare Defects In The Insulin Receptor Signaling Pathway Provide Insight Into A Common Metabolic Defect. ScienceDaily. Retrieved August 23, 2014 from www.sciencedaily.com/releases/2009/01/090126210941.htm
Journal of Clinical Investigation. "Humans With Rare Defects In The Insulin Receptor Signaling Pathway Provide Insight Into A Common Metabolic Defect." ScienceDaily. www.sciencedaily.com/releases/2009/01/090126210941.htm (accessed August 23, 2014).

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