Sexual Dimorphism in Glucose Metabolism in Type 2 Diabetic Mice
- Diabetic Kidney Disease: Basic - II
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
- de Ponte, Mariana Charleaux, Universidade de Sao Paulo Instituto de Ciencias Biomedicas, Sao Paulo, São Paulo, Brazil
- Thieme, Karina, Universidade de Sao Paulo Instituto de Ciencias Biomedicas, Sao Paulo, São Paulo, Brazil
The prevalence of non-insulin-dependent diabetes has grown enormously over the last three decades and today this complication is a major global concern. According to the World Health Organization, the percentage of deaths attributed to high blood glucose is greater in males than females. This fact translates to experimental models of type 2 diabetes, in which obese male show increased blood glucose levels in comparison to female, despite the same degree of obesity. However, the mechanisms underlying this observation are still unclear. Thus, the aim of this study is to investigate the sexual dimorphism in glucose metabolism in BTBR WT and ob/ob mice.
The mice had blood glucose and body weight evaluated every two weeks. At the 16th week of age, euthanasia was performed to collect urine, liver and the kidneys. Albuminuria and gene expression of glucose metabolism enzymes were further performed.
Preliminary data show that BTBR ob/ob mice, independently of sex, presented increased body weight in comparison to corresponding WT mice, but obese male were hyperglycemic than female throughout the experimental protocol. Diabetes and obesity induced albuminuria equally between males and females, which confirms loss of kidney function. In the liver, male and female BTBR ob/ob mice showed decreased Pck1 and increased Fbp1 transcript levels, suggesting alteration of the gluconeogenesis pathway. However, female BTBR ob/ob mice had increased liver Pkm transcript levels than the corresponding male. In addition, liver Pkm transcript levels positively correlated with the blood glucose levels, which indicates sexual dimorphism in liver glycolysis. In the kidney, increased gene expression of the gluconeogenesis enzymes were observed in obese mice independently of sex, however, Hk1, Pkm and Pfkp transcript levels were upregulated only in females. Moreover, kidney Pfkp transcript levels positively correlated with blood glucose levels, suggesting also sexual dimorphism in kidney glycolysis. Gene expression of glucose transporters in the proximal tubule, SGLT2 and GLUT2, were only affected by obesity and diabetes and not by sex.
Collectively, these data show that there is a sexual dimorphism in gene expression of glycolysis enzymes in both liver and kidney, which may be associated with differences in blood glucose levels of male and female BTBR ob/ob.
- Government Support – Non-U.S.