Differential roles of insulin and IGF-1 receptors in adipose tissue development and function

Jeremie Boucher, Samir Softic, Abdelfattah El Ouaamari, Megan T. Krumpoch, Andre Kleinridders, Rohit N. Kulkarni, Brian T. O'Neill, C. Ronald Kahn

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38 Scopus citations

Abstract

To determine the roles of insulin and insulin-like growth factor 1 (IGF-1) action in adipose tissue, we created mice lacking the insulin receptor (IR), IGF-1 receptor (IGF1R), or both using Cre-recombinase driven by the adiponectin promoter. Mice lacking IGF1R only (F-IGFRKO) had a ∼25% reduction in white adipose tissue (WAT) and brown adipose tissue (BAT), whereas mice lacking both IR and IGF1R (F-IR/IGFRKO) showed an almost complete absence of WAT and BAT. Interestingly, mice lacking only the IR (F-IRKO) had a 95% reduction in WAT, but a paradoxical 50% increase in BAT with accumulation of large unilocular lipid droplets. Both F-IRKO and F-IR/IGFRKO mice were unable to maintain body temperature in the cold and developed severe diabetes, ectopic lipid accumulation in liver and muscle, and pancreatic islet hyperplasia. Leptin treatment normalized blood glucose levels in both groups. Glucose levels also improved spontaneously by 1 year of age, despite sustained lipodystrophy and insulin resistance. Thus, loss of IR is sufficient to disrupt white fat formation, but not brown fat formation and/or maintenance, although it is required for normal BAT function and temperature homeostasis. IGF1R has only a modest contribution to both WAT and BAT formation and function.

Original languageEnglish (US)
Pages (from-to)2201-2213
Number of pages13
JournalDiabetes
Volume65
Issue number8
DOIs
StatePublished - Aug 1 2016

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Boucher, J., Softic, S., El Ouaamari, A., Krumpoch, M. T., Kleinridders, A., Kulkarni, R. N., O'Neill, B. T., & Kahn, C. R. (2016). Differential roles of insulin and IGF-1 receptors in adipose tissue development and function. Diabetes, 65(8), 2201-2213. https://doi.org/10.2337/db16-0212