Drinking three to four cups of coffee a day has been shown to reduce the risk of developing Type 2 diabetes by 25 per cent compared to those who drank one cup or less.
It had been thought caffeine was responsible but this was later discounted as decaffeinated coffee had the same effect.
Now Danish scientists found one of these previously untested compounds cafestol appears to improve cell function and insulin sensitivity in mice.
The discovery could lead to new drugs to treat or even prevent the disease which affects around 3.6 million Britons.
Coffee contains a large number of bioactive substances that can be categorised as alkaloids.
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Previous studies involved filter coffee but the cellulose filter papers trap cafestol so levels are low containing only 0.1 mg.
Instead a cup of Scandinavian boiled coffee contained 6.2 mg, Turkish coffee 4.2 mg, and cafetiere 2.6 mg.
Dr Fredrik Brustad Mellbye of Aarhus University Hospital said: “Coffee contains a large number of bioactive substances that can be categorised as alkaloids.
“The main stimulant in coffee, caffeine, has attracted major interest.
“However, since decaffeinated coffee displays the same inverse association with type 2 diabetes development as caffeinated coffee, it is less likely that all the beneficial effects of coffee are merely or mainly attributed to caffeine.”
In a previous study, Dr Mellbye and colleagues found cafestol increased insulin secretion in pancreatic cells when they were exposed to glucose.
It also increased glucose uptake in muscle cells just as effectively as a commonly prescribed antidiabetic drug.
In the new study, the researchers wanted to see if cafestol would help prevent or delay the onset of Type 2 diabetes in genetically modified mice that becomes obese after birth.
The mice prone to develop Type 2 diabetes were divided into three groups with two given differing doses of cafestol at 1.1mg classed as high or 0.4mg classed as low
After 10 weeks, fasting plasma glucose was 28 to 30 per cent lower in both sets of cafestol-fed mice compared to a control group, which was not given the compound.
Fasting glucagon was 20 per cent lower and insulin sensitivity improved by 42 per cent in the high-cafestol group.
It also increased insulin secretion from isolated islets by 75 to 87 per cent compared to the control group.
Cafestol also didn’t result in hypoglycemia, or low blood sugar, a feared possible side effect of some antidiabetic medications such as insulin and sulfonylureas.
The mice on a high dose also suffered higher levels of “bad” cholesterol and put on weight.
But Dr Mellbye said: “We anticipate that the oral antidiabetic dose in humans will be relatively low and that the antidiabetic benefits will not be outweighed by a small increase in LDL cholesterol.”
He noted the mice were given the equivalent of 11 and 31 cups every day, respectively.
He said: “The present study adds further knowledge about mechanisms of action of bioactive substances in coffee.
“Daily consumption of cafestol can delay the onset of Type 2 diabetes in these mice, and that it is a good candidate for drug development to treat or prevent the disease in humans.”
The study was published in the American Chemical Society’s Journal of Natural Products.