Insulin signalling controls gene reading in kidney cells
Kidney cells that cannot process insulin properly lose more than their metabolism. They also lose the ability to read genes correctly. That is a new insight into how insulin sensitivity contributes to long-term organ health.
Podocytes are specialised cells in the kidney’s glomeruli, its filtration units. They are responsible for preventing proteins in the blood from being lost in urine. When podocytes are damaged, the result is kidney disease and, over time, kidney failure.
In this study, published in eLife, mice were genetically modified so that their podocytes lacked both the insulin receptor and the IGF1 receptor. This combination quickly led to serious kidney damage, including elevated protein levels in the urine (albuminuria) and scarring of the glomeruli. But the most striking finding was what went wrong at the molecular level. The study showed that the spliceosome, the cellular machinery that cuts and splices RNA before it is translated into protein, was severely disrupted.
RNA processing as a new vulnerability
The spliceosome, the molecular machine that edits RNA so that the correct gene segments are translated, turned out to depend on insulin signalling to function properly. Without that signal, widespread intron retention occurred: segments of RNA that are normally removed stayed in place, causing defective proteins to be made or no protein at all. This mechanism had not previously been described in podocytes.
From an aging biology perspective, this is noteworthy. Insulin resistance increases with age and is associated with declining kidney function. If insulin signalling controls not just metabolism but also RNA processing in kidney cells, it raises new questions about how metabolic aging drives kidney damage.
Relevance for type 2 diabetes and aging
Kidney damage is one of the most common complications of type 2 diabetes, a condition centred on insulin resistance. This study provides a new mechanistic lead, though it involves a mouse model and findings have not yet been confirmed in humans. Whether modulating insulin signalling in the kidney could ultimately prevent organ damage requires further investigation.
Search terms to explore further: insulin resistance podocyte kidney damage, spliceosome RNA processing cellular aging, IGF1 signalling gene expression organ function