World J Mens Health.  2019 May;37(2):210-218. 10.5534/wjmh.180057.

Comparison of Improving Effects for Diabetic Erectile Dysfunction according to the Anti-Glycemic Agents: Phlorizin and Insulin

• Park J
• Kwon O
• Cho SY
• Cho MC
• Paick JS
• Kim SW

• KMID: 2443236
• DOI: http://doi.org/10.5534/wjmh.180057

Abstract

PURPOSE
To compare the improving effects of diabetic erectile dysfunction with two anti-glycemic agents; phlorizin and insulin.
MATERIALS AND METHODS
Sixty Sprague-Dawley rats were divided into four groups (n=15 in each group): normal control (C), untreated diabetic rats (D), and diabetic rats treated by phlorizin (P) or insulin (I). Ten weeks after the diabetic induction using an injection of streptozotocin (55 mg/kg), four weeks of diabetic control was conducted. Erectile response, Western blot, and immunohistochemistry were assessed.
RESULTS
During the experiment, the C-group showed continuous weight gain, while the other groups suffered from weight loss. After start of diabetic control, the body weight of I-group was increased; whereas, there was no meaningful change in the P-group. Meanwhile, comparable blood glucose levels were achieved in the P- and I-groups. The erectile response was markedly decreased in the D-group, whereas the P- and I-groups were similar as good as the C-group. In addition, D-group showed the significant decrease in the cavernosal smooth muscle content and increased apoptosis. Platelet endothelial cell adhesion molecule-1 protein expression, phosphorylation of endothelial nitric oxide synthase and myosin phosphatase target subunit 1 were significantly distorted in the D-group, while the P- and I-groups were comparable with the C-group.
CONCLUSIONS
Phlorizin treatment resulted in the improvement of erectile function as same as insulin despite the lack of anabolic weight gains. These results suggest that control of blood glucose level rather than a type of anti-glycemic agents is more important for the prevention and treatment of diabetic erectile dysfunction

Keyword

Diabetes complications; Erectile dysfunction; Insulin; Phlorizin

MeSH Terms

Animals
Antigens, CD31
Apoptosis
Blood Glucose
Blotting, Western
Body Weight
Diabetes Complications
Erectile Dysfunction*
Immunohistochemistry
Insulin*
Male
Muscle, Smooth
Myosin-Light-Chain Phosphatase
Nitric Oxide Synthase Type III
Phlorhizin*
Phosphorylation
Rats
Rats, Sprague-Dawley
Streptozocin
Weight Gain
Weight Loss
Antigens, CD31
Blood Glucose
Insulin
Myosin-Light-Chain Phosphatase
Nitric Oxide Synthase Type III
Phlorhizin
Streptozocin

Figure

• 

  Fig. 1 Mean body weight (A) and mean blood glucose levels (B) of each group during the experimental period after the induction of diabetes. (A) The C group showed continuous weight gain, while the other groups displayed significant weight loss during the ten weeks following diabetic induction. After the start of treatment, the body weight of the I group increased; however, there was no meaningful change in the P group. (B) The C group showed a constantly low glucose level, while the levels in the other groups reached around 500 to 600 mg/dL during the ten weeks after the induction of diabetes. After the start of treatment, the glucose levels of the P and I groups were similarly decreased to under 400 mg/dL. C: normal control, I: diabetes mellitus treated with insulin, P: diabetes mellitus treated with phlorizin.

• 

  Fig. 2 Comparison of the erectile parameters of each group at 10 Hz. Changes in the ICP adjusted for MAP (ICP/MAP) (A) and changes in the AUC adjusted for MAP (AUC/MAP) (B). ICP: intracavernosal pressure, MAP: mean arterial pressure, AUC: area under the curve, C: normal control, D: untreated diabetic rats, P: diabetes mellitus treated with phlorizin, I: diabetes mellitus treated with insulin. ap<0.05 vs. D group, bp<0.05 vs. C group.

• 

  Fig. 3 α-SMA expression in penile sections. The densitometric analysis and representative images of the α-SMA immunohistochemical staining are shown. (E) The percentages of the smooth muscle cell component (% α-SMA) significantly decreased in the D group (B) when compared with the C (A), P (C), and I (D) groups. α-SMA: alpha-smooth muscle actin, D: untreated diabetic rats, C: normal control, P: diabetes mellitus treated with phlorizin, I: diabetes mellitus treated with insulin. ap<0.05 vs. D group.

• 

  Fig. 4 Comparison of the apoptotic indices across the groups. The results are expressed as the apoptotic cell density (cells/mm2). The apoptotic activity was detected by in situ fluorescein labeling of DNA fragments using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. (E) The apoptotic cell density was significantly increased in the D group (B) when compared with the C (A), P (C), and I (D) groups. C: normal control, D: untreated diabetic rats, P: diabetes mellitus treated with phlorizin, I: diabetes mellitus treated with insulin. ap<0.05 vs. D group.

• 

  Fig. 5 Western blot analyses for PECAM-1 (A), phosphor-eNOS and total eNOS (B), and phosphor-MYPT-1 and total MYPT-1 (C). β-actin serves as a control. Representative blots are shown in the upper panel, while the densitometric analysis is shown in the bottom panel. PECAM-1: platelet and endothelial cell adhesion molecule 1, eNOS: endothelial constitutive nitric oxide synthase, MYPT-1: phosphorylated myosin phosphatase target subunit 1, C: normal control, D: untreated diabetic rats, P: diabetes mellitus treated with phlorizin, I: diabetes mellitus treated with insulin. ap<0.05 vs. D group.

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