Sex differences in glucose metabolism of streptozotocin-induced diabetes inbred mice (C57BL/6J)

Abstract

Considering that sex differences in glucose metabolism are observed in mice, researchers unconsciously use male mice to reduce variations by an estrogen cycle in female mice. In this study, we investigated the sex differences in glucose homeostasis in streptozotocin (STZ)-induced diabetes inbred mice (C57BL/6J). The C57BL/6J male and female mice were injected with or without STZ (40 mg/kg) for 5 consecutive days. Levels of fasting blood glucose (FBG), glycosylated hemoglobin (HbA1C), lipid profiles, oral glucose tolerance, and insulin resistance were measured at 3 and 6 weeks after STZ treatment. The FBG level in the STZ-induced male (M-STZ) group was significantly higher than that in the STZ-induced female (F-STZ) group during the entire experimental period. Furthermore, HbA1C and glucose tolerance levels in the M-STZ group were significantly higher than those in the F-STZ group at 3 and 6 weeks after STZ treatment. The glucagon/insulin ratio in the M-STZ group was significantly higher than that in the F-STZ group. Values of the homeostatic model assessment-insulin resistance, an indicator of β-cell function and insulin resistance, significantly increased in both the M-STZ and F-STZ groups at 3 weeks after STZ treatment. However, insulin resistance was observed in the M-STZ group, but not in the F-STZ group, at 6 weeks after STZ treatment. Taken together, our results indicate that glucose metabolism in the M-STZ group was worse than that in the F-STZ group, indicating that estrogen may have an important role in glucose metabolism by STZ treatment.

Brain-Body Control of Glucose Homeostasis—Insights From Model Organisms

“…Not only is vascular catheterization less technically challenging in the rat compared to the mouse, but mice require infusion of donor blood to replace erythrocytes and sustain hematocrit during clamping procedures, which results in larger colony number and more complex experimental design (137). Independently of rodent model choice, however, blood glucose assessments must take into consideration; strain (40,139), age (140,141), sex (142)(143)(144), fasting length (137,145) and husbandry (146)(147)(148) as all of these parameters differentially impact glucose homeostasis and the translatability of each model to human physiology (discussed in detail in 7,9). Nonmammalian species, while having critical distinctions in their mechanisms of glucose homeostasis, particularly with respect to the brain, offer unique opportunities afforded by their genetic tractability, lower cost, and fecundity.…”

Outbred Mice with Streptozotocin-Induced Diabetes Show Sex Differences in Glucose Metabolism

“…Type 2 diabetes is a disorder of glucose metabolism, with a metabolic phenotype that differs according to sex [ 10 ]. Our group reported that male inbred mice (C57BL/6J) had higher hyperglycemia than female mice after STZ injection [ 9 ]. In this study, we investigated whether the genetic background of the mice was important for the development of hyperglycemia and whether female hormones such as estrogen play a role in glucose metabolism after STZ injection.…”

“…In a previous study, we induced diabetes with streptozotocin (STZ) in C57BL/6J mice, which are preferentially used in studies with inbred mouse strains [ 9 ]. We confirmed that there were phenotypic differences according to sex in the diabetic groups.…”

Mouse Microglial Calcitonin Receptor Knockout Impairs Hypothalamic Amylin Neuronal pSTAT3 Signaling but Lacks Major Metabolic Consequences

“…Notably, there was an approximately 4.5-fold sex difference in insulin levels with females having lower values than males. In C57BL/6J mice, a clear sex difference in streptozotocin-induced diabetes has been described with females being more resilient to the treatment [34]. In human studies, women are generally more insulin sensitive than men, a difference which seems to diminish in the development of type 2 diabetes [35].…”