Adaptive genetic variation, stress and glucose regulation

Area of Science:

• Zoology
• Genetics
• Physiology

Background:

• Elevated glucose and insulin levels are indicators of type 2 diabetes and metabolic syndrome.
• Genetic susceptibility to common conditions may reflect adaptations to historical environmental factors.
• Mammalian species with diverse environmental exposures may harbor similar genetic variants.

Purpose of the Study:

• To investigate glucose regulation in two deer mouse species, Peromyscus maniculatus bairdii (BW) and Peromyscus polionotus subgriseus (PO).
• To identify genetic factors contributing to differences in glucose regulation between these species, particularly in males.
• To explore the role of stress response and Y chromosome variation in interspecific glucose regulation differences.

Main Methods:

• Comparative analysis of glucose regulation in two deer mouse species (BW and PO).
• Assessment of insulin levels, insulin response, non-fasted glucose levels, and glucose challenge response in males and females.
• Analysis of consomic animals and the effect of glucocorticoid synthesis inhibitors on glucose regulation.

Main Results:

• PO mice exhibited superior glucose regulatory ability compared to BW mice, especially in males.
• Both species showed equivalent insulin levels/responses and non-fasted glucose levels.
• Y chromosome variation was implicated as the genetic cause for male-specific glucose regulatory differences.
• Fasting, handling, and elevated glucocorticoid (GC) levels in PO males significantly influenced glucose regulation, suggesting a stress-mediated response.

Conclusions:

• Interspecific differences in glucose regulation between deer mouse species are influenced by Y chromosome variation and stress response.
• PO males possess alleles that attenuate the glucocorticoid response, leading to better glucose control under stress.
• These findings suggest that similar genetic variants related to glucose regulation and stress response may exist in humans.