Date of Graduation

Summer 2024

Degree

Master of Science in Cell and Molecular Biology

Department

Biomedical Sciences

Committee Chair

Randi Ulbricht

Abstract

Insulin resistance is the body's impaired ability to utilize endogenous and exogenous insulin to take up blood glucose and is associated with many clinical conditions including type 2 diabetes, hypertension, obesity, and cardiovascular disease. The cause of insulin resistance is still unknown; however, it is linked to inflammation. The activation of the purinergic P2Y2 receptor potentiates an inflammatory response under the pathogenesis of obesity and has adverse effects on glucose metabolism by regulating insulin resistance. The goal of this research is to investigate the effects of P2Y2 receptor activation on the downstream signaling pathways of the insulin receptor and glucose uptake. To determine if effects on glucose uptake are specific to the P2Y2 receptor, glucose tolerance testing (GTT) was performed in mice injected with UTP, a P2Y2 receptor ligand, and LPS, a potent activator of the inflammatory response. Glucose tolerance of male and female mice is increased when inflammation is induced by LPS. Male wildtype, but not P2Y2R knockout mice, display a reduced glucose tolerance in the presence of UTP but this effect is not observed in the presence of LPS. These effects seem to be primarily due to regulation of baseline glucose homeostasis rather than a response to challenge, as the effects are no longer present when normalized to baseline, fasting blood glucose levels. We also measured glucose transporter and insulin receptor gene expression and found no significant differences in their expression caused by inflammation or receptor activation. This research suggests that the effects of the P2Y2 receptor on glucose homeostasis are minimal, confined to males, and eliminated during acute inflammation.

Keywords

glucose homeostasis, glucose tolerance, inflammation, purinergic receptors

Subject Categories

Medical Molecular Biology

Copyright

© Jamila Makhloufi

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Open Access

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