Fresh evidence reveals the gut may play a role in diabetes risk and poor vascular health  

An IPAN research project has uncovered a link between the gut and insulin resistance.  

New research has shown that consuming a high amount of sugar triggers a response in the gut that leads to impairment of muscle microvascular blood flow (our smallest blood vessels).  

Professor Michelle Keske’s team completed a human study showing that the way sugar enters the bloodstream, 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 given orally via a sugary drink, muscle microvascular blood flow is impaired, whereas when sugar is administered intravenously (i.e. via a vein) this enhances microvascular blood flow,” she explained.  

“Given sugar delivered via a vein bypasses the stomach, our data provides evidence for the first time that something is being released from the stomach when high amounts of sugar are consumed that leads to impairment of muscle microvascular blood flow.”  

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

 “We know that insulin stimulates microvascular blood flow in skeletal muscle after we eat and drink to help deliver nutrients to the muscle,” 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 in muscle can also occur in healthy people if they consume a meal or a drink that contains too much sugar. 

“This work provides 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.  

“The link between the gut and the smallest blood vessels 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.”  

The research team at the Institute for Physical Activity and Nutrition (IPAN), Deakin University, examined several hormones found in the plasma samples released from the gut and identified gastric inhibitory peptide (GIP), as a potential cause of the reduced blood flow response after consuming the sugary drink.    

Prof Keske said identifying the GIP hormone as a potential driver of impaired muscle microvascular flow following a high-sugar drink was important because it would:  

  • provide a new link explaining why diets high in sugar lead to vascular dysfunction, leading to an increased risk of developing insulin resistance and pre-diabetes; and  
  • inform new treatment strategies targeting gut-derived factors to prevent the decline in vascular health in people with insulin resistance, pre-diabetes and type 2 diabetes. 

The project was funded through a Diabetes Australia Research Program grant. 


Further information: 

  • This work was published in the Journal of Physiology (Q1 journal, impact factor 6.3):  

K.M. Roberts‐Thomson, L. Parker, A.C. Betik, G.D. Wadley, P.A. Della Gatta, T.H. Marwick and M.A. Keske. Oral and intravenous glucose administration elicit opposing microvascular blood flow responses in skeletal muscle of healthy people: role of incretins. The Journal of Physiology. 2022;600(7):1667-81.  Doi: 10.1113/JP282428. 

  • The publication was selected as a Journal of Physiology Editor’s top choice, and led to the following Perspective article and Journal Club articles:  
  1. Andrea Tamariz-Ellemann, Hannah G. Caldwell and Lasse Gliemann. Gastric inhibitory polypeptide as the new candidate for the interaction of skeletal muscle blood flow and glucose disposal. The Journal of Physiology; Perspectives. 2022;600(7): 1593-1595.  
  2. Jeremy N. Cohen and Jennifer A. Wilkinson. Sweet release-intravenous, not oral, glucose administration increases microvascular blood flow. The Journal of Physiology; Journal Club. 2022;600(8): 1519-1820.