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Professors from Denmark and Canada strike up collaboration to investigate the relationship between antipsychotic medication and rapid blood sugar rises. The study will be carried out on so-called knock-out mice initially, but human studies are also envisaged.

Second-generation antipsychotics (SGAs) are used to treat schizophrenia, but they are also seeing increasing use as an off-label treatment for conditions such as anxiety, bipolar disorder and depression. The side effects of SGA use have usually been related to weight gain and associated metabolic complications, but new research has shown that SGAs can cause blood glucose concentration to rise after ingestion.

The development of SGA-induced hyperglycaemia has been shown to be linked to increased glucose production in the liver and impaired insulin sensitivity, which increases the risk of developing type 2 diabetes.

‘Our hypothesis is that a reduction of the energy-sensitive enzyme 5'-AMP-activated protein kinase (AMPK) in the skeletal musculature will increase SGA-induced hyperglycaemia, while an activation of AMPK will attenuate the effect of SGAs on blood sugar’, explains Professor David Wright of Canada. For the next two years, he will be Visiting Professor in the Department of Molecular Physiology at the University of Copenhagen.

The research will make use of genetically engineered mice, known as knock-out mice, developed at the University of Copenhagen’s Section for Molecular Physiology, where Professor Jørgen Wojtaszewski works; he and Professor Henriette Pilegaard will together be David Wright’s hosts and closest collaborators.

‘We have developed an inducible, muscle-specific AMPK knock-out mouse. It will be an ideal model for the studies and for research into the relationship between the use of antipsychotics and metabolic side effects. With this research collaboration, we will strengthen the links between the University of Copenhagen and the University of Guelph in Canada, and we will be able to exchange both research and researchers across sectors’, says Professor Jørgen Wojtaszewski, who expects the work with David Wright to result in a joint publication later on.

The foundation for a human clinical study

David Wright, who has received DKK 150,000 from the Danish Diabetes Academy, is looking forward to his visit and emphasizes that the results may lead to new clinical studies and possible tests on humans.

‘Meetings will be held between clinical and basic researchers from Canada and Denmark with a view to laying the foundation for a clinical study. The aim of such a clinical study will be to clarify the connection between AMPK mutations and the development of disrupted glucose metabolism in SGA therapy’, says David Wright.

By Pernille Fløjstrup Andersen, Communications Officer, and Tore Christiansen, Managing Director, DDA

Facts

Dr David Wright, Professor, University of Guelph, Guelph, Ontario, Canada

Has been awarded DKK 150,000 by the Danish Diabetes Academy.

Title: Targeting Skeletal Muscle AMPK to Offset the Acute Hyperglycemic Effects of Antipsychotic Drugs

Research centre: Section for Molecular Physiology, University of Copenhagen

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Contact Danish Diabetes Academy

Managing Director Tore Christiansen

Email: tore.christiansen@rsyd.dk

Phone: +45 2964 6764