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Metabolic regulation in diabetes

Millions of people suffer from diabetes worldwide. Understanding how the disease manifests at the molecular level is central to the design of novel interventions.
Metabolic regulation in diabetes
Type 2 diabetes is an autoimmune metabolic disorder that incurs a great cost for its clinical management. Before the onset of disease, patients suffer from a condition known as insulin resistance, where insulin cannot maintain blood sugar levels at physiological levels. This progressively leads to the production of insufficient amounts of insulin and hence the outbreak of diabetes.

It is now well established that signalling downstream of the insulin receptor is deregulated in type 2 diabetes and also plays a pivotal role in the pathogenesis of insulin resistance. As a result, understanding the regulation of glucose homeostasis and insulin signalling at the molecular level can have important clinical projections.

Scientists on the EU-funded CUL7 AND DIABETES (Role of the Cullin7 E3 ubiquitin ligase in insulin signaling and diabetes) project focused on Cullin ring E3 ubiquitin ligase 7 (CRL7), a molecular complex that contains CUL7, a previously identified regulator of insulin signalling. The aim was to delineate the role of CRL7 in the cellular insulin response and insulin resistance.

In vitro depletion of CUL7 in myotubes led to an increased activation of insulin signalling and cellular glucose uptake. These observations were concomitant with a reduced capacity of these cells to execute insulin-induced degradation of insulin receptor substrate 1. Mice heterozygous for Cul7 displayed enhanced insulin sensitivity and plasma glucose clearance, underscoring a role for CRL7 in metabolism.

Overall, delineating the metabolic functions of CRL7 will pave the way to development of novel therapeutic strategies that modulate insulin function.

Related information


Metabolic, diabetes, insulin resistance, insulin signalling, CUL7, CRL7
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