MicroRNA Sequences Modulated by Beta Cell Lipid Metabolism: Implications for Type 2 Diabetes Mellitus

Abstract

Alterations in lipid metabolism within beta cells and islets contributes to dysfunction and apoptosis of beta cells, leading to loss of insulin secretion and the onset of type 2 diabetes. Over the last decade, there has been an explosion of interest in understanding the landscape of gene expression which influences beta cell function, including the importance of small non-coding microRNA sequences in this context. This review sought to identify the microRNA sequences regulated by metabolic challenges in beta cells and islets, their targets, highlight their function and assess their possible relevance as biomarkers of disease progression in diabetic individuals. Predictive analysis was used to explore networks of genes targeted by these microRNA sequences, which may offer new therapeutic strategies to protect beta cell function and delay the onset of type 2 diabetes.

Diabetes and associated cardiovascular complications: The role of microRNAs

“…The upregulation of miR-34a, which is associated with changes in lipid metabolism in DM, has been strongly linked to β-cell lipotoxicity resulting from exposure to saturated fatty acids. This effect of miR-34a is exerted via the targeting of the gene encoding SIRT1, an nicotinamide adenine dinucleotide (NAD + )-dependent deacetylase, leading to the activation of the expression of NF-κB, STAT3, and the forkhead box class O family member protein (FOXO) family of transcription factors [92] . MiR-34a also targets peroxisome proliferator activator receptor alpha (PPARα) in liver cells, which can affect fatty acid utilization [93] .…”

Modulation of the Cellular microRNA Landscape: Contribution to the Protective Effects of High-Density Lipoproteins (HDL)

“…High-density lipoproteins [ 39 , 40 , 41 , 42 ], apoA-I [ 41 , 43 , 44 , 45 ] and ATP-binding cassette transporters [ 46 , 47 , 48 , 49 , 50 ] also protect beta cells and pancreatic islets in both experimental models and clinical studies [ 51 , 52 , 53 , 54 , 55 ]. While some of these protective functions have been ascribed to sterol removal from beta cells [ 39 , 43 , 44 , 45 , 46 , 47 ], other reports cite the cholesterol- and/or transporter-independent effects of apoA-I and HDL [ 41 , 44 , 56 ].…”

Impaired Physiological Regulation of ß Cells: Recent Findings from Type 2 Diabetic Patients

“…Impaired Physiological Regulation of ß Cells: Recent Findings from Type 2 Diabetic Patients DOI: http://dx.doi.org/10.5772/intechopen.1003752 that microRNA sequences are altered during the β cell lipid metabolism by exposure to high lipids/fats [138][139][140][141][142][143][144][145][146][147][148][149]. Specific proteins responsible for lipid metabolism and cholesterol homeostasis in β cells have been found to be transcriptionally controlled by several microRNAs.…”