MicroRNAs contribute to compensatory β cell expansion during pregnancy and obesity

Jacovetti, Cécile; Abderrahmani, Amar; Parnaud, Géraldine; Jonas, Jean‐Christophe; Peyot, Marie‐Line; Cornu, Marion; Laybutt, Ross; Meugnier, Emmanuelle; Rome, Sophie; Thorens, Bernard; Prentki, Marc; Bosco, Domenico; Regazzi, Romano

doi:10.1172/jci64151

Cited by 156 publications

(179 citation statements)

References 77 publications

(95 reference statements)

Supporting

Mentioning

168

Contrasting

Unclassified

Order By: Relevance

“…The expression of several miRNAs is affected by prolonged exposure to elevated concentrations of glucose, NEFA and proinflammatory cytokines [90]. Moreover, alterations in the expression of several islet miRNAs have been reported in different models of diabetes [91,92]. As recently proposed by Nesca et al [93], obesity and insulin resistance trigger changes in the levels of miR-132, miR-184 and miR-338-3p, which promote beta cell mass compensation.…”

Section: Contributors To Maintenance Of Islet Cell Mass In Adult Rodentsmentioning

confidence: 94%

The regulation of pre- and post-maturational plasticity of mammalian islet cell mass

Mezza

Kulkarni

2014

Diabetologia

View full text Add to dashboard Cite

Regeneration of mature cells that produce functional insulin represents a major focus and a challenge of current diabetes research aimed at restoring beta cell mass in patients with most forms of diabetes, as well as in ageing. The capacity to adapt to diverse physiological states during life and the consequent ability to cope with increased metabolic demands in the normal regulation of glucose homeostasis is a distinctive feature of the endocrine pancreas in mammals. Both beta and alpha cells, and presumably other islet cells, are dynamically regulated via nutrient, neural and/or hormonal activation of growth factor signalling and the post-transcriptional modification of a variety of genes or via the microbiome to continually maintain a balance between regeneration (e.g. proliferation, neogenesis) and apoptosis. Here we review key regulators that determine islet cell mass at different ages in mammals. Understanding the chronobiology and the dynamics and agedependent processes that regulate the relationship between the different cell types in the overall maintenance of an optimally functional islet cell mass could provide important insights into planning therapeutic approaches to counter and/or prevent the development of diabetes.

show abstract

Section: Contributors To Maintenance Of Islet Cell Mass In Adult Rodentsmentioning

confidence: 94%

The regulation of pre- and post-maturational plasticity of mammalian islet cell mass

Mezza

Kulkarni

2014

Diabetologia

View full text Add to dashboard Cite

show abstract

“…The expression of several miRNAs is affected by prolonged exposure to elevated concentrations of glucose, NEFA and proinflammatory cytokines [4]. Moreover, alterations in the levels of many islet miRNAs have been reported in different models of diabetes [5][6][7][8][9]. However, the functional impact of these miRNA expression changes and their potential role in the development of diabetes were, in most cases, not explored.…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

Identification of particular groups of microRNAs that positively or negatively impact on beta cell function in obese models of type 2 diabetes

et al. 2013

Self Cite

View full text Add to dashboard Cite

Aims/hypothesis MicroRNAs are key regulators of gene expression involved in health and disease. The goal of our study was to investigate the global changes in beta cell microRNA expression occurring in two models of obesityassociated type 2 diabetes and to assess their potential contribution to the development of the disease. Methods MicroRNA profiling of pancreatic islets isolated from prediabetic and diabetic db/db mice and from mice fed a high-fat diet was performed by microarray. The functional impact of the changes in microRNA expression was assessed by reproducing them in vitro in primary rat and human beta cells. Results MicroRNAs differentially expressed in both models of obesity-associated type 2 diabetes fall into two distinct categories. A group including miR-132, miR-184 and miR-338-3p displays expression changes occurring long before the onset of diabetes. Functional studies indicate that these expression changes have positive effects on beta cell activities and mass. In contrast, modifications in the levels of miR-34a, miR-146a, miR-199a-3p, miR-203, miR-210 and miR-383 primarily occur in diabetic mice and result in increased beta cell apoptosis. These results indicate that obesity and insulin resistance trigger adaptations in the levels of particular microRNAs to allow sustained beta cell function, and that additional microRNA deregulation negatively impacting on insulin-secreting cells may cause beta cell demise and diabetes manifestation. Conclusions/interpretation We propose that maintenance of blood glucose homeostasis or progression toward glucose intolerance and type 2 diabetes may be determined by the balance between expression changes of particular microRNAs.

show abstract

“…A list of the microRNAs identified by these studies is provided in Table 2. Interestingly, a group of microRNAs including miR-34a, miR-132, miR-184, miR-199a-5p, miR-210, miR-212, miR-338-3p and miR-383 was found to be deregulated in different animal models of type 2 diabetes by independent research groups, and changes in their expression were confirmed by real-time PCR quantification [20,21,[29][30][31]. The functional role of some of these microRNAs in the regulation of beta cell function has been investigated in detail.…”

Section: Inappropriate Islet Microrna Expression As a Potential Causementioning

confidence: 98%

“…However, not all the changes in microRNA levels detected in the islets of diabetic animals have deleterious effects on beta cell activities. Indeed, reduction of miR-184 and miR-338-3p or a rise of miR-132 was found to trigger beta cell proliferation and improve survival and/or insulin release [20,21,31,33]. This suggests that these changes contribute to physiological processes that attempt to compensate for insulin resistance rather than to pathological events causing the appearance of diabetes.…”

Section: Inappropriate Islet Microrna Expression As a Potential Causementioning

confidence: 99%

“…This is an important issue because it is often difficult to determine whether microRNAs differentially expressed in the islets of overtly diabetic individuals are a direct cause of the disease or are the consequence of the chronic exposure of islet cells to the elevated levels of glucose, lipids and inflammatory mediators that typically occur under diabetes conditions. As mentioned above, certain modifications in islet microRNA expression may even have a positive impact on islet function [20,21,31] and be part of the physiological mechanisms involved in meeting the rise in insulin requirements caused by insulin resistance in peripheral tissues of obese and ageing individuals.…”

Section: Can Findings Obtained From Animal Models Of Diabetes Be Extrmentioning

confidence: 99%

See 1 more Smart Citation

Role of islet microRNAs in diabetes: which model for which question?

Guay

Regazzi

2014

Diabetologia

Self Cite

View full text Add to dashboard Cite

MicroRNAs are important regulators of gene expression. The vast majority of the cells in our body rely on hundreds of these tiny non-coding RNA molecules to precisely adjust their protein repertoire and faithfully accomplish their tasks. Indeed, alterations in the microRNA profile can lead to cellular dysfunction that favours the appearance of several diseases. A specific set of microRNAs plays a crucial role in pancreatic beta cell differentiation and is essential for the fine-tuning of insulin secretion and for compensatory beta cell mass expansion in response to insulin resistance. Recently, several independent studies reported alterations in microRNA levels in the islets of animal models of diabetes and in islets isolated from diabetic patients. Surprisingly, many of the changes in microRNA expression observed in animal models of diabetes were not detected in the islets of diabetic patients and vice versa. These findings are unlikely to merely reflect species differences because microRNAs are highly conserved in mammals. These puzzling results are most probably explained by fundamental differences in the experimental approaches which selectively highlight the microRNAs directly contributing to diabetes development, the microRNAs predisposing individuals to the disease or the microRNAs displaying expression changes subsequent to the development of diabetes. In this review we will highlight the suitability of the different models for addressing each of these questions and propose future strategies that should allow us to obtain a better understanding of the contribution of microRNAs to the development of diabetes mellitus in humans.Keywords Animal models of Diabetes . Diabetes . Human islet donors . Insulin . Islets of Langerhans . MicroRNAs . Pancreatic beta cells . Review MicroRNAs as regulators of beta cell differentiation and functionType 2 diabetes is a chronic metabolic disorder characterised by major alterations in gene expression, which affects several organs, including the islets of Langerhans. A growing number of studies demonstrate that these changes are not only caused by deregulation of key transcription factors such as v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A (avian) (MafA) or pancreatic and duodenal homeobox 1 (PDX1) but are also driven by modifications in the level of another group of molecules regulating gene expression, the microRNAs [1][2][3][4]. MicroRNAs are small non-coding RNAs (typically 21-23 nucleotides long) that pair to the 3′ untranslated region of target mRNAs leading to translational repression and/or a decrease in messenger stability [5].The importance of the microRNA regulatory network for proper differentiation and function of beta cells is highlighted by the phenotypic traits of mice lacking Dicer1, an enzyme essential for the generation of most microRNAs [5]. Deletion of Dicer1 at different stages of pancreas development or of the pancreatic endocrine lineage results in a dramatic loss of microRNAs, accompanied by severe defects in pancreas m...

show abstract

MicroRNAs contribute to compensatory β cell expansion during pregnancy and obesity

Cited by 156 publications

References 77 publications

The regulation of pre- and post-maturational plasticity of mammalian islet cell mass

The regulation of pre- and post-maturational plasticity of mammalian islet cell mass

Identification of particular groups of microRNAs that positively or negatively impact on beta cell function in obese models of type 2 diabetes

Role of islet microRNAs in diabetes: which model for which question?

Contact Info

Product

Resources

About