Compensatory β-cell mass expansion

Pancreatic β-cells, located within the islets of Langerhans, are key players in the control of blood glucose homeostasis. The amount of insulin secreted by these cells is precisely adjusted to avoid hypoor hyperglycaemic episodes and prevent the appearance of diabetes mellitus. Pregnancy and obesity are associated with diminished insulin sensitivity of target tissues and a consequent rise in insulin needs. The increased insulin demand is normally compensated by expansion of β-cells and improvement in their secretory activity. A better understanding of these adaptive events could open new therapeutic perspectives for prevention and/or treatment of type 2 and gestational diabetes. MicroRNAs are gene expression regulators that reduce translation and/or stability of target mRNAs by binding to their 3'-untranslated regions. These tiny RNA molecules govern different physiological and pathological processes and participate to the regulation of β-cell functions. We recently provided evidence that microRNAs contribute to compensatory β-cell mass expansion in response to insulin resistance associated with pregnancy and obesity. We found that in rat islets β-cell expansion during pregnancy is coupled to changes in the level of some microRNAs. These changes were reproduced in dissociated rat islet cells by transfecting oligonucleotides that either mimic or block each microRNA. This revealed that knockdown of miR-338-3p, a microRNA downregulated in the islets of pregnant rats, does not interfere with the secretory properties of β-cells, but boosts their proliferation and improves their survival under pro-apoptotic conditions. Interestingly, the level of miR-338-3p is also diminished Compensatory β-cell mass expansion A big role for a tiny actor