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Original Articles

Characterization of Insulin Resistance and NIDDM in Transgenic Mice With Reduced Brown Fat

  1. Andreas Hamann,
  2. Heike Benecke,
  3. Yannick Le Marchand-Brustel,
  4. Vedrana S Susulic,
  5. Bradford B Lowell and
  6. Jeffrey S Flier
  1. Division of Endocrinology and Metabolism, Beth Israel Hospital and Harvard Medical School Boston, Massachusetts
  2. Faculty of Medicine, Institut National de la Sante et de la Recherche Médicale Nice, France
  1. Address correspondence and reprint requests to Dr. Jeffrey S. Flier, Division of Endocrinology and Metabolism, Beth Israel Hospital, 330 Brookline Ave., Boston, MA 02215.
Diabetes 1995 Nov; 44(11): 1266-1273. https://doi.org/10.2337/diab.44.11.1266
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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.

  • Received April 20, 1995.
  • Revision received July 27, 1995.
  • Accepted July 27, 1995.
  • Copyright © 1995 by the American Diabetes Association

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November 1995, 44(11)
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Characterization of Insulin Resistance and NIDDM in Transgenic Mice With Reduced Brown Fat
Andreas Hamann, Heike Benecke, Yannick Le Marchand-Brustel, Vedrana S Susulic, Bradford B Lowell, Jeffrey S Flier
Diabetes Nov 1995, 44 (11) 1266-1273; DOI: 10.2337/diab.44.11.1266

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Characterization of Insulin Resistance and NIDDM in Transgenic Mice With Reduced Brown Fat
Andreas Hamann, Heike Benecke, Yannick Le Marchand-Brustel, Vedrana S Susulic, Bradford B Lowell, Jeffrey S Flier
Diabetes Nov 1995, 44 (11) 1266-1273; DOI: 10.2337/diab.44.11.1266
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