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However, little is known about its molecular mechanisms. Given the emerging importance of microRNAs in various metabolic diseases, in this study a possible link between the effects of T2 on glucose metabolism and miRNA expression was investigated by using an in vivo model in which T2 was administered in rats receiving a high fat diet, a condition known to impair glucose homeostasis.
The results showed that T2-treated rats had a better tolerance to glucose load and a better performance at the insulin tolerance test in comparison to high fat diet animals. Interestingly, in the serum of the animals treated with T2 there was a general decrease of miRNAs with miRa-3p, miRc-5p and miRa-3p significantly downregulated. Furthermore, miRa-3p had the largest variation pointing toward its preeminent role in T2 metabolic effect.
In fact, in liver there was an up-regulation of its target Transcription Factor 7 Tcf7, which had an important impact on gluconeogenesis. This study provide, for the first time, evidences that miRNAs are involved in the effects exerted by T2 on glucose homeostasis.
In the last years, several data have shown that some THs derivatives natural metabolites and analogues play a relevant biological role on the metabolism for reviews see 345678. Among these, many studies are focused on 3,5-diiodo-L-thyronine T2a biologically active iodothyronine 91011 for review see 7121314 Interestingly, it has been also shown that T2 administration to HFD-fed rats improved glucose tolerance, insulin sensitivity 18 and gluconeogenesis in hepatocytes Furthermore, a possible physiological link between glucose metabolism 1920 and circulating T2 has been highlighted by findings from a healthy euthyroid population.
To date, however, the mechanism by which T2 affects glucose homeostasis remains to be clarified. Many reports have demonstrated the involvement of miRNAs in various diseases 212223mainly in the etiology of cancer but also in metabolic disorders such as obesity and type 2 diabetes T2D 2425 which, in turn, are characterized by an impaired glucose homeostasis 26 Indeed, these small non-coding RNA molecules modulate the levels of kinases and enzymes in the glucose metabolism 28 by affecting posttranscriptional regulation of gene expression.
Based on those considerations, the aim of this study was to examine the potential involvement of miRNAs in the mechanisms of action by which T2 affects glucose homeostasis in rats fed on a high-fat-diet. This animal model was chosen since HFD treated rats showed an altered glucose homeostasis and some metabolic disorders, such as altered glucose tolerance and insulin-resistance, thus revealing the beneficial effect of a T2 treatment.
In particular: a a screening of circulating miRNA changes in the serum from HFD-T2 treated vs HFD rats was performed to identify miRNAs potentially involved in the effects of T2; b the top-ranked microRNA from the screening, rno-miRp miRwas further investigated in relation to its possible transcript targets involved in glucose metabolism. After four weeks of treatment, HFD-T2 rats had accumulated less fat.
These results are consistent with the action of T2 in counteracting gain in body weight and fat accumulation during an HFD diet 33 In fact, the oral glucose tolerance test revealed that, after a glucose load, the animals treated with T2 had a better tolerance to this sugar compared to HFD rats Fig.
Furthermore, the insulin tolerance test showed that the reduction in the glycaemia after insulin administration was almost the same in HFD-T2 and N animals, but was impaired in HFD animals Fig. These data indicate that T2 could prevent the development of insulin resistance induced by a hyperlipidic diet. Overall, the data indicate that T2 administration prevents body weight gain and increased adiposity without inducing a thyrotoxic state, and improve glucose tolerance and insulin sensitivity.
Circulating miRp. Moreover, miR has been reported to have as direct target the Wnt-responsive transcription Factor Tcf7 in mouse and human cells, thus impairing gluconeogenesis and, as consequence, an increase in circulatory glucose level These data prompted us to investigate this pathway in our experimental rat model. First, miR expression was measured in the liver, revealing that T 2 administration to HFD-fed rats significantly reduced miR expression when compared to HFD-fed rats; in HFD rats, the miRa expression was increased, although not significantly when compared to N animals Fig.
Hepatic expression of miR and of its Tcf7 target. Finally, in the same samples, we also analyzed the expression levels of genes of gluconeogenesis, i. Consistently, in our in vivo model a strong decrease in the expression of G6Pase and FBPase was observed in response to T2 administration Fig.
Furthermore, T2 treatment prevented the increase in glycolytic enzyme liver pyruvate kinase LPK induced by hyperlipidic diet Fig.
Hepatic expression of rate-limiting genes of gluconeogenesis. It is well established that T2 exerts considerable effects on the metabolic activities.
'No Time To Say Goodbye' How The Coronavirus Is Changing Learning
Indeed, several laboratories have demonstrated that it is able to influence both the energy metabolism and some biochemical pathways involved in lipid and glucose metabolism 91013Ordinarily, Russo would greet each of the 28 seven and eight year olds in her care with a handshake, hello or high-five as they filed through the door of her classroom each morning.
Today, that doorway is a different type. The coronavirus pandemic means teachers like Russo are rewriting the book on how to be a classroom teacher. As schools close and distance learning programs continue into their second month, families with access to technology are seeing laptops and keyboards replacing doors, desks and chalkboards. When the coronavirus pandemic forced all Wisconsin schools to close on March 13, officials initially thought they could reopen by April 6.
We just had no warning, and it was a very emotional thing," she said. As the number of confirmed COVID cases and deaths in Wisconsin continued to rise, state officials shut school systems down for the remainder of the spring semester. Russo said this year's class is one of the best she's had in her 30 years of teaching. A big part of that has to do with the school's push to focus on social-emotional health. The class has worked together to practice mindfulness, learn how to articulate and express feelings, and focus on problem-solving to overcome the bumps and hiccups that accompany a second-grader's journey through life.
It's so important to me, and always has been," she said. When one parent told Russo she couldn't get her child to read, Russo created a Bingo calendar that motivated the otherwise stubborn student to pick up books on their own. Russo said she has several students who take daily journaling to heart.
Some students type out a sentence or two, but some have deepened their relationship with Russo. One of Russo's favorite projects is her "flat teacher" project.
Russo printed out 28 pictures of herself, cut them out, laminated them and put them in packets that were mailed to each of the students. Her students have instructions to have their photo taken with their "flat teacher" at varying points of the day. Her days are no longer governed by bells and bus schedules, and are more in tune with the rhythms of everyday life during the coronavirus pandemic. When Russo and six fellow Gifford teachers began meeting online to figure out new modes of teaching, it started with the realization that Gifford's seven-hour school day has been pared down to about two hours of home instruction.
The team works together to pull together resources and work materials to send home or post online. They're still working and I have a lot of them in the medical field," she said. It there if they want it, and it's there if they need it.
Some parents want more material. While there are the staples: reading, math and social studies, there are other second-grade strategies that Russo has found enjoyment in providing. She set up a private Facebook group for her class where she does a read-aloud.Enter your mobile number or email address below and we'll send you a link to download the free Kindle App.
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Hilarious and true-to-life, witty, compassionate, and impossible to put down, Straight Man follows Hank Devereaux through one very bad week in this novel from Pulitzer Prize-winning author Richard Russo.
William Henry Devereaux, Jr. Devereaux's reluctance is partly rooted in his character--he is a born anarchist--and partly in the fact that his department is more savagely divided than the Balkans. In the course of a single week, Devereaux will have his nose mangled by an angry colleague, imagine his wife is having an affair with his dean, wonder if a curvaceous adjunct is trying to seduce him with peach pits, and threaten to execute a goose on local television.
All this while coming to terms with his philandering father, the dereliction of his youthful promise, and the ominous failure of certain vital body functions. In short, Straight Man is classic Russo—side-splitting, poignant, compassionate, and unforgettable. Read more Read less. Kindle Cloud Reader Read instantly in your browser. Frequently bought together.
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Add all three to Cart Add all three to List. Ships from and sold by Amazon. Customers who viewed this item also viewed. Page 1 of 1 Start over Page 1 of 1. Empire Falls. Richard Russo. The Risk Pool. Lightning Rods. Register a free business account. Review "The funniest serious novel I have read since--well, maybe since Portnoy's Complaint.Modern Torrent Stream technology, which is implemented in the program, allows you to view high-quality video without delay.
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