MicroRNAs: a new ray of hope for diabetes mellitus

Abstract

Diabetes mellitus has become one of the most common chronic diseases, thereby posing a major challenge to global health. Characterized by high levels of blood glucose (hyperglycemia), diabetes usually results from a loss of insulin-producing β-cells in the pancreas, leading to a deficiency of insulin (type 1 diabetes), or loss of insulin sensitivity (type 2 diabetes). Both types of diabetes have serious secondary complications, such as microvascular abnormalities, cardiovascular dysfunction, and kidney failure. Various complex factors, such as genetic and environmental factors, are associated with the pathophysiology of diabetes. Over the past two decades, the role of small, single-stranded noncoding microRNAs in various metabolic disorders, especially diabetes mellitus and its complications, has gained widespread attention in the scientific community. Discovered first as an endogenous regulator of development in the nematode Caenorhabditis elegans, these small RNAs post-transcriptionally suppress mRNA target expression. In this review, we discuss the potential roles of different microRNAs in diabetes and diabetes-related complications.

Association study of the miRNA-binding site polymorphisms of CDKN2A/B genes with gestational diabetes mellitus susceptibility

“…Recently, a growing number of studies have revealed that microRNAs (miRNAs) function as genomic regulators, playing critical roles in various physiological processes, including glucose homeostasis and the pathogenesis of type 2 diabetes (T2DM) [5,6]. miRNAs are endogenous, small noncoding RNA molecules approximately 20 nucleotides in length that regulate gene expression posttranscriptionally by pairing to the 3 0 -untranslated region (3 0 UTR) of target gene mRNAs to suppress translation or induce mRNA degradation.…”

MIRNAS: Early Prognostic Biomarkers for Type 2 Diabetes Mellitus?

“…In case of mammals, imperfect base pairing between the miRNA guide strand and the mRNA target may lead to either target mRNA degradation and/or inhibition of protein synthesis [53]. Recent data suggest that miRNAs play a direct role in insulin secretion, pancreatic islet development and pancreatic β-cell differentiation; and indirectly control glucose and lipid metabolism, and are involved in secondary complications associated with diabetes [2]. Interestingly, a conditional knockout of Dicer 1, the sole Dicer enzyme responsible for the biogenesis of miRNAs in humans and mice, led to gross defects in all pancreatic lineages in mice emphasizing the role of miRNAs in diabetes [54].…”

“…Based on the above observations, biofluids like serum and plasma can be stored at -20 or -80°C without substantial degradation of miRNAs. In addition to this, the availability of simple and sensitive approaches for characterization and quantitation of miRNAs (discussed above) make them suitable biomarkers for detection of many diseases [2,14].…”

“…This further leads to elevated levels of glucose in the blood (hyperglycemia), inability of β-cells to compensate for insulin and subsequent β-cell failure/apoptosis leading to T2DM [2]. Even though intensive research is being carried out to understand the pathophysiology of T2DM, the exact miRNAs: early prognostic biomarkers for Type 2 diabetes mellitus?…”

Circulating Nucleic Acids and Diabetes Mellitus

“…It is also involved in the increase in β-cell mass in response to insulin resistance [7,8]. In patients with T1DM and T2DM, the expression profile of miRNA in the β-cell and in insulin sensitive tissues is altered [9][10][11]. In an animal model of T1DM, the NOD mouse, several miRNAs, including miR-21, miR-34a, miR-29 and miR-146a, are increased in the pre-diabetic state [12,13].…”