TY - JOUR
T1 - Mouse Model of Erectile Dysfunction Due to Diet-Induced Diabetes Mellitus
AU - Xie, Donghua
AU - Odronic, Shelley I.
AU - Wu, Feihua
AU - Pippen, Anne
AU - Donatucci, Craig F.
AU - Annex, Brian H.
N1 - Funding Information:
This work was supported in part by a 2005 Bayer GSK Fellowship Award from the Sexual Medicine Society of North America to D. Xie and grant R01DK62997 from the National Institutes of Health (NIDDK) to B. H. Annex.
PY - 2007/7
Y1 - 2007/7
N2 - Objectives: To determine whether diet-induced diabetes mellitus (DM) in mice would reproduce the major features of human erectile dysfunction (ED) because DM is a significant risk factor in the development of ED. Methods: In total, 150 C57BL6 (bl6) mice were divided into six groups of 25 mice each. Of these 150 mice, 125 were fed a high-fat (45% of total calories) diet for the final 4 (group 2), 8 (group 3), 12 (group 4), 16 (group 5), or 22 (group 6) weeks. Group 1 was fed a normal diet. The mice were 22 to 25 weeks old at study termination. The corporal tissues were harvested and studied for endothelium-dependent and endothelium-independent vasoreactivity, endothelial and smooth muscle cell content by immunohistochemistry, nitric oxide synthase expression by nicotinamide adenine dinucleotide-diaphorase staining, and apoptosis by terminal deoxynucleotidyl transferase biotin-d-UTP nick-end labeling staining. Results: The blood glucose levels were greater in groups 2 to 6 compared with those in group 1. The vasoreactivity, endothelial cell content, and smooth muscle/collagen ratio were lower and apoptosis were greater in the DM mice (P = 0.0001, P = 0.10, P = 0.0002, P <0.001, and P <0.001, respectively). Significantly decreased nitric oxide synthase expression and significantly increased apoptosis (P <0.0001 each) was found in the high-fat diet mice. Conclusions: Corporal tissue from mice with diet-induced DM demonstrated many of the major functional, structural, and biochemical changes found in humans with ED. This model should serve as a valuable tool for advancing our understanding of the role DM plays in the pathogenesis of ED.
AB - Objectives: To determine whether diet-induced diabetes mellitus (DM) in mice would reproduce the major features of human erectile dysfunction (ED) because DM is a significant risk factor in the development of ED. Methods: In total, 150 C57BL6 (bl6) mice were divided into six groups of 25 mice each. Of these 150 mice, 125 were fed a high-fat (45% of total calories) diet for the final 4 (group 2), 8 (group 3), 12 (group 4), 16 (group 5), or 22 (group 6) weeks. Group 1 was fed a normal diet. The mice were 22 to 25 weeks old at study termination. The corporal tissues were harvested and studied for endothelium-dependent and endothelium-independent vasoreactivity, endothelial and smooth muscle cell content by immunohistochemistry, nitric oxide synthase expression by nicotinamide adenine dinucleotide-diaphorase staining, and apoptosis by terminal deoxynucleotidyl transferase biotin-d-UTP nick-end labeling staining. Results: The blood glucose levels were greater in groups 2 to 6 compared with those in group 1. The vasoreactivity, endothelial cell content, and smooth muscle/collagen ratio were lower and apoptosis were greater in the DM mice (P = 0.0001, P = 0.10, P = 0.0002, P <0.001, and P <0.001, respectively). Significantly decreased nitric oxide synthase expression and significantly increased apoptosis (P <0.0001 each) was found in the high-fat diet mice. Conclusions: Corporal tissue from mice with diet-induced DM demonstrated many of the major functional, structural, and biochemical changes found in humans with ED. This model should serve as a valuable tool for advancing our understanding of the role DM plays in the pathogenesis of ED.
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U2 - 10.1016/j.urology.2007.02.060
DO - 10.1016/j.urology.2007.02.060
M3 - Article
C2 - 17656247
AN - SCOPUS:34447507666
SN - 0090-4295
VL - 70
SP - 196
EP - 201
JO - Urology
JF - Urology
IS - 1
ER -