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Publication : Insulin depletion leads to adipose-specific cell death in obese but not lean mice.

First Author  Loftus TM Year  1998
Journal  Proc Natl Acad Sci U S A Volume  95
Issue  24 Pages  14168-72
PubMed ID  9826672 Mgi Jnum  J:51283
Mgi Id  MGI:1314985 Doi  10.1073/pnas.95.24.14168
Citation  Loftus TM, et al. (1998) Insulin depletion leads to adipose-specific cell death in obese but not lean mice. Proc Natl Acad Sci U S A 95(24):14168-72
abstractText  Mutation of the obese gene produces obesity, hyperinsulinemia, and compensatory overexpression of the defective gene. As insulin activates obese gene expression, it seemed possible that hyperinsulinemia might be responsible for overexpression of the gene. To address this question we rapidly neutralized circulating insulin by injection of an insulin antibody. Unexpectedly, insulin depletion in obese (ob/ob or db/db) mice caused massive adipose RNA degradation confirmed by histological analysis to result from adipocyte cell death by a largely necrotic mechanism. This effect was not observed in lean littermates and was completely corrected by coadministration of insulin. Comparison of multiple tissues demonstrated that the effect was restricted to adipose tissue. Insulin depletion in obese mice by administration of streptozotocin also led to cell death, but this death was less extensive and appeared to be apoptotic in mechanism. Thus insulin may promote the survival side of the physiological balance between adipocyte survival and death.
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