Transcriptomics,Genomics

Dataset Information

56

Low dose Leptin (25 ng/hr and 12.5 ng/hr) in ob/ob mice


ABSTRACT: 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. Overall design: n=3 for zero and 25 ng/hr. n=2 for 12.5 ng/hr

INSTRUMENT(S): Illumina MouseRef-8 v2.0 expression beadchip

SUBMITTER: Kristina Hedbacker  

PROVIDER: GSE19185 | GEO | 2009-11-25

SECONDARY ACCESSION(S): PRJNA120669

REPOSITORIES: GEO

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Publications

Antidiabetic effects of IGFBP2, a leptin-regulated gene.

Hedbacker Kristina K   Birsoy Kivanç K   Wysocki Robert W RW   Asilmaz Esra E   Ahima Rexford S RS   Farooqi I Sadaf IS   Friedman Jeffrey M JM  

Cell metabolism 20100101 1


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 concentration. We found that a leptin dose of 12.5 ng/hr significantly lowers blood glucose and that 25 ng/hr of leptin normalizes plasma glucose and insulin without significantly reducing body weight, establishing that leptin exerts its most potent effects on glucose metabolism. To find possible mediators of this effec  ...[more]

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