Journal article
Differential Roles of Insulin and IGF-1 Receptors in Adipose Tissue Development and Function
Diabetes (New York, N.Y.), Vol.65(8), pp.2201-2213
08/2016
DOI: 10.2337/db16-0212
PMCID: PMC4955980
PMID: 27207537
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.
Details
- Title: Subtitle
- Differential Roles of Insulin and IGF-1 Receptors in Adipose Tissue Development and Function
- Creators
- Jeremie Boucher - Section on Integrative Physiology and Metabolism, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MASamir Softic - Section on Integrative Physiology and Metabolism, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MAAbdelfattah El Ouaamari - Islet Cell and Regenerative Medicine, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MAMegan T Krumpoch - Section on Integrative Physiology and Metabolism, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MAAndre Kleinridders - Section on Integrative Physiology and Metabolism, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MARohit N Kulkarni - Islet Cell and Regenerative Medicine, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MABrian T O'Neill - Section on Integrative Physiology and Metabolism, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MAC Ronald Kahn - Section on Integrative Physiology and Metabolism, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA c.ronald.kahn@joslin.harvard.edu
- Resource Type
- Journal article
- Publication Details
- Diabetes (New York, N.Y.), Vol.65(8), pp.2201-2213
- DOI
- 10.2337/db16-0212
- PMID
- 27207537
- PMCID
- PMC4955980
- ISSN
- 0012-1797
- eISSN
- 1939-327X
- Grant note
- R01 DK031036 / NIDDK NIH HHS R01 DK067536 / NIDDK NIH HHS R01 DK033201 / NIDDK NIH HHS P30 DK036836 / NIDDK NIH HHS K08 DK100543 / NIDDK NIH HHS T32 DK007260 / NIDDK NIH HHS R01 DK082659 / NIDDK NIH HHS R37 DK031036 / NIDDK NIH HHS R01 DK103215 / NIDDK NIH HHS P30 DK057521 / NIDDK NIH HHS K12 HD000850 / NICHD NIH HHS
- Language
- English
- Date published
- 08/2016
- Academic Unit
- Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984094400302771
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