Role of apolipoprotein CIII in human islet function and survival and relation to comorbidities

Based on our data on apolipoprotein CIII (apoCIII) in animal models of type-2 diabetes (T2D) the objectives of this project is to investigate the role of apoCIII in human islets.

Furthermore, as T2D increases the risk for neurodegenerative disorders, we will clarify if apoCIII is present in the brain and if there occur changes in the levels under conditions of insulin resistance.

Human islet function  will be evaluated in vitro by  hormone release and integrated [Ca2+]i oscillations, b-cell survival, and cytokine production in islets exposed to low and high [apoCIII].For in vivo studies  the approach of transplanting human islet into the anterior chamber of the eye of immune deficient mice will be used.

This allows noninvasive and longitudinal studies of vascularization, innervation, immune responses and apoptosis. We will further assess the effects of manipulating the concentration of apoCIII with siRNAs.

Regarding the brain apoCIII will be determined in commercialized tissue scan arrays from human brains and fresh frozen brains from mice.

We will explore whether diet-induced obesity and T2D, as well as apoCIII lowering treatments, changes the levels of apoCIII in the brain. The methods that are going to be used are already up and running and the expected time for this project is 4-years.

It is important to clarify whether apoCIII has a role linking metabolic diseases with neuronal function as this can identify more specific targets for treatment.