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Exercise training prevents endometrial hyperplasia and biomarkers for endometrial cancer in rat model of type 1 diabetes.

Al-Jarrah M, Matalka I, Aseri HA, Mohtaseb A, Smirnova IV, Novikova L, Stehno-Bittel L, Alkhateeb A - J Clin Med Res (2010)

Bottom Line: A 4-week treadmill training program was initiated with the development of diabetes.The expression of ERα increased significantly (p < 0.02) while the expression level of p16 decreased significantly (p < 0.04) in the diabetic sedentary group compared to the non-diabetic groups.Exercise training led to a reversal in the percentage of p16 and ERα positive cells in diabetic rats.

View Article: PubMed Central - PubMed

Affiliation: Department of Allied Medical Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Jordan.

ABSTRACT

Background: Endometrial cancer is one of the most common types of gynecologic cancers. The ability of exercise to reduce the risk of endometrial cancer in women with type 2 diabetes has been established, but no studies have examined this link in type 1 diabetes.A randomized, controlled animal study was designed using a standard rat model of type 1 diabetes. The goal of this study was to investigate the ability of exercise to prevent increased levels of endometrial cancer biomarkers, estrogen receptor (ERα) and p16, and endometrial hyperplasia associated with diabetes.

Methods: FORTY FEMALE RATS WERE RANDOMIZED INTO FOUR GROUPS: sedentary control, exercise control, sedentary or exercised diabetic. Diabetes was induced by alloxan injection. A 4-week treadmill training program was initiated with the development of diabetes. Endometrial tissues were evaluated for hyperplasia and ERα and p16 levels and subcellular localization using microscopy.

Results: Severe diabetes lead to hyperplasia in the endometrial tissue in 70% of sedentary diabetic rats. Exercise-trained diabetic rats and the non-diabetic rats displayed no hyperplasia. The expression of ERα increased significantly (p < 0.02) while the expression level of p16 decreased significantly (p < 0.04) in the diabetic sedentary group compared to the non-diabetic groups. Exercise training led to a reversal in the percentage of p16 and ERα positive cells in diabetic rats.

Conclusions: Severe diabetes leads to hyperplasia of the endometrial tissue and increased ERα levels and decreased p16 levels in rats, which can be prevented with aerobic exercise.

Keywords: Diabetes; Estrogen receptor alpha; P16; Endometrial hyperplasia; Endometrial cancer; Exercise.

No MeSH data available.


Related in: MedlinePlus

Comparison of p16 positive staining in four groups of rats. Tissue from sedentary control (SC) and exercised control (EC) rats had a greater area of p16-positive immunostaining. Diabetes (SD) reduced the amount of p16-staining when compared to the other three groups (* indicates p < 0.04), while exercise training of the diabetic animals (ED) increased the amount of p16 so that it was not statistically different from the control groups (# indicates significant difference between SD and ED).
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Figure 3: Comparison of p16 positive staining in four groups of rats. Tissue from sedentary control (SC) and exercised control (EC) rats had a greater area of p16-positive immunostaining. Diabetes (SD) reduced the amount of p16-staining when compared to the other three groups (* indicates p < 0.04), while exercise training of the diabetic animals (ED) increased the amount of p16 so that it was not statistically different from the control groups (# indicates significant difference between SD and ED).

Mentions: The p16 protein, a CDKN2A gene product, is known as a tumor suppressor protein. Decreases in the level of p16 have been linked with cancer, especially uterine and endometrium [26, 27]. Cells with positive staining for p16 from the control rats were found to have predominantly cytoplasmic staining with little nuclear localization, as described previously [28]. In contrast to the increase in the ERα levels in diabetic rats in this study, the amount of p16 decreased significantly from 20% of the total tissue area in the sedentary control group to 6% in the sedentary diabetic group (Figure 3, p < 0.04). The results showed that treadmill exercise training increased the area staining positive for p16 in the non-diabetic group from 20% to 26%, which was not a significant change (p < 0.53). In contrast, treadmill exercise training had a significant impact on the p16 levels of the endometrium from diabetic rats. The training protocol resulted in an increase in the area of positive p16 immunoreactivity from 6% to 17%, which was statistically significant (p < 0.04).


Exercise training prevents endometrial hyperplasia and biomarkers for endometrial cancer in rat model of type 1 diabetes.

Al-Jarrah M, Matalka I, Aseri HA, Mohtaseb A, Smirnova IV, Novikova L, Stehno-Bittel L, Alkhateeb A - J Clin Med Res (2010)

Comparison of p16 positive staining in four groups of rats. Tissue from sedentary control (SC) and exercised control (EC) rats had a greater area of p16-positive immunostaining. Diabetes (SD) reduced the amount of p16-staining when compared to the other three groups (* indicates p < 0.04), while exercise training of the diabetic animals (ED) increased the amount of p16 so that it was not statistically different from the control groups (# indicates significant difference between SD and ED).
© Copyright Policy - open access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3104659&req=5

Figure 3: Comparison of p16 positive staining in four groups of rats. Tissue from sedentary control (SC) and exercised control (EC) rats had a greater area of p16-positive immunostaining. Diabetes (SD) reduced the amount of p16-staining when compared to the other three groups (* indicates p < 0.04), while exercise training of the diabetic animals (ED) increased the amount of p16 so that it was not statistically different from the control groups (# indicates significant difference between SD and ED).
Mentions: The p16 protein, a CDKN2A gene product, is known as a tumor suppressor protein. Decreases in the level of p16 have been linked with cancer, especially uterine and endometrium [26, 27]. Cells with positive staining for p16 from the control rats were found to have predominantly cytoplasmic staining with little nuclear localization, as described previously [28]. In contrast to the increase in the ERα levels in diabetic rats in this study, the amount of p16 decreased significantly from 20% of the total tissue area in the sedentary control group to 6% in the sedentary diabetic group (Figure 3, p < 0.04). The results showed that treadmill exercise training increased the area staining positive for p16 in the non-diabetic group from 20% to 26%, which was not a significant change (p < 0.53). In contrast, treadmill exercise training had a significant impact on the p16 levels of the endometrium from diabetic rats. The training protocol resulted in an increase in the area of positive p16 immunoreactivity from 6% to 17%, which was statistically significant (p < 0.04).

Bottom Line: A 4-week treadmill training program was initiated with the development of diabetes.The expression of ERα increased significantly (p < 0.02) while the expression level of p16 decreased significantly (p < 0.04) in the diabetic sedentary group compared to the non-diabetic groups.Exercise training led to a reversal in the percentage of p16 and ERα positive cells in diabetic rats.

View Article: PubMed Central - PubMed

Affiliation: Department of Allied Medical Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Jordan.

ABSTRACT

Background: Endometrial cancer is one of the most common types of gynecologic cancers. The ability of exercise to reduce the risk of endometrial cancer in women with type 2 diabetes has been established, but no studies have examined this link in type 1 diabetes.A randomized, controlled animal study was designed using a standard rat model of type 1 diabetes. The goal of this study was to investigate the ability of exercise to prevent increased levels of endometrial cancer biomarkers, estrogen receptor (ERα) and p16, and endometrial hyperplasia associated with diabetes.

Methods: FORTY FEMALE RATS WERE RANDOMIZED INTO FOUR GROUPS: sedentary control, exercise control, sedentary or exercised diabetic. Diabetes was induced by alloxan injection. A 4-week treadmill training program was initiated with the development of diabetes. Endometrial tissues were evaluated for hyperplasia and ERα and p16 levels and subcellular localization using microscopy.

Results: Severe diabetes lead to hyperplasia in the endometrial tissue in 70% of sedentary diabetic rats. Exercise-trained diabetic rats and the non-diabetic rats displayed no hyperplasia. The expression of ERα increased significantly (p < 0.02) while the expression level of p16 decreased significantly (p < 0.04) in the diabetic sedentary group compared to the non-diabetic groups. Exercise training led to a reversal in the percentage of p16 and ERα positive cells in diabetic rats.

Conclusions: Severe diabetes leads to hyperplasia of the endometrial tissue and increased ERα levels and decreased p16 levels in rats, which can be prevented with aerobic exercise.

Keywords: Diabetes; Estrogen receptor alpha; P16; Endometrial hyperplasia; Endometrial cancer; Exercise.

No MeSH data available.


Related in: MedlinePlus