Funded Research

Despite increased use of continuous glucose monitoring (CGM) and insulin pumps, most pregnant women with type 1 diabetes struggle to manage their glucose levels in pregnancy. Many deliver large birthweight babies and experience additional challenges managing their diabetes during hospital admissions and after birth. My project will examine how the mother's glucose levels and insulin therapy relate to baby’s growth patterns and birthweight. It will also examine which diabetes technologies help pregnant women to achieve their glucose targets during hospital admissions and after birth. I will perform three studies: firstly, focusing on understanding baby’s growth patterns, secondly on examining mother’s glucose levels during hospital admissions, labour and delivery, and thirdly, during the six months after birth. My project addresses three top priority diabetes pregnancy research questions; (1) use of diabetes technology to improve pregnancy care; (2) women’s experiences and choices surrounding labour and delivery and (3) postnatal care and support.

Since its discovery, the role of neurons in pancreas biology remains controversial. This is in part due to the lack of tools required for directly controlling pancreatic nerves and assessing the effects in living animals. Zebrafish studies are translatable to human development and disease given the high conservation of organs and physiology. I have established assays necessary for live zebrafish analysis of pancreas neurobiology and plan to implement these tools by targeting neurons that produce the galanin neuropeptide. The pancreatic islets are important for producing the hormones that help regulate blood glucose levels. Following the increase or decrease in galanin signals, we will visualize the effects on pancreatic islet formation and activity. The tools developed from these studies will be used to help us understand neural control of pancreas biology (including the regulation of hormone release) under normal and diseased states.

Both obesity and increased blood sugar are important factors in the development of type 2 diabetes (T2D). They are controlled by hormones such as insulin and ghrelin. Ghrelin stimulates food intake, promotes weight gain and inhibits insulin secretion from islets in the pancreas, which in turn leads to higher blood sugar levels. Targeting ghrelin action may therefore be a way of preventing or treating obesity and/or T2D, but so far no useful pharmaceutical blockers of ghrelin have been discovered.

Importantly, a new protein from the liver and small intestine has now been found to counteract the effects of ghrelin. Our initial experiments suggest that this small protein, Liver-Enriched Antimicrobial Peptide-2 (LEAP2), stimulates insulin secretion. Interestingly, this action differs between males and females. Our study will investigate the role of LEAP2 in regulating blood sugar levels, focusing on sex-specific differences and the way this peptide affects pancreatic islet function.

For people with T1D, exercise is beneficial, potentially reducing the progression of diabetes-related complications. Many people (up to 80%) with T1D still release small amounts of insulin together with C-peptide, a molecule involved in the creation of insulin, from the pancreas. This may also help protect against diabetes complications, although exactly how is currently unknown. One possible way is through endothelial progenitor cells (EPCs), which circulate in the blood and repair blood vessels; with T1D associated with having lower numbers of these important cells. We have recently discovered that individuals who no longer produce any insulin/C-peptide are not able to increase the number of EPCs after exercise, compared to those who still produce insulin/C-peptide from the pancreas. We propose exploring how having some ability to still make insulin/C-peptide may influence how well EPCs work in normal and high blood glucose conditions, and whether this works in combination with exercise.