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Pancreatic β cell-derived exosomal miR-29 household enhances hepatic glucose output


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In a brand new examine revealed in Journal of Extracellular Vesicles, Chen-Yu Zhang’s group at Nanjing College, Faculty of Life Sciences, and Antonio Vidal-Puig’s group at College of Cambridge report that pancreatic β cells secrete miR-29 members of the family (miR-29s) by way of exosomes in response to excessive ranges of free fatty acids (FFAs). Theses β cell-derived exosomal miR-29s regulate glucose homeostasis by their manipulations on glucose output in liver.

Beforehand, Chen-Yu Zhang’s group recognized extracellular miRNA as a brand new type of cell-to-cell communication. They’re among the many first that reported the selective secretion of miRNAs beneath completely different physiological or pathological states; additionally, the uptake and performance of secreted miRNAs in recipient cells. Up to now decade, intensive research have revealed the function of extracellular miRNAs in a variety of organic processes. Thus, as a newly-emerged secretory, extra insightful research are have to additional reveal its relevance to extra physiological progresses and ailments. Pancreatic islet has lengthy been recognized as essential secretory tissue in time period of its function on sustaining glucose homeostasis by releasing typical hormones, akin to glucagon and insulin. Since pancreatic islet is a basic secretory organ, examine to determine its secreted miRNAs and their useful implications within the regulation of glucose homeostasis could be very wanted.

Within the present examine, they present that top ranges of FFAs can selectively induce the secretion of miR-29s from cultured pancreatic β cells. In vivo examine revealed each physiological (fasting)-and pathological (overweight)-associated excessive ranges of FFAs induce the secretion of miR-29s from pancreatic β cells. Likewise, miR-29s are additionally elevated within the plasma of overweight human in comparison with regular human. Intriguingly, they found that exosomal miR-29s administrated intravenously could cause impaired insulin sensitivity. Subsequent, they used a mixture of genetic modification animals to additional affirm the useful function of secreted miR-29s. First, mice overexpressed miR-29s in β cells present insulin resistance and an enhanced hepatic glucose output, indicating β cell-derived miR-29s could goal liver and affect hepatic insulin motion. To substantiate this, a distinguishable mutant miR-29a (with 4 nucleotides mutated in non-seed area) was overexpressed in pancreatic β cells of mice. Constantly, these mice present impaired insulin sensitivity. By monitoring the distribution of mutant miR-29a, they discovered β cell-derived mutant miR-29a could be taken up by liver. Mechanism dissections revealed that β cell-derived miR-29s negatively regulate insulin signaling pathway by way of concentrating on p85 α (regulatory subunit of PI3K), and subsequently attenuate the suppression of insulin on glucose output. Lastly, miR-29s deficiency in β cell considerably improves the insulin sensitivity in mice consumed HFD. This examine not solely identifies a brand new secretory issue from pancreatic β cells, but in addition elucidates another mechanism that underlies β cell-controlled glucose homeostasis.

This work is necessary for the next causes:

  1. We show pancreatic islets secrete not solely canonical hormones, but in addition exosomal miRNAs, which is essentially prolonged our understanding of islet perform;
  2. We determine a brand new secretory that play a task in regulation of glucose homeostasis.
  3. We reveal a mechanism underlying weight problems/FFAs-induced insulin resistance and sort 2 diabetes. Weight problems or excessive ranges of FFA could not solely straight have an effect on liver, skeletal muscle and white adipose tissue and trigger insulin resistance, however regulate exogenous secreted miRNA to not directly end in pathophysiology as nicely. Extra importantly, the secreted miR-29s is elevated previous to the onset of insulin resistance in ob/ob mice, indicating secreted miR-29s could be the elements that provoke the event of insulin resistance.
  4. We offer additional proof for the selectivity of secreted miRNAs beneath sure physiological or pathological context.

Researchers uncover course of which will clarify how kind 2 diabetes develops

Extra data:
Jing Li et al, Pancreatic β cells management glucose homeostasis by way of the secretion of exosomal miR‐29 household, Journal of Extracellular Vesicles (2021). DOI: 10.1002/jev2.12055

Supplied by
Nanjing College Faculty of Life Sciences

Pancreatic β cell-derived exosomal miR-29 household enhances hepatic glucose output (2021, January 22)
retrieved 22 January 2021

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