Endocrine Abstracts

Pregnancies affected by GDM commonly result in large-for-gestational-age (LGA) infants, which have an increased risk of developing cardiometabolic complications. The mechanisms responsible are unclear but are associated with altered placental physiology. We have previously reported that miRNAs, including pancreatic specific miR-375, are altered in maternal serum extracellular vesicles (EVs) prior to the onset of LGA, and in term placenta. We assessed maternal pancreatic-derive...

Life on earth is governed by the continuous 24-hour cycle of light and dark. Organisms have adapted to this environment with clear diurnal rhythms in their physiology and metabolism enabling them to anticipate predictable environmental fluctuations over the day and to optimise the timing of relevant biological processes to this cycle. It is of considerable interest that the normal diurnal variation in these processes is lost in the presence of insulin resistance, obesity and d...

Metformin is a first-line therapy for type-2 diabetes mellitus and gestational diabetes mellitus (GDM) which shows significant benefits for maternal health. However, offspring exposed to metformin in-utero have an increased risk of being born small for gestational age and developing cardiometabolic complications in adulthood. The mechanisms responsible are unknown. As fetal growth is dependent on optimal placental function, we assessed whether metformin exposure alter...

Introduction: Measurement of microRNA (miRNA) in aldosterone-producing adenoma (APA) tissue from primary aldosteronism (PA) patients show levels of the miR24-1 cluster miRNAs (i.e. miRNAs 24-1, 27b and 23b) are significantly reduced relative to normal adrenal tissue. Our previous studies also show that miRNA-24 directly targets CYP11B2 (aldosterone synthase) gene expression. Circulating miRNAs released into the bloodstream may be diagnostic biomarkers or signalling mo...

Many cases of hypertension are associated with inappropriately high levels of aldosterone secretion and it has been proposed that microRNAs play a role in this dysregulation. Previously, we showed that microRNAs expressed within the adrenal cortex significantly repress aldosterone production. Furthermore, stimulation of aldosterone secretion by three different means in the H295R cell line – the most commonly-used in vitro model of the human adrenal cortex – ...

Gestational Diabetes Mellitus (GDM) is associated with adverse outcomes, including large-for-gestational age (LGA) babies who are are at greater risk of developing cardiovascular and metabolic diseases in adulthood. The mechanisms responsible for LGA are unclear but it is associated with altered placental development/function. Recent data also shows a link between temporal changes in maternal glucose and LGA; women with GDM that deliver appropriate for gestational age (AGA) in...

It is generally accepted that hepatic responses to α-adrenergic agonists are dependent on the redistribution of intracellular and also extracellular Ca2+. Besides, phenylephrine induces significant K+ flux changes and plasma membrane hyperpolarisation. Earlier it was shown that K+ channel blockers as well as chelating of extracellular Ca2+ with EGTA could inhibit phenylephrine-induced metabolic responses and activation of mitoch...

The AR pathway accumulates myriad genomic and transcriptomic alterations during progression of prostate cancer to a lethal castration-resistant phenotype. The best characterized alterations are point mutations or amplification of the AR gene. More recently, our group had identified structural rearrangements in the AR gene as a novel class of alterations that occur frequently in castration-resistant prostate cancer (CRPC) tissues. AR gene rearrangements are associated with outl...

Aims: Women with gestational diabetes (GDM) who deliver large-for-gestational age (LGA) infants have subtle (1-1.5mM) differences in temporal maternal glucose control detectable by continuous glucose monitoring (CGM), compared to women who deliver appropriate-for-gestational-age (AGA) infants. It is unclear how these subtle changes cause LGA, but LGA has been linked to placental dysfunction. We aimed to develop an ex-vivo human placental model to mimic subtle differences in te...

Background: Gestational diabetes mellitus (GDM) is associated with increased rates of large-for-gestational-age (LGA) or small-for-gestational-age (SGA) infants. Currently, it is not possible to predict which women with GDM are at risk of delivering LGA or SGA infants. Fetuin-A, (α 2-Heremans Schmid glycoprotein; AHSG), a glycoprotein associated with insulin resistance is altered in GDM maternal serum. It is unclear if levels are related to altered fetal growth. This stud...