Investigating the role of the gut in dysfunctional vascular health

A new IPAN project is aiming to explain why a diet high in sugar can lead to insulin resistance and type 2 diabetes.

Associate Professor Michelle Keske is working to discover a new mechanism that links the gut to poor skeletal muscle microvascular blood flow after consumption of a high-sugar meal or drink.

“We know that insulin stimulates microvascular blood flow in skeletal muscle after we eat and drink to help deliver nutrients to the muscle,” Associate Professor Keske explained.

“Poor blood flow in the skeletal muscle after eating and drinking is a hallmark feature of insulin resistance and type 2 diabetes.

“However, our new research has shown that this vascular impairment can also occur in healthy people if they consume a meal or a drink that contains too much sugar.”

Associate Professor Keske’s team recently completed a human study showing that the route of sugar administration, rather than the amount of sugar in the blood, determines whether muscle microvascular blood flow is impaired or enhanced.

“We found that when sugar is administered orally muscle microvascular blood flow is impaired, whereas when sugar is administered intravenously this enhances microvascular blow flow,” she explained.

“Given intravenous infusion bypasses the gut, our data provides evidence for the first time that something is being released from the gut upon oral consumption of high amounts of sugar that leads to impairment of muscle microvascular blood flow.”

This project, funded through a Diabetes Australia Research Program grant, will analyse blood samples to identify what factors are being released from the gut.

Associate Professor Keske said that while there is considerable evidence linking microvascular dysfunction to development of insulin resistance and type 2 diabetes, very little was known about distinct sugar-related mechanisms that lead to microvascular complications in muscle.

“This work will provide new insight into why diets high in sugar over the long-term are detrimental to vascular health, and subsequently, contribute to the increased risk of insulin resistance and pre-diabetes,” she said.

“The link between the gut and the microcirculation in skeletal muscle as a potential cause of vascular insulin resistance is a completely new research area which has significant clinical implications– in other words, we need to consider the gut as an important contributor to insulin resistance and pre-diabetes.”

This research could potentially help inform new treatments to stop the decline in vascular health for people with insulin resistance, pre-diabetes and type 2 diabetes.