Endocrine Abstracts

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a new class of oral anti-diabetic medications that improve glycaemia by reducing the amount of glucose being absorbed in the kidneys. SGLT2 inhibitors have been proven to improve blood pressure, cardiovascular health and kidney disease. Despite their beneficial clinical effects, their exact mechanism of action is not fully explored. The aim of this project was to investigate the effect of SGLT2 ...

Obesity, a complex metabolic disorder characterised by excessive adipose tissue accumulation, is associated with numerous health complications. This study aimed to investigate the molecular mechanisms underlying obesity, focusing on the role of hypoxia-inducible factor 1 alpha (HIF1α). Our findings establish a novel link between HIF1α and the pathogenesis of obesity-related conditions. We uncovered a connection between HIF1α and diabetic neuropathy, a prevalent ...

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...

Brown adipose tissue (BAT) is a therapeutic target for obesity and associated metabolic diseases, due to its role in non-shivering thermogenesis. BAT activation is mediated through sympathetic stimulation, but parasympathetic regulation of human BAT has not been demonstrated previously. We undertook RNA sequencing of human white and brown primary adipocytes to identify novel pathways regulating BAT. CHRM2 (encoding the muscarinic acetylcholine receptor 2) was the most differen...

In utero exposure to maternal obesity programs an increased risk of obesity. Animal models have shown that offspring obesity is often preceded by increased food intake, however, the mechanisms that mediate these changes are not understood. Using a mouse model of maternal diet-induced obesity we observed increased intake specifically of a high-fat pellet in adult offspring of obese mothers. Through small RNA sequencing, we identified programmed overexpression of miR-505-5p in t...

Background: Carbohydrate-restricted diets in type 1 diabetes mellitus (T1DM) are highly controversial. A commonly held concern is that a low carbohydrate diet may more readily result in conversion to diabetic ketoacidosis – one of the most severe complications of poorly managed T1DM. Of note, there is no clear evidence for this phenomenon. We evaluated metabolic profiles in patients with T1DM who had self-selected carbohydrate-restricted diets.<p clas...