HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Online-Only Appendix All Versions of this Article: db06-1142v1 56/5/1228    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Flowers, J. B. Articles by Attie, A. D. Search for Related Content PubMed PubMed Citation Articles by Flowers, J. B. Articles by Attie, A. D. Social Bookmarking                What's this?

Loss of Stearoyl-CoA Desaturase-1 Improves Insulin Sensitivity in Lean Mice but Worsens Diabetes in Leptin-deficient Obese Mice

¹Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI 53706
²Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706

Correspondence: attie{at}biochem.wisc.edu

The lipogenic gene stearoyl-CoA desaturase (SCD1) appears to be a promising new target for obesity-related diabetes as mice deficient in this enzyme are resistant to diet- and leptin deficiency-induced obesity. The BTBR mouse strain replicates many features of insulin resistance found in humans with excess visceral adiposity. Using the hyperinsulinemic-euglycemic clamp technique, we determined that insulin sensitivity was improved in heart, soleus muscle, adipose tissue, and liver of BTBR SCD1-deficient mice. We next determined if SCD1 deficiency could prevent diabetes in leptin-deficient BTBR mice. Loss of SCD1 in leptin^ob/ob mice unexpectedly accelerated the progression to severe diabetes; 6-wk fasting glucose increased approximately 70%. In response to a glucose challenge, Scd1^-/- leptin^ob/ob mice had insufficient insulin secretion, resulting in glucose intolerance. A morphologically distinct class of islets isolated from the Scd1^-/- leptin^ob/ob mice had reduced insulin content and increased triglycerides, free fatty acids, esterified cholesterol, and free cholesterol and also a much higher content of saturated fatty acids. We believe the accumulation of lipid is due to an up-regulation of lipoprotein lipase (20-fold) and Cd36 (167-fold) and downregulation of lipid oxidation genes in this class of islets. Therefore, although loss of Scd1 has beneficial effects on adiposity, this benefit may come at the expense of ß-cells, resulting in an increased risk of diabetes.

CiteULike

Del.icio.us

Digg

Reddit

Technorati