Mice lacking the proton channel Hv1 exhibit sex-specific differences in glucose homeostasis
| Autor: | Yingtang Gao, Xiaomin Su, Jinzhi Li, Huimin Pang, Yuzhou Wang, Shu Jie Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty IPITT intraperitoneal (i.p.)insulin tolerance test Pygl glycogen phosphorylase Pck1 phosphoenolpyruvate carboxykinase-1 Carbohydrate metabolism Biochemistry Ion Channels Mice Gck glucokinase Internal medicine voltage-gated proton channel medicine Glucose homeostasis glucose homeostasis Animals sex dimorphism Molecular Biology Testosterone IPGTT intraperitoneal (i.p.) glucose tolerance test Mice Knockout G6pc glucose-6-phosphatase Sex Characteristics KO knockout biology Glucokinase Gluconeogenesis Cell Biology medicine.disease IRS1 Insulin receptor Endocrinology Gene Expression Regulation Liver testosterone biology.protein IRS1 insulin receptor substrate 1 Female Metabolic syndrome Glycolysis Glucose 6-phosphatase Hv1 PI3K phosphoinositide 3-kinase Research Article Signal Transduction |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 1083-351X 0021-9258 |
| Popis: | Sex as a physiologic factor has a strong association with the features of metabolic syndrome. Our previous study showed that loss of the voltage-gated proton channel Hv1 inhibits insulin secretion and leads to hyperglycemia and glucose intolerance in male mice. However, there are significant differences in blood glucose between male and female Hv1-knockout (KO) mice. Here, we investigated the differences in glucose metabolism and insulin sensitivity between male and female KO mice and how sex steroids contribute to these differences. We found that the fasting blood glucose in female KO mice was visibly lower than that in male KO mice, which was accompanied by hypotestosteronemia. KO mice in both sexes exhibited higher expression of gluconeogenesis-related genes in liver compared with WT mice. Also, the livers from KO males displayed a decrease in glycolysis-related gene expression and an increase in gluconeogenesis-related gene expression compared with KO females. Furthermore, exogenous testosterone supplementation decreased blood glucose levels in male KO mice, as well as enhancing insulin signaling. Taken together, our data demonstrate that knockout of Hv1 results in higher blood glucose levels in male than female mice, despite a decreased insulin secretion in both sexes. This sex-related difference in glucose homeostasis is associated with the glucose metabolism in liver tissue, likely due to the physiological levels of testosterone in KO male mice. |
| Databáze: | OpenAIRE |
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