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Changes in Expression of Follicular Glucose Transporters May Be Involved in Ovarian Function Impairment during
Bin Xu1, Ying Hu2, Ya-Ting Luo1
1Department of Physiology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Sichuan, Chengdu, China.
Abstract:
Diabetes-induced hyperglycemia has a direct damaging effect on ovarian function. Despite its deadly impact on ovaries, the mechanism of this condition has not been fully elucidated. Glucose transporters are involved in glucose uptake and utilization. Many transporters have been detected in the ovaries, but their roles in diabetes-induced ovarian impairment are still unclear. In this study, the goal is to analyze glucose transporter expression in the ovarian follicles of type 1 diabetes mellitus patients and determine their roles within ovarian function impairment. The ovarian function of a mouse model of type 1 diabetes mellitus was evaluated by observing its estrus cycle, follicular development, and ovulation. Subtypes of the glucose transporter (GLUT2, GLUT3, GLUT4, SGLT1, and SGLT2), adenosine monophosphate-activated protein kinase (AMPK), and phosphorylated AMPK (Thr172) were found to be simultaneously present in follicle cells. Compared with nondiabetic control mice, the diabetic mice showed a dysregulated estrus cycle and a significantly higher number of abnormal ova. Furthermore, the expression of multiple glucose transporters was lower than that of phosphorylated AMPK. Phosphorylated AMPK possessed more follicular granulosa cells and oocytes of diabetic mice than in those of the control mice. These results suggest that diabetes-induced hyperglycemia reduces the capability of ovarian follicle cells by downregulating glucose transporter expression, causing decreased glucose uptake and energy deprivation. This impact can potentially impair egg maturation and ovulation.
Insights
Type 1 diabetes impairs ovarian function by reducing glucose transporter expression in follicles. This leads to decreased glucose uptake, energy deprivation, and abnormal egg maturation and ovulation.
Area of Science:
- Reproductive biology
- Endocrinology
- Metabolic disorders
Background:
- Diabetes-induced hyperglycemia negatively impacts ovarian function.
- The precise mechanisms underlying diabetes-related ovarian impairment are not fully understood.
- Glucose transporters are crucial for cellular glucose uptake and utilization, but their specific roles in ovarian dysfunction during diabetes remain unclear.
Purpose of the Study:
- To investigate glucose transporter expression in ovarian follicles of patients with type 1 diabetes mellitus.
- To elucidate the role of glucose transporters in diabetes-induced ovarian function impairment.
- To analyze the relationship between glucose transporters, adenosine monophosphate-activated protein kinase (AMPK), and ovarian function in a mouse model of type 1 diabetes.
Main Methods:
- Evaluation of ovarian function in a mouse model of type 1 diabetes mellitus, including estrus cycle, follicular development, and ovulation.
- Analysis of the expression of glucose transporter subtypes (GLUT2, GLUT3, GLUT4, SGLT1, SGLT2), AMPK, and phosphorylated AMPK (Thr172) in ovarian follicle cells.
- Comparison of these markers between diabetic and non-diabetic control mice.
Main Results:
- Diabetic mice exhibited dysregulated estrus cycles and a higher incidence of abnormal ova compared to controls.
- Expression of multiple glucose transporters was found to be downregulated in diabetic mice relative to phosphorylated AMPK.
- Increased levels of phosphorylated AMPK were observed in follicular granulosa cells and oocytes of diabetic mice.
Conclusions:
- Diabetes-induced hyperglycemia reduces ovarian follicle cell capability by downregulating glucose transporter expression.
- This downregulation leads to diminished glucose uptake and energy deficits within ovarian cells.
- The observed changes suggest a mechanism for impaired egg maturation and ovulation in diabetic conditions.
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