Date of Graduation

Summer 2021

Degree

Master of Science in Cell and Molecular Biology

Department

Biomedical Sciences

Committee Chair

Jianjie Wang

Keywords

glucose homeostasis, glucose tolerance, insulin resistance, nucleotide signaling, extracellular nucleotides, inflammation, inflammation-induced insulin resistance, P2Y2 Receptor

Subject Categories

Animal Experimentation and Research | Biochemical Phenomena, Metabolism, and Nutrition | Biochemistry | Cellular and Molecular Physiology | Endocrine System Diseases | Endocrinology | Laboratory and Basic Science Research | Medical Immunology | Medical Sciences | Molecular Biology | Nutritional and Metabolic Diseases | Physiological Processes | Physiology | Research Methods in Life Sciences | Translational Medical Research

Abstract

Recent insights into the pathological role of Nucleotide P2Y2 receptor suggest P2Y2R involvement in high fat diet-induced obesity and potentiates insulin resistance. However, these recent insights do not demonstrate how P2Y2R modulates glucose homeostasis under physiological conditions. Further, it remains unknown how sex biological factors influence P2Y2R receptor signaling in the regulation of glucose homeostasis. The research objective for the present study is to elucidate the novel roles of P2Y2 in fasting blood glucose and glucose tolerance (basal insulin sensitivity) under resting conditions in males and females. We expected that under physiological conditions P2Y2R signaling does not contribute to maintaining glucose homeostasis; we did not expect differences in fasting blood glucose and glucose tolerance between the wild type and the P2Y2R-/- mice. We further hypothesized that sex differences in fasting blood glucose and glucose tolerance would be present in wild type and P2Y2R-/- mice. We assessed fasting blood glucose (FBG) and glucose tolerance test in C57BL/6 (wild type) and P2Y2R-/- mice. Mice fasted for 5 hours, and blood was obtained from the tail to assess glucose levels using a glucometer. Mice received 2 g/kg body weight intraperitoneal (IP) injection of 20% dextrose. Glucose levels were measured at time 0 (fasting), then over 90 minutes after IP injection. In the current study, no significant difference was observed in FBG between wild type and P2Y2R-/- in males and females. However, it was observed that P2Y2R-/- males had impaired glucose tolerance relative to wild type, while females exhibited no differences. Sex differences in wild type, but not P2Y2R-/- mice in FBG were observed. However, sex differences in glucose tolerance were observed in WT and P2Y2R-/- mice, demonstrating females had improved glucose tolerance relative to males. The findings demonstrate P2Y2R in males contributes to physiological control of glucose homeostasis during a glucose tolerance test. Further, only WT mice demonstrated sex-specific differences in FBG, suggesting a sex-specific role for P2Y2R under fasting conditions.

Copyright

© Hailee Anne Marino

Open Access

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