Kei Sakamoto receives 2026 Diabetes Prize for uncovering what still works when insulin falters

Professor Kei Sakamoto of the University of Copenhagen has been awarded the 2026 EASD–Novo Nordisk Foundation Diabetes Prize for Excellence. His research has helped uncover how working muscle can still take up glucose when insulin signalling is impaired, and revealed an important part of how metformin – one of the world’s most widely used medicines for type 2 diabetes – lowers blood glucose.

In type 2 diabetes, insulin’s message to muscle becomes weaker, making it harder to clear glucose from the blood. Yet contracting muscles can still take up glucose through other molecular routes – a paradox that has shaped much of Sakamoto’s research.

“Sometimes we focus too much on what is going wrong,” says Kei Sakamoto, Professor at the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen. “The problems can be too complex and diverse. Instead, I ask: when there are defects, what still works?”

His discoveries have helped establish the LKB1–AMPK pathway as an important signalling route through which working muscle senses energy demand and increases glucose uptake without relying on insulin.

He has also shown how molecules produced during metabolic reactions within cells can act as signals, including through an important mechanism by which metformin reduces blood glucose levels through restraining liver´s production of new glucose.

The prize is accompanied by DKK 6 million (€780,000), comprising DKK 1 million as a personal award and DKK 5 million for research.

“The previous recipients represent major discoveries and important contributions to patient care,” Sakamoto says. “In that context, receiving this prize is a great honour. I feel overwhelmed by the recognition.”

“Kei Sakamoto has made fundamental contributions to our understanding of how muscle and liver regulate glucose metabolism. His work has shown how muscle can use alternative signalling routes when insulin signalling is impaired, how metabolites themselves can regulate key metabolic enzymes, and why AMPK must be targeted with precision. Together, these discoveries have reshaped important questions in diabetes research,” says Francesco Giorgino, President of the European Association for the Study of Diabetes (EASD).

Exercise can take another route

Sakamoto's search for those alternative routes began long before he became a molecular biologist. He studied English and communication in Japan and worked for a life insurance company, while also becoming an aerobics instructor and competitor, finishing fifth in the Japanese national championships.

Some people in his classes had type 2 diabetes and had been advised to exercise to control their blood glucose.

His earlier interest in communication later became a way of thinking about biology itself.

“Humans use languages to communicate, and cells also have languages,” Sakamoto says. “You need to understand the language and the grammar to understand the context.”

That curiosity led him to study exercise physiology and eventually to Laurie Goodyear’s laboratory at the Joslin Diabetes Center in Boston, where the question became more specific: exercise could lower blood glucose even when insulin signalling was impaired.

“Even when insulin does not work properly, exercise still works,” Sakamoto says. “It can bypass part of the defect and use a different communication network to take glucose up from the blood.”

One important candidate was AMPK – an energy-sensing enzyme that helps cells bring in and use more fuel when energy runs low.

Sakamoto subsequently joined Dario Alessi’s laboratory in Dundee, where Alessi and colleagues had identified LKB1 as a possible regulator of AMPK.

In mice lacking LKB1 specifically in muscle, contraction produced dramatically less AMPK activity and contraction-stimulated glucose uptake was markedly reduced, while the response to insulin remained intact. The work provided genetic evidence that LKB1 is an important regulator of AMPK and helped explain how working muscle can still take up glucose when insulin signalling is impaired.

Metformin still worked after its supposed switch was removed

The LKB1 experiments reinforced a principle in Sakamoto’s research: a convincing molecular explanation must survive a direct test in living tissue.

Metformin is one of the most widely used treatments for type 2 diabetes, yet important parts of how it works remain unresolved. Because the drug can lower cellular energy and activate AMPK, researchers proposed that AMPK helped suppress glucose production by the liver.

But when researchers removed AMPK from the liver, metformin still lowered blood glucose.

“That was very surprising,” Sakamoto says. “The glucose-lowering effect was essentially normal even without AMPK in the liver.”

Sakamoto and colleagues investigated another possibility. When cellular energy falls, a molecule called AMP rises and can slow FBP1, an enzyme the liver needs to make glucose.

His group altered FBP1 so that it still worked but responded much less to AMP. In these animals, metformin's immediate glucose-lowering effect was substantially weakened.

The experiments provided evidence that metformin partly works through AMP and FBP1, although Sakamoto emphasises that this mechanism does not explain all of the drug’s effects.

The metabolic master switch came with a catch

AMPK once looked like something close to a metabolic master switch: activating it might reproduce some of exercise’s metabolic benefits. But AMPK exists in several forms across different tissues, and broadly activating it has produced both metabolic benefits and unwanted effects in experimental studies.

The challenge is therefore to activate the right form, in the right tissue, and for the right amount of time.

“Our body is complex, with different layers of switching systems,” Sakamoto says. “We do not rely on a single molecule to control something as fundamental as our metabolism.”

His current research includes early-stage approaches designed to activate AMPK more selectively, including strategies to target AMPK activation preferentially to the liver.

This brings Sakamoto back to the question that has guided much of his research: when one route fails, what still works – and can scientists learn enough of the cell’s “language” to use those alternatives without disturbing metabolism elsewhere?

About the prize

Established in 2015, the EASD–Novo Nordisk Foundation Diabetes Prize for Excellence recognises outstanding contributions to diabetes research. The recipient is selected by a prize committee appointed by EASD, while the Novo Nordisk Foundation provides the prize funding.

Professor Kei Sakamoto will deliver his prize lecture on 30 September 2026 at the 62nd EASD Annual Meeting in Milan (EASD).