Endocrine Abstracts

Hyperglycaemia drives microvascular damage in type 2 diabetes (T2D) and while this link is well established, its timing and causality are not fully understood. Using non-invasive contrast-enhanced ultrasound (CEUS) imaging and post-processing super-resolution ultrasound (SRUS) to generate high-resolution structural and dynamic maps of the microvasculature in digestive and associated organs, we aimed to study the microvascular changes in T2D. Male Tally Ho (TH) mice develop diabetes spontaneously around 10 weeks old, allowing us to monitor their microvascular health throughout the onset of T2D. Subsequently, we treated diabetic TH mice with glucagon-like-peptide2 analogue Teduglutide (0.3 mg/kg) with the aim of correcting the observed decrease in blood velocity (BV). Our results showed a significant negative correlation between fasted glycaemic levels and BV in the microvasculature of the duodenal wall (R²=0.1896, P = 0.0001), pancreas (R²=0.1527, P = 0.0002) and kidney (R²=0.0626, P = 0.0181), but not liver (R²=0.0251, P = 0.1718). There was a significant reduction in microvascular BV in the duodenal wall and the pancreas between heathy mice and diabetic mice (P = 0.0011 and P = 0.0019, respectively). Chronic 14-day twice-daily injections of Teduglutide resulted in a trend towards increased BV in the duodenum and liver compared to the mice given a vehicle control. These results suggest that microvascular changes occur before frank diabetes and that hyperglycaemia may be driving both islet damage and impaired nutrient sensing through microvascular damage. BV reduction in digestive organs may have important endocrine consequences beyond T2D, especially in appetite and energy homeostatic pathways. Preliminary results seem to suggest that chronic Teduglutide administration may correct this change in BV in the duodenum and liver, but further work is required. More broadly, these results illustrate the use of CEUS and SRUS as novel tools to non-invasively and longitudinally visualise microvascular beds, providing insight into mechanisms of disease and potential drug targets.