Regulation of Pancreatic Beta Cell Stimulus-Secretion Coupling by microRNAs.
Increased blood glucose after a meal is countered by the subsequent increased release of the hypoglycemic hormone insulin from the pancreatic beta cells. The cascade of molecular events encompassing the initial sensing and transport of glucose into the beta cell, culminating with the exocytosis of the insulin large dense core granules (LDCVs) is termed "stimulus-secretion coupling." Impairment in any of the relevant processes leads to insufficient insulin release, which contributes to the development of type 2 diabetes (T2D). The fate of the beta cell, when exposed to environmental triggers of the disease, is determined by the possibility to adapt to the new situation by regulation of gene expression. As established factors of post-transcriptional regulation, microRNAs (miRNAs) are well-recognized mediators of beta cell plasticity and adaptation. Here, we put focus on the importance of comprehending the transcriptional regulation of miRNAs, and how miRNAs are implicated in stimulus-secretion coupling, specifically those influencing the late stages of insulin secretion. We suggest that efficient beta cell adaptation requires an optimal balance between transcriptional regulation of miRNAs themselves, and miRNA-dependent gene regulation. The increased knowledge of the beta cell transcriptional network inclusive of non-coding RNAs such as miRNAs is essential in identifying novel targets for the treatment of T2D.
Unit of Islet Cell Exocytosis, Department of Clinical Sciences in Malmö, Lund University Diabetes Centre, Lund University, CRC 91-11, Jan Waldenströms gata 35, 205 02 Malmö, Sweden. jonathan.esguerra@med.lu.se.
Jonathan L S
JL
Esguerra
Unit of Islet Cell Exocytosis, Department of Clinical Sciences in Malmö, Lund University Diabetes Centre, Lund University, CRC 91-11, Jan Waldenströms gata 35, 205 02 Malmö, Sweden. ines.mollet@med.lu.se.
Inês G
IG
Mollet
Unit of Islet Cell Exocytosis, Department of Clinical Sciences in Malmö, Lund University Diabetes Centre, Lund University, CRC 91-11, Jan Waldenströms gata 35, 205 02 Malmö, Sweden. vishal-salunkhe@med.lu.se.
Vishal A
VA
Salunkhe
Unit of Islet Cell Exocytosis, Department of Clinical Sciences in Malmö, Lund University Diabetes Centre, Lund University, CRC 91-11, Jan Waldenströms gata 35, 205 02 Malmö, Sweden. anna.wendt@med.lu.se.
Anna
A
Wendt
Unit of Islet Cell Exocytosis, Department of Clinical Sciences in Malmö, Lund University Diabetes Centre, Lund University, CRC 91-11, Jan Waldenströms gata 35, 205 02 Malmö, Sweden. lena.eliasson@med.lu.se.
Lena
L
Eliasson