Impact of local glucose and potassium variations on cellular responses: a potential mechanistic link between periodontitis and diabetes

Abusurur, Ruba (2022). Impact of local glucose and potassium variations on cellular responses: a potential mechanistic link between periodontitis and diabetes. University of Birmingham. M.Sc.

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Abstract

Periodontitis is a ubiquitous chronic inflammatory disease, in which the biofilm leads to an aberrant inflammatory response in susceptible individuals and if allowed to progress, can ultimately cause tooth loss.

Diabetes is a major healthcare concern, associated with high morbidity and mortality. It has been shown to have a strong bidirectional association with periodontitis, which is considered the sixth common complication of diabetes. Consequently, unstable diabetes increases the risk of periodontitis and successful management of periodontitis results in improved glycaemic control.

This thesis studied the impact of diabetes hyperglycaemia – increased glucose levels and hyperkalaemia– increased potassium levels on growth and virulence factor (haemolysins) expression of two bacteria strongly implicated in the pathogenesis of periodontitis Fusobacterium nucleatum subspecies polymorphum and Porphyromonas gingivalis (W83). The impact of hyperglycaemia on the growth, proliferation, and wound repair ability of a well characterised oral keratinocyte cell model system (H400 cells), as well as inflammatory response (IL-8 cytokine production) was also examined in cultures stimulated with these periodontal pathogens and high glucose levels.

Data indicated that high glucose increased the growth of F. nucleatum subspecies polymorphum (FNP ATCC10953) but not P. gingivalis PG (W83), while increased potassium levels did not affect bacterial growth of either pathogen. Representative gingival crevicular fluid levels of glucose and potassium, as found in diabetes patients, did not increase the haemolytic action of haemolysins. Increased glucose levels promoted the growth of oral keratinocytes (H400 cells), and the stimulation of these cells with heat inactivated FNP (ATCC10953) and PG(W83) led to production of IL-8. Cell migration of oral keratinocytes (H400 cells) increased with the elevation of glucose concentrations separately and with the stimulation of these cells with heat inactivated FNP (ATCC10953). Stimulation of these cells with PG (W83) with increased glucose concentration resulted in delayed wound closure.

In conclusion, increased numbers of FNP (ATCC10953) due to elevation in glucose concentration, will increase the cell inflammatory response, which will enhance inflammation, with hyper inflammation being an aetiological factor in periodontitis. Moreover, PG (W83) was concluded to delay wound healing with the increase in glucose concentration, so this may impact on epithelial barrier function which is proposed as important in periodontitis. For all these findings hyperglycaemia (high glucose) might have an impact on periodontitis pathogenesis.

Type of Work:

Thesis (Masters by Research > M.Sc.)

Award Type:

Masters by Research > M.Sc.

Supervisor(s):