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Brown adipose tissue–specific insulin receptor knockout shows diabetic phenotype without insulin resistance
Carmen Guerra, … , C. Ronald Kahn, Manuel Benito
Carmen Guerra, … , C. Ronald Kahn, Manuel Benito
Published October 15, 2001
Citation Information: J Clin Invest. 2001;108(8):1205-1213. https://doi.org/10.1172/JCI13103.
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Article

Brown adipose tissue–specific insulin receptor knockout shows diabetic phenotype without insulin resistance

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Abstract

Although insulin regulates metabolism in both brown and white adipocytes, the role of these tissues in energy storage and utilization is quite different. Recombination technology using the Cre-loxP approach allows inactivation of the insulin receptor in a tissue-specific manner. Mice lacking insulin receptors in brown adipocytes show an age-dependent loss of interscapular brown fat but increased expression of uncoupling protein-1 and -2. In parallel, these mice develop an insulin-secretion defect resulting in a progressive glucose intolerance, without insulin resistance. This model provides direct evidence for not only a role for the insulin receptors in brown fat adipogenesis, the data also suggest a novel role of brown adipose tissue in the regulation of insulin secretion and glucose homeostasis.

Authors

Carmen Guerra, Paloma Navarro, Angela M. Valverde, Monica Arribas, Jens Brüning, Leslie P. Kozak, C. Ronald Kahn, Manuel Benito

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Figure 1

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Structure and expression of the UCP-1-Cre transgene. (a) The Cre cDNA se...
Structure and expression of the UCP-1-Cre transgene. (a) The Cre cDNA sequence was included at the BglII site of the first exon of UCP-1 gene. The length of 5′ UTR of the UCP-1 gene was 8.4 kb. Exons 3, 4, 5, and 6 of the UCP-1 gene were also incorporated downstream of the Cre cDNA sequence. (b) Representative Northern blot analysis of total RNA isolated from several tissues of the two transgenic lines (lines 13 and 14) of mice carrying a UCP-1-Cre DNA construct described in a and C57BL/6J (B6) control mouse. Blots were hybridized with a full-length Cre cDNA probe.
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