Endogenous insulin mediates dynamic coordination between pancreatic cancer and systemic metabolism
Pancreatic ductal adenocarcinoma (PDAC) is commonly associated with obesity, diabetes, and cachexia. The pancreatic anabolic hormone, insulin, is implicated in each of these metabolic diseases, but how insulin levels affect tumor growth and relevant host physiological factors, was unclear. To address this, we transplanted orthotopic PDAC patient-derived organoids into mice consuming a…
Pancreatic ductal adenocarcinoma (PDAC) is often linked to obesity, diabetes, and cachexia, all of which are influenced by insulin, a pancreatic hormone. However, the extent to which insulin affects tumor growth and host physiological factors remained unclear. To shed light on this, researchers implanted PDAC patient-derived organoids into mice fed a high-fat diet (HFD), which leads to increased insulin levels in tumors compared to circulation.
When insulin levels were genetically reduced, PDAC growth was curtailed, especially in HFD-fed mature male mice.
The presence of pancreatic tumors in these mice resulted in increased glucose clearance and limited dietary-induced increases in insulin, weight, and fat mass. Interestingly, tumor growth in mice consuming normal chow, rather than the HFD, was associated with declining circulating insulin levels and reductions in fat and muscle mass. The findings offer fresh insights into the intricate, insulin-driven relationship between PDAC and systemic metabolism, which contributes to cancer-associated metabolic dysfunction.
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