Adaptation of pancreatic islets to pregnancy: a role for kisspeptin

In 2013, more than 60% of deaths and a massive burden of disease in children under the age of five years in sub-Saharan Africa were due to infections. However, individual responses to infection are highly variable and risk factors predisposing children to death and disease remain poorly understood. Potentially life-saving interventions that can reduce or remove risk factors may have been overlooked. A plausible risk factor is chronic infection with human schistosomes. Infection with these parasites causes schistosomiasis, the second most important parasitic disease in sub-Saharan Africa. In addition to direct local and systemic pathological effects, schistosome infection also exacerbates pathology and alters overall host immune phenotype and physiology. It is therefore surprising that the indirect, long-term effects of schistosome infection on host health remain un-investigated.

This project aims to optimise novel and innovative systems biology assays for assessing host health status including infection, clinical presentation of disease and response to vaccination. T
he project will act as a pilot for a larger study combining epidemiological investigations of schistosome infection in young children as a risk factor for subsequent death or disease due to other causes with investigations of altered progrOur preliminary data support a novel and important role for placental kisspeptin in beta-cell adaptations for the metabolic demands of pregnancy. This project will test the hypothesis that circulating kisspeptin in pregnancy acts as a placental signal to inform beta-cells of the pregnancy and to mediate adaptive responses to pregnancy in the cells. Failure of this system in pregnancy may reduce or prevent the pregnant woman’s adaptive responses to increased metabolic load and peripheral insulin resistance, leading to the development of gestational diabetes.

The hypothesis will be addressed through two main experimental objectives. We will define the role of placental kisspeptin in enhancing beta-cell insulin secretory responses to compensate for pregnancy-induced insulin resistance and investigate the role of kisspeptin in beta-cell proliferation leading to increased islet mass during pregnancy.