Selective overexpression in adipose cells in transgenic mice of GLUT4: the major insulin regulatable glucose transporter
1996
Gnudi, L. | Shepherd, P.R. | Tozzo, E. | Kahn, B.B.
To investigate the potential role of the GLUT4 glucose transporter in the pathogenesis of obesity and in in vivo glucose homeostasis, we developed a transgenic model in which we overexpressed the major insulin-regulatable glucose transporter specifically in white and brown adipose tissue. The adipose specific transgene was generated by ligating the human GLUT4 genomic sequence with the promoter-enhancer element of the fatty acid binding protein gene, aP2. Two lines of transgenic mice were created that overexpress GLUT4 six- to ninefold in white adipose tissue and three- to fivefold in brown adipose tissue. Transgenic mice showed increased glucose tolerance and lower fed insulin levels. In isolated adipocytes of transgenic mice from different fat depots (perigonadal, subcutaneous, and perirenal), basal glucose transport was twenty to thirty times greater and insulin-stimulated transport was two to four times greater than in cells from nontransgenic mice. Body lipid content was increased approximately threefold in transgenic mice versus nontransgenic mice of both sexes, and at different ages. Cell size was unaltered, but fat cell number was increased about twofold in transgenic versus nontransgenic mice. The adipose cell hyperplasia and enhanced glucose disposal with lower plasma insulin levels in transgenic mice is a unique model that dissociates obesity from insulin resistance.
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