Lowering fasting blood glucose with non-dialyzable material of cranberry extract is dependent on host genetic background, sex and diet

Abstract

Background: Type 2 diabetes (T2D) is a polygenic metabolic disease, characterized by high fasting blood glucose (FBG). The ability of cranberry (CRN) fruit to regulate glycemia in T2D patients is well known. Here, a cohort of 13 lines of the genetically diverse Collaborative Cross (CC) mouse model was assessed for the effect of non-dialyzable material (NDM) of cranberry extract in lowering fasting blood glucose.

Methods: Eight-week-old mice were maintained on either a standard chow diet (control group) or a high-fat diet (HFD) for 12 weeks, followed by injections of intraperitoneal (IP) NDM (50 mg/kg) per mouse, three times a week for the next 6 weeks. Absolute FBG (mg/dl) was measured bi-weekly and percentage changes in FBG (%FBG) between weeks 0 and 12 were calculated.

Results: Statistical analysis showed a significant decrease in FBG between weeks 0 and 12 in male and female mice maintained on CHD. However, a non-significant increase in FBG values was observed in male and female mice maintained on HFD during the same period. Following administration of NDM during the following 6 weeks, the results show a variation in significant levels of FBG lowering between lines, male and female mice and under the different diets.

Conclusion: The results suggest that the efficacy of NDM treatment in lowering FGB depends on host genetic background (pharmacogenetics), sex of the mouse (pharmacosex), and diet (pharmacodiet). All these results support the need for follow-up research to better understand and implement a personalized medicine approach/utilization of NDM for reducing FBG.

Keywords: chow diet (CHD); collaborative cross (CC) mouse model; fasting blood glucose (FBG); high-fat diet (HFD); non-dialyzable material (NDM) of cranberry extract; type 2 diabetes (T2D).

FIGURE 1

Effect of NDM on total FBG (mg/dl) in female and male mice in the different diet groups. (A) and (B) show the total FBG (mg/dl) in female and male mice respectively in HFD and CHD groups.

FIGURE 2

Percentage changes (Delta) in fasting blood glucose (FBG) between weeks 12 and 0 of the female and male mice of 13 different collaborative cross (CC) lines maintained on either a standard chow diet (CHD) or a high‐fat diet (HFD) for 12 weeks. Panels A and B show the profiles of the female mice of 13 different CC lines maintained on CHD and HFD, respectively, for 12 weeks. Panels C and D show the profiles of the male mice of 13 CC lines maintained on CHD and HFD, respectively, for 12 weeks. In all the panels A–D, the x‐axis shows the thirteen CC lines, while the y‐axis represents the percentage (%) FBG differences between weeks 12 and 0 during the experiment.

FIGURE 3

Percentage changes (Delta) in fasting blood glucose (FBG) between weeks 12 and 18 of the female and male mice of 13 different collaborative cross (CC) mice maintained on a standard chow diet (CHD) or a high‐fat diet (HFD) for weeks 12 and subsequently treated with NDM for six weeks. Panels A and B show the profiles of the female mice of 13 different CC lines maintained a CHD and HFD, respectively, during the 6 weeks of NDM treatment. Panels C and D show the profiles of the male mice of 13 CC lines maintained on a CHD and HFD, respectively, during the 6 weeks of NDM treatment. In all the panels A–D, the x‐axis shows the thirteen CC lines, while the y‐axis represents the percentage (%) FBG differences between weeks 12 and 18 during the experiment.