P5 Direct effect of adipokines and batokines from white and brown adipocytes on islet gene expression

Abstract

Background: The association of type 2 diabetes (T2D) with other cardiovascular risk factors such as overweight/obesity promotes the development of endocrine-metabolic dysfunction. The direct effect produced by adipokines released by white adipocytes (WA) of visceral adipose tissue and batokines released by brown (BA) and beige adipocytes (beige A) on islet cell mass/function is not clear.

Aim: To demonstrate the possible direct effect of metabolites, adipokines and batokines on islet cell function/mass markers, inflammatory response and intracellular insulin mediators.

Materials and methods: pancreas and visceral and interscapular adipose tissues (VAT and IAT, respectively) were removed from normal Wistar rats and digested with collagenase (isolation of islets and adipocytes). Adipocyte phenotype of specific markers expressed in WA (UCP-2 and Wdnm-1); BA (UCP-1 and Cidea) and beige A (TMEM-26) was verified by RT-qPCR. WA and BA were incubated 1h in KRB medium to obtain the corresponding conditioned media (CM-WA and CM-BA). CMs were used individually or in combination (1: 1) as islet incubation media in presence of 16.6mM glucose. Afterall, islet total RNA was isolated and gene expression level of apoptosis´, insulin signaling and inflammatory response markers was study by RT-qPCR.

Results: Identification of specific phenotypic markers allowed us to determine that WA were located in VAT, BA in IAT and beige A in both adipose tissues studied. Islets incubated in presence of CM-WA and CM-BA significantly increased (p <0.05) insulin gene expression and some components of its signaling pathway. While CM-WA increased (p <0.05) the expression of apoptosis markers (Caspase3) and the inflammatory response (TNF-α and IL-1β), CM-BA decreased it. The mix of CMs enhanced some effects and neutralized others.

Conclusions: Adipokines and batokines have direct effects on islet function and survival, some of them are synergistic and others antagonistic. While adipokines would show a negative effect, batokines would induce a protective effect on beta cell function and mass. It could be necessary to identify individual factors responsible for these effects for the development of future therapeutic strategies for the treatment and prevention of type 2 diabetes.