Characterization of Insulin Resistance and NIDDM in Transgenic Mice With Reduced Brown Fat
Abstract
We recently created a new model of murine obesity through transgenic ablation of brown adipose tissue (BAT) using a tissue-specific toxigene (6). The goal of the present study was to further define the altered glucose homeostasis and insulin resistance in these transgenic animals. Despite an ∼30% increase in total body lipid, no abnormalities were observed in 6-week-old transgenic animals. At the age of 22–26 weeks, marked obesity in transgenic mice was associated with significant increases in blood glucose and plasma insulin levels and an abnormal response to both intraperitoneal glucose and insulin tolerance tests. Glucose transport in soleus muscle was reduced, with the response to insulin stimulation blunted by up to 85% in males and 55% in females. The total number of insulin receptors was decreased by 36% in muscle and 59% in adipose tissue of transgenic animals. Insulin receptor tyrosine kinase activity, which was assessed following maximal insulin stimulation in vivo, was reduced in transgenic animals by 59% in muscle and 56% in fat. GLUT4 mRNA and protein was unchanged in muscle of transgenic animals compared with in that of controls but was significantly reduced in adipose tissue. In conclusion, primary BAT deficiency results in the development of glucose intolerance or diabetes and severe insulin resistance with both receptor and postreceptor components. These animals should be a useful model for studies of obesity-linked diabetes and insulin resistance and related complications.
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Several animal models of obesity and insulin resistance show significantly higher levels of TNFα mRNA and protein compared with their lean counterparts.
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- Authors
- Hamann, A., Benecke, H., Marchand-Brustel, Y. L., Susulic, V. S., Lowell, B. B., & Flier, J. S.
- Affiliations
- Harvard University (US)
- Faculty of Medicine, Institut National de la Sante et de la Recherche Médicale Nice, France
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 1995-11-01
- Volume
- 44
- Issue
- 11
- Pages
- 1266-1273
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2056354107
- Cited by
- 89
- References
- 0
- Citations by year
- 2026: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2017: 1 · 2016: 1 · 2015: 3 · 2013: 1 · 2012: 1
- FWCI
- 5.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k08dk002119-05, 5r01dk046930-10)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 46930, DK-02119-03, DK28082)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- insulin resistance, type 2 diabetes, brown adipose tissue, transgenic mice, obesity, glucose homeostasis, impaired glucose tolerance, insulin tolerance test, glucose transport, soleus muscle, insulin receptor, insulin receptor tyrosine kinase, GLUT4, adipose tissue, diabetes model
- MeSH terms
- Adipose Tissue, Aging, Animals, Biological Transport, Blood Glucose, Adipose Tissue, Brown, Cell Membrane, Deoxyglucose, Diabetes Mellitus, Diabetes Mellitus, Type 2, Diphtheria Toxin, Female, Glucose Tolerance Test, Insulin, Insulin Resistance, Male, Mice, Transgenic, Monosaccharide Transport Proteins, Muscle Proteins, Obesity, Receptor, Insulin, Reference Values, RNA, Messenger, Sex Characteristics, Tumor Necrosis Factor-alpha, Gene Expression, Muscle, Skeletal, Glucose Transporter Type 4, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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