A recent study has shed new light on the mechanisms of obesity-induced diabetes, revealing that stress hormones, rather than impaired insulin signalling, may be the primary factor behind the disease. This discovery could transform future treatments.
Led by Christoph Buettner, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA, the study investigated the role of the sympathetic nervous system in obesity-related diabetes. The researchers found that overeating triggers a rapid increase in norepinephrine, a key stress hormone. This, in turn, over activates the sympathetic nervous system, which counters insulin’s effects despite cellular insulin signalling remaining functional. In essence, while insulin acts to lower blood glucose, stress hormones work oppositely, raising blood glucose and lipid levels. This dynamic results in insulin resistance, where insulin’s ability to reduce blood sugar is diminished despite the hormone still functioning properly at a cellular level.
To explore this further, researchers developed genetically engineered mice incapable of producing stress hormones outside the brain. When these mice were fed a high-fat, high-sugar diet, they did not develop metabolic diseases, even though they became obese. The researchers highlighted that it wasn’t the caloric intake or weight gain itself, but rather the absence of heightened stress hormones that protected these mice from diabetes.
Buettner remarked that this mechanism could explain why certain stresses (financial, marital, or even physical stress) can exacerbate diabetes, particularly in individuals who are obese. The research suggests that obesity and stress might converge through similar pathways to increase the risk of metabolic disease.
The findings open the possibility of new treatments that target catecholamines, the stress-related hormones, as a way to manage or prevent diabetes. Although some blood pressure medications target these hormones, they have not shown significant benefits in diabetes, possibly due to their broader impact on brain and body functions. Future human studies are planned to confirm these findings and investigate their potential for managing various forms of diabetes.
Reference
Sakamoto et al. Overnutrition causes insulin resistance and metabolic disorder through increased sympathetic nervous system activity. Cell Metab. 2024;DOI:10.1016/j.cmet.2024.09.012.
