Endocrine Abstracts

Background: The Ins2+/G32S mutation in the KINGS mouse drives beta-cell endoplasmic reticulum (ER) stress. The result of this is sexually dimorphic; males develop overt diabetes by 5-weeks (>16.7mM) whilst females remain normoglycemic. Previous studies have shown that high-fat feeding increases beta-cell ER stress, whilst GLP1-receptor agonists reduce this. We investigated whether altering ER stress could promote diabetes development in female KINGS mic...

Despite well-established sex differences in blood glucose homeostasis, female mice are highly underrepresented in preclinical diabetes research. Reasons for this may be the milder diabetic phenotype often seen in female mice and/or the assumption that the estrus cycle causes excessive variability in blood glucose concentrations. During this workshop talk we will discuss these points and the importance of accounting for sex differences. Using continuous glucose monitoring techn...

In the pancreas, PYY is expressed in a subpopulation of non-beta cells in the islets of Langerhans. The role of PYY-expressing cells in the adult pancreas is unknown. We generated a mouse model in which administration of diphtheria toxin (DT) produced specific ablation of PYY-expressing cells in the colon, pancreas and brainstem. Interestingly, DT administration to adult mice resulted in severe hyperglycaemia associated with significant loss of pancreatic insulin and disrupted...

The KINGS mouse harbours a mutant Ins2 which drives beta cell ER stress, however only males develop diabetes. Since diabetes incidence is lower in women and ER stress is implicated in human diabetes, we investigated the influence of oestrogen and testosterone in mediating sex differences in the KINGS mouse. To investigate the influence oestrogen (E2) and testosterone removal on glycaemic control, male (n =4-6) and female (n =9) KINGS mice underwent p...