MicroRNAs and the functional β cell mass: For better or worse

Abstract

Insulin secretion from pancreatic β-cells plays a central role in the control of blood glucose levels. The amount of insulin released by β-cells is precisely adjusted to match the organism requirements. A number of conditions occurring during life, including pregnancy and obesity, can result in a decrease in the sensitivity of insulin target tissues and in the consequent rise in the insulin needs. To preserve glucose homeostasis, the augmented insulin demand requires a compensatory expansion of the mass of pancreatic β-cells and an increase in their secretory activity. This compensatory process is known to be accompanied by modifications in β-cell gene expression but the molecular mechanisms underlying this phenomenon are still poorly understood. Emerging evidence indicate that at least part of these compensatory events may be orchestrated by changes in the level of a novel class of gene regulators, the microRNAs.Indeed, several of these small non-coding RNAs have either positive or negative impacts on β-cell proliferation and survival. The studies reviewed in this paper suggest that the balance between the actions of these two groups of microRNAs with opposing functional effects determines whether β-cells expand sufficiently to maintain blood glucose levels in the normal range or fail to meet the insulin demand with a consequent progression toward diabetes manifestation. A better understanding of the mechanisms governing the changes in the microRNA profile will open the way for the development of new strategies to prevent and/or treat type 2 and gestational diabetes.

The Cells of the Islets of Langerhans

“…The current state of the art is likely to act as a further catalyst for studies in to the α-cell as a result. For example, recent studies focussed on identifying β-cells based on expression profiles of protein-encoding genes and non-coding RNAs, are now also paralleled in α-cells [ 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 ].…”

IRS-2 Partially Compensates for the Insulin Signal Defects in IRS-1−/− Mice Mediated by miR-33

“…They cause translational repression or transcriptional degradation by binding to complementary sites in their 3′ untranslated region (3′ UTR) of target mRNAs (Berindan-Neagoe et al, 2014; Rebustini et al, 2016). miRNAs play key roles in regulating several metabolic processes in pancreatic β-cells, such as insulin biosynthesis, insulin secretion, and β-cell survival (Guay and Regazzi, 2015; Mao et al, 2013). In addition, miRNAs lead dominant roles in cellular differentiation, proliferation, apoptosis, cholesterol biosynthesis, and cancer development (Fernandez-Hernando et al, 2013).…”

MicroRNA in Metabolic Re-Programming and Their Role in Tumorigenesis

“…For instance, miR-375, which is highly expressed in pancreatic islets, is required for normal glucose homeostasis. Knockout of miR-375 induces hyperglycaemia and hyperglucagonaemia, leading to a diabetic state if crossed with obesity and insulin-resistance [ 79 ]. Insulin resistance was found to be positively associated with elevated circulating miR-122 [ 80 ].…”