Dr James Bowe

My PhD focused on the hypothalamic regulation of the reproductive system by stress and was primarily an in vivo project that used various techniques including complex surgical procedures (e.g. chronic cannulation of specific brain regions, implantation of telemetry probes).

Since completing my PhD I have worked in diabetes research at King’s College London on projects involving skills including the isolation and maintenance of primary tissues, immunohistochemistry, cell biology transduction cascades, hormone secretion assays and in vivo administration of biologically active substances. This included a DRWF non-clinical fellowship from 2008-2012 which focused on defining the physiological role of kisspeptin in islet function. Kisspeptin is a peptide found, along with its receptor, in a few areas of the human body – including the hypothalamic area of the brain, the placenta and the endocrine pancreas. One important function of kisspeptin in the brain is to control when the process of puberty starts and to regulate subsequent reproductive function, but the function(s) of kisspeptin in the pancreas were unclear.

Following my fellowship I began to establish my own laboratory at King’s College London and my research has developed into the field of pregnancy and gestational diabetes mellitus (GDM), specifically the mechanisms underlying the islet adaptation to pregnancy. Pregnancy presents the maternal metabolism with the problem of providing for the energy requirements of the growing fetus while maintaining fuel homeostasis in the mother. The reversible adaptive changes include a progressive increase in maternal insulin resistance during the last 20 weeks of gestation. In a healthy mother the insulin resistance is countered by increased insulin secretion to maintain normoglycaemia. The increased insulin secretory capacity is met through functional and structural changes in the islets, including an increased β-cell mass. Failure to compensate for the increased metabolic demand in pregnancy leads to the development of glucose intolerance, hyperglycaemia and GDM. Undiagnosed and untreated hyperglycaemia in pregnancy is associated with a range of problems, including preeclampsia, large for gestational age (birth weight>90th centile), birth injury, and neonatal hyperinsulinism and hypoglycaemia. The rapid worldwide increase in the prevalence of type 2 diabetes mellitus (T2DM) is well-documented, but it is less appreciated that the incidence of GDM is also rapidly rising in parallel with the T2DM pandemic. At present the signals regulating the β-cell adaptation to pregnancy are unclear. Prolactin and placental lactogen have been implicated, however are unlikely to explain all of the β-cell adaptive responses. A more complete understanding of the mechanisms involved in β-cell mass during pregnancy would be of obvious benefit for GDM. Through work funded by the Wellcome Trust, the BBSRC, the EFSD and the DRWF we have shown that kisspeptin plays a physiological role in regulating the adaptation of islets to pregnancy and are continuing to further investigate the mechanisms underlying this adaptation and the signals involved. We also have other ongoing projects looking at other aspects of the islet adaptation to pregnancy, such as the effects of depression on islet function.