Metabolism and Vascular Research - The Premilovac Group

Our research aims to understand the mechanisms that regulate blood flow and hence metabolism in organs such as skeletal muscles and the brain in health, obesity, insulin resistance and type 2 diabetes.

The primary goal of our research is to better understand the relationship between blood flow and metabolism in organs such as skeletal muscle, adipose tissue and the brain. To do this, we study how blood flow and metabolism are linked in health to enable normal function and how these processes are altered in disease states including obesity, type 2 diabetes, ischaemic stroke, dementia, diabetic retinopathy, and peripheral neuropathy. Our research group primarily uses animal models to investigate the complex interplay between blood vessels and metabolism in health and disease. We are experts in many techniques including real-time blood flow imaging using ultrasound, biochemistry, pharmacology, anatomical assessment using histology and microscopy, as well as sophisticated methods for assessment of metabolism such as glucose tolerance testing, radioactive glucose tracing and the insulin clamp technique.

Expertise

  • Obesity, insulin resistance and type 2 diabetes
  • Cerebral blood flow and stroke
  • Insulin signalling and actions
  • Insulin action in the brain
  • Skeletal muscle blood flow and glucose metabolism
  • Microvascular and capillary blood flow imaging
  • Contrast enhanced ultrasound
  • Exercise physiology

Projects

How does insulin resistance alter brain vascular function and metabolism? Can medications like Ozempic restore normal brain vascular function to prevent cognitive decline?

Insulin has a number of effects in the body to regulate blood glucose levels. Insulin resistance develops when the body’s cells stop responding to insulin normally and insulin resistance is linked with increased risk of brain disorders such as stroke and dementia. This project aims to understand how insulin works to regulate regional cerebrovascular blood flow and glucose uptake, how this is lost in disease states such as insulin resistance and type 2 diabetes and whether drugs like Ozempic can restore normal insulin actions in the brain.

Using ultrasound to measure brain blood flow in real-time after stroke.

Our research has developed ultrasound-mediated assessment of blood flow in the brain before, during and after ishcaemic stroke. This project aims to understand how blood flow regulation is altered after ischaemic stroke and how this correlates with brain damage. In addition, we aim to define a vascular therapy to improve blood vessel health and function after ischaemic stroke to enhance brain recovery.

Is air pollution a trigger for development of insulin resistance?

Urban air pollution is increasingly linked with development of cardiovascular disease and type 2 diabetes. This project aims to determine whether exposure to a common urban air pollutant, diesel exhaust, leads to development of insulin resistance in experimental rodents.

Can we use non-invasive ultrasound to increase drug delivery to the brain?

Delivering drugs to the brain to treat neurological diseases is difficult for two reasons. the first is the presence of the blood brain barrier that prevents entry of drugs into the brain. The second is the off-target effects of drugs on other organs in the body. We have developed a way to trap drugs within microbubbles to enable microbubbles to act as tiny capsules within the blood. This project aims to determine whether we can target delivery of drugs to the brain in neurological disease by using ultrasound to crack open these tiny microbubbles capsules.

Do pericytes regulate capillary blood flow in skeletal muscles?

Appropriate control of blood flow in skeletal muscles is an important determinant of exercise performance and glucose uptake in response to insulin. This project aims to understand the functional roles capillary bound pericytes play in the regulation of blood flow in skeletal muscles at rest, during exercise and in metabolic diseases such as insulin resistance and type 2 diabetes.

Key Publications

  1. Southam K, de Sousa C, Daniel A, Taylor BV, Foa L, Premilovac D. Development and characterisation of a rat model that exhibits both metabolic dysfunction and neurodegeneration seen in type 2 diabetes. The Journal of Physiology. 2022 Apr;600(7):1611-30.
  2. Premilovac D, Blackwood SJ, Ramsay CJ, Keske MA, Howells DW, Sutherland BA. Transcranial contrast-enhanced ultrasound in the rat brain reveals substantial hyperperfusion acutely post-stroke. Journal of Cerebral Blood Flow and Metabolism. 2020 May;40(5):939-53.
  3. Keske MA, Premilovac D, Bradley EA, Dwyer RM, Richards SM, Rattigan S. Muscle microvascular blood flow responses in insulin resistance and ageing. The Journal of physiology. 2016 Apr 15;594(8):2223-31.
  4. Attrill E, Ramsay C, Ross R, Richards S, Sutherland BA, Keske MA, Eringa E, Premilovac D. Metabolic‐vascular coupling in skeletal muscle: A potential role for capillary pericytes?. Clinical and Experimental Pharmacology and Physiology. 2020 Mar;47(3):520-8.
  5. Premilovac D, Attrill E, Rattigan S, Richards SM, Kim J, Keske MA. Acute, local infusion of angiotensin II impairs microvascular and metabolic insulin sensitivity in skeletal muscle. Cardiovascular research. 2019 Mar 1;115(3):590-601.

Group Leader(s)

Affiliation

Biomedical Sciences

School of Medicine

Contact

Email: Dino.Premilovac@utas.edu.au

Group members

  • Dr Dino Premilovac
  • AProf Renee Ross
  • Sophie Mayne (PhD)
  • George Poneris (PhD)
  • Ella Matson (PhD)
  • Isabella Hippel (honours)