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α3(V) Collagen is critical for glucose homeostasis in mice due to effects in pancreatic islets and peripheral tissues
Guorui Huang, … , Andras Nagy, Daniel S. Greenspan
Guorui Huang, … , Andras Nagy, Daniel S. Greenspan
Published January 10, 2011
Citation Information: J Clin Invest. 2011;121(2):769-783. https://doi.org/10.1172/JCI45096.
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Research Article Metabolism

α3(V) Collagen is critical for glucose homeostasis in mice due to effects in pancreatic islets and peripheral tissues

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Abstract

Collagen V, broadly expressed as α1(V)2α2(V) heterotrimers that regulate collagen fibril geometry and strength, also occurs in some tissues, such as white adipose tissue (WAT), pancreatic islets, and skeletal muscle, as the poorly characterized α1(V) α2(V) α3(V) heterotrimer. Here, we investigate the role of α3(V) collagen chains by generating mice with a null allele of the α3(V) gene Col5a3 (Col5a3–/– mice). Female Col5a3–/– mice had reduced dermal fat and were resistant to high-fat diet–induced weight gain. Male and female mutant mice were glucose intolerant, insulin-resistant, and hyperglycemic, and these metabolic defects worsened with age. Col5a3–/– mice demonstrated decreased numbers of pancreatic islets, which were more susceptible to streptozotocin-induced apoptosis, and islets isolated from mutant mice displayed blunted glucose-stimulated insulin secretion. Moreover, Col5a3–/– WAT and skeletal muscle were defective in glucose uptake and mobilization of intracellular GLUT4 glucose transporter to the plasma membrane in response to insulin. Our results underscore the emerging view of the importance of ECM to the microenvironments that inform proper development/functioning of specialized cells, such as adipocytes, β cells, and skeletal muscle.

Authors

Guorui Huang, Gaoxiang Ge, Dingyan Wang, Bagavathi Gopalakrishnan, Delana H. Butz, Ricki J. Colman, Andras Nagy, Daniel S. Greenspan

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Figure 9

Aberrations in insulin/IGF-1 signaling components and PPAR-γ levels in Col5a3–/– peripheral tissues.

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Aberrations in insulin/IGF-1 signaling components and PPAR-γ levels in C...
(A) Representative immunoblots are shown of soleus muscle and epididymal fat pad extracts from wild-type and Col5a3–/– mice that had been injected with PBS (–) or insulin (+). Blots were stained with antibodies to IRS2, Akt, or phospho-Akt (Ser 473). Blots were also stained with anti–β-actin as a loading control. (B and C) Immunoblots were repeated 3 times, from 3 independent tissue preps (from different mice). Films were scanned, and results were quantified for (B) phospho-Akt and (C) IRS2, using NIH ImageJ software. In each histogram, results are normalized for values of insulin-treated wild-type mice, and Col5a3–/– values are given ± SEM. *P < 0.05; ***P < 0.001. (D) An immunoblot shows markedly decreased PPAR-γ levels in adipose of Col5a3–/– mice injected with PBS (–) or insulin (+).

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