Why Some Diabetes Meds Work With Mice, But Not Humans

The reasons that some pharmaceutical answers for diabetes do well in mice-based studies but then fail when human trials are given have been ambiguous and largely unexplained. These are often chalked up to "differences" rather than being further researched. A new study has shed light on those "differences" and why they can mean a viable medication in mice doesn't translate to humans.

Researchers from Lund University in Sweden and King's College London have discovered new differences between humans and mice that explain why many diabetic drugs do well in mice trials and fail in human ones. Their findings are core to why diabetic drugs in particular are so often not translating from mice to man.

G protein-coupled receptors (GPCRs) in insulin-producing beta cells in the pancreas are not the same in mice as they are in humans.

GPCRs are found on the surfaces of many cells and are meant to receive chemical messages from G proteins. Each GPCR is tuned to a different G protein, with about 1,000 in all being found in most people. Not all GPCRs are tuned for insulin or diabetes-related issues, but many are. Because of the variety of GPCRs in the body, many pharmaceuticals target them to make changes in how we react to various things in order to treat disease or side-effects.

GPCR-targeted drugs for type 2 diabetes, however, have had little success. Now we may know why. The European researchers found that the receptors being targeted for type 2 diabetic treatments are not the same in mice as they are in people. The study didn't find that the differences exist, as that had previously been explored in papers explaining the failures of translation. The new study does, however, clearly define some of those differences.

The researchers also found some promising similarities that could resolve some of those translation problems from mouse treatments to human ones. Also important, it shows why many lines of study into treatments will not be effective in humans despite their apparent effectiveness in mice. This will help narrow study and remove many studies that are likely to fail when reaching human trial.

The researchers mapped several GPCRs that are similar in both mice and humans and thus opened new scope for research. This will give a better idea to scientists looking for answers and give them a roadmap towards potential new medications for type 2 diabetes.

Source: ScienceAlert.com

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