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Date of Award
Campus Access Master's Thesis
Master of Science in Biological Sciences (MS)
Administrative Home Department
Department of Biological Sciences
Committee Member 1
Committee Member 2
Diabetes is a chronic metabolic disorder diagnosed with elevated blood glucose levels. A rise in blood glucose results from insufficient insulin secretion from pancreatic beta-cells and/or increased insulin resistance. Phosphofructokinase-1 (PFK-1) is a key enzyme in determining the glycolytic flux, which in turn triggers glucose-stimulated insulin secretion. The focus of the present study was to test differential PFK1 isoform expression in mouse islets and study their effects on insulin secretion under cytokine. Cytokine cocktail tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interferon gamma (IFN-γ) were used for mimicking diabetes. Real-time PCR showed that, of the three isozymes of PFK1 known to be expressed in islets, mRNAs encoding the muscle (PFKM) and platelet (PFKP) isozymes were most abundant in mouse islets, whereas mRNA encoding the liver isozyme (PFKL) was low. Interestingly, PFKP transcripts increased significantly in mouse islets that were exposed to cytokines, whereas the expression of PFKM mRNA had no significant change exposed to cytokines. In addition, similar to PFKM, silencing of PFKP reduced insulin secretion under normal growth conditions or cytokine treatment. However, glucose-stimulated insulin secretion was partially rescued under cytokine with silencing of PFKP compared to under normal growth condition. Our findings suggest that an increase in PFKP isoform expression in response to cytokines may protect β-cells and attenuate cytokine-induced inhibition of insulin secretion in diabetes.
Chen, Xinqian, "A CYTOKINE-INDUCED PLATELET-TYPE PHOSPHOFRUCTOKINASE (PFKP) REGULATING GLUCOSE-STIMULATED INSULIN SECRETION", Campus Access Master's Thesis, Michigan Technological University, 2020.