|
| Status |
Public on Nov 25, 2009 |
| Title |
Low dose Leptin (25 ng/hr and 12.5 ng/hr) in ob/ob mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Ob/ob mice were given 0, 12.5 or 25 ng/hr leptin through an osmotic pump. After 12 days, livers RNA was prepared and illumina microarrays were done. We tested whether leptin can ameliorate diabetes independent of weight loss by defining the lowest dose at which leptin treatment of ob/ob mice reduces plasma [glucose] and [insulin]. We found that a leptin dose of 12.5 ng/hour significantly lowers blood glucose and that 25 ng/hour of leptin normalizes plasma glucose and insulin without significantly reducing body weight, thus establishing that leptin exerts its most potent effects on glucose metabolism. To find possible mediators of this effect, we profiled liver mRNA using microarrays and identified IGF Binding Protein 2 as being regulated by leptin with a similarly high potency. Over-expression of IGFBP2 by an adenovirus reversed diabetes in insulin resistant ob/ob, Ay/a and diet-induced obese mice (DIO), as well as insulin deficient streptozotocin-treated mice. Hyperinsulinemic clamp studies showed a three-fold improvement in hepatic insulin sensitivity following IGFBP2 treatment in ob/ob mice. These results show that IGFBP2 can regulate glucose metabolism, a finding with potential implications for the pathogenesis and treatment of diabetes.
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| |
|
| Overall design |
n=3 for zero and 25 ng/hr. n=2 for 12.5 ng/hr
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| |
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| Contributor(s) |
Friedman JM, Hedbacker K |
| Citation(s) |
20074524 |
| Submission date |
Nov 25, 2009 |
| Last update date |
Jun 14, 2018 |
| Contact name |
Kristina Hedbacker |
| E-mail(s) |
kristina.hedbaker@rockefeller.edu
|
| Organization name |
Rockefeller University
|
| Street address |
1230 York Avenue
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
|
| Samples (8)
|
|
| Relations |
| BioProject |
PRJNA120669 |
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