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The global pandemic is real, with almost 8,000 deaths worldwide and nearly 200,000 persons having contracted the virus in 155 affected countries. What is particularly comforting for this country, amid pain and the not knowing, is the bedside and...

When I tell people that I do not remember learning how to read, they laugh. But I really do not recall learning to read. Reading was an activity that excited my family, and so it was no surprise that I would love reading. The love of books and...

Between December 2019 and February 2020, The Gleaner published a series of articles on my behalf, exploring the issue of food security in Jamaica based on an analysis of the country’s food-import bill for 2018. The current COVID-19 pandemic, which...

Government, having said bye, bye to the International Monetary Fund (IMF), declared quite boldly that it was ready to take charge and defend, on its own, the country’s economic independence. For the Government to swallow its pride and say, “Please...

A few days ago as the lady and I drove out, headed to the hardware store to purchase one piece of lumber, she was wearing a face mask, and I had mine on the seat behind me. “So, what’s the point of you wearing the mask in the car and me without...

Public reaction to the initial threat of the coronavirus (COVID-19) was predictably mixed. While international news of the contagion across continents helped people to appreciate that this was not restricted to a particular region, not many people...

On Tuesday, April 14, the International Monetary Fund downgraded Jamaica’s growth prospects to -5.6 per cent. This is a severe contraction warranting substantial Government intervention. However, at times, the Government waits too late to respond...

Four companies involved in one of America’s “largest price-fixing cases” are now behind the anti-malaria drug touted by Donald ‘The Great Impeached’ Trump as a snake-oil, cure-all treatment for COVID-19, caused by the novel coronavirus. Several...

The global COVID-19 spread has gone from bad to worse, with over 3.2 million confirmed cases and close to 250,000 deaths, not only has this pandemic claimed innumerable lives, it has also destabilised economies by freezing trade and other economic...

The national priority at this time must be the protection of the Jamaican people against the onset of COVID-19. This has to be done by striking the balance between implementing protective public-health measures and providing a supporting economic...

Michelle Thomas has joined the ranks of society’s young movers and shakers in her capacity as a lawyer. The work truly began after she was crowned Miss Kingston and St Andrew Festival Queen in 2015. Since then, she has been pushing for more female...

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Monique Lynch is a 29-year-old who believes her purpose is to improve the lives of those around her, especially the downtrodden and persons living with mental health issues. This angel-on-earth in the eyes of many is a Jill of several trades as...

Everyone these days is so focused on the beauty behind hair and skincare lines that they neglect to really explore the science behind them. Creating revolutionary products that are not only innovative but eco-friendly is entrepreneur Antoinette...

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We’ve heard this rhetoric in RnB jams: love is blind. So it’s nothing new. But Netflix decided to test its theory with a show, designed to prove whether or not love can be truly blind, in its literal sense. It’s not until watching the episodes that...

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At age 13, Nadeen Matthews Blair, chief executive officer of the NCB Foundation, challenged the tide to prove to a guidance counsellor at her United States-based school, that black girls can overcome all odds to become powerful leaders. Matthews...

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Famous American poet and singer Maya Angelou shared this about matters pertaining to the heart: “Love recognises no barriers. It jumps hurdles, leaps fences, penetrates walls to arrive at its destination full of hope.” What started out as an...

Women with endometriosis have significantly higher rates of depression than women in the general population. That’s according to psychiatrist Dr Kristen Robinson-Barrett. It’s the end of endometriosis month, so Flair spoke to the expert to explore...

It is definitely a make-or-break season for those trying to balance career and COVID-19 at home. For some, it is the ideal time to reconnect with themselves, family members and get creative with work. While with others, the cookie crumbles and they...

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A sufficient β-cell mass is crucial for preventing diabetes, and perinatal β-cell proliferation is important in determining the adult β-cell mass. However, it is not yet known how perinatal β-cell proliferation is regulated. Here, we report that serotonin regulates β-cell proliferation through serotonin receptor 2B (HTR2B) in an autocrine/paracrine manner during the perinatal period. In β-cell–specific Tph1 knockout (Tph1 βKO) mice, perinatal β-cell proliferation was reduced along with the loss of serotonin production in β-cells. Adult Tph1 βKO mice exhibited glucose intolerance with decreased β-cell mass. Disruption of Htr2b in β-cells also resulted in decreased perinatal β-cell proliferation and glucose intolerance in adulthood. Growth hormone (GH) was found to induce serotonin production in β-cells through activation of STAT5 during the perinatal period. Thus, our results indicate that GH-GH receptor-STAT5-serotonin-HTR2B signaling plays a critical role in determining the β-cell mass by regulating perinatal β-cell proliferation, and defects in this pathway affect metabolic phenotypes in adults.

Active maintenance of β-cell identity through fine-tuned regulation of key transcription factors ensures β-cell function. Tacrolimus, a widely used immunosuppressant, accelerates onset of diabetes after organ transplantation, but underlying molecular mechanisms are unclear. Here we show that tacrolimus induces loss of human β-cell maturity and β-cell failure through activation of the BMP/SMAD signaling pathway when administered under mild metabolic stress conditions. Tacrolimus-induced phosphorylated SMAD1/5 acts in synergy with metabolic stress–activated FOXO1 through formation of a complex. This interaction is associated with reduced expression of the key β-cell transcription factor MAFA and abolished insulin secretion, both in vitro in primary human islets and in vivo in human islets transplanted into high-fat diet–fed mice. Pharmacological inhibition of BMP signaling protects human β-cells from tacrolimus-induced β-cell dysfunction in vitro. Furthermore, we confirm that BMP/SMAD signaling is activated in protocol pancreas allograft biopsies from recipients on tacrolimus. To conclude, we propose a novel mechanism underlying the diabetogenicity of tacrolimus in primary human β-cells. This insight could lead to new treatment strategies for new-onset diabetes and may have implications for other forms of diabetes.

The molecular mechanisms of β-cell compensation to metabolic stress are poorly understood. We previously observed that nutrient-induced β-cell proliferation in rats is dependent on epidermal growth factor receptor (EGFR) signaling. The aim of this study was to determine the role of the EGFR ligand heparin-binding EGF-like growth factor (HB-EGF) in the β-cell proliferative response to glucose, a β-cell mitogen and key regulator of β-cell mass in response to increased insulin demand. We show that exposure of isolated rat and human islets to HB-EGF stimulates β-cell proliferation. In rat islets, inhibition of EGFR or HB-EGF blocks the proliferative response not only to HB-EGF but also to glucose. Furthermore, knockdown of HB-EGF in rat islets blocks β-cell proliferation in response to glucose ex vivo and in vivo in transplanted glucose-infused rats. Mechanistically, we demonstrate that HB-EGF mRNA levels are increased in β-cells in response to glucose in a carbohydrate-response element–binding protein (ChREBP)–dependent manner. In addition, chromatin immunoprecipitation studies identified ChREBP binding sites in proximity to the HB-EGF gene. Finally, inhibition of Src family kinases, known to be involved in HB-EGF processing, abrogated glucose-induced β-cell proliferation. Our findings identify a novel glucose/HB-EGF/EGFR axis implicated in β-cell compensation to increased metabolic demand.

Loss of functional β-cell mass is an essential feature of type 2 diabetes, and maintaining mature β-cell identity is important for preserving a functional β-cell mass. However, it is unclear how β-cells achieve and maintain their mature identity. Here we demonstrate a novel function of protein arginine methyltransferase 1 (PRMT1) in maintaining mature β-cell identity. Prmt1 knockout in fetal and adult β-cells induced diabetes, which was aggravated by high-fat diet–induced metabolic stress. Deletion of Prmt1 in adult β-cells resulted in the immediate loss of histone H4 arginine 3 asymmetric dimethylation (H4R3me2a) and the subsequent loss of β-cell identity. The expression levels of genes involved in mature β-cell function and identity were robustly downregulated as soon as Prmt1 deletion was induced in adult β-cells. Chromatin immunoprecipitation sequencing and assay for transposase-accessible chromatin sequencing analyses revealed that PRMT1-dependent H4R3me2a increases chromatin accessibility at the binding sites for CCCTC-binding factor (CTCF) and β-cell transcription factors. In addition, PRMT1-dependent open chromatin regions may show an association with the risk of diabetes in humans. Together, our results indicate that PRMT1 plays an essential role in maintaining β-cell identity by regulating chromatin accessibility.

Human but not mouse islets transplanted into immunodeficient NSG mice effectively accumulate lipid droplets (LDs). Because chronic lipid exposure is associated with islet β-cell dysfunction, we investigated LD accumulation in the intact human and mouse pancreas over a range of ages and states of diabetes. Very few LDs were found in normal human juvenile pancreatic acinar and islet cells, with numbers subsequently increasing throughout adulthood. While accumulation appeared evenly distributed in postjuvenile acinar and islet cells in donors without diabetes, LDs were enriched in islet α- and β-cells from donors with type 2 diabetes (T2D). LDs were also found in the islet β-like cells produced from human embryonic cell–derived β-cell clusters. In contrast, LD accumulation was nearly undetectable in the adult rodent pancreas, even in hyperglycemic and hyperlipidemic models or 1.5-year-old mice. Taken together, there appear to be significant differences in pancreas islet cell lipid handling between species, and the human juvenile and adult cell populations. Moreover, our results suggest that LD enrichment could be impactful to T2D islet cell function.

Aging-dependent changes in tissue function are associated with the development of metabolic diseases. However, the molecular connections linking aging, obesity, and diabetes remain unclear. Lamin A, lamin C, and progerin, products of the Lmna gene, have antagonistic functions on energy metabolism and life span. Lamin C, albeit promoting obesity, increases life span, suggesting that this isoform is crucial for maintaining healthy conditions under metabolic stresses. Because β-cell loss during obesity or aging leads to diabetes, we investigated the contribution of lamin C to β-cell function in physiopathological conditions. We demonstrate that aged lamin C only–expressing mice (Lmna^LCS/LCS) become obese but remain glucose tolerant due to adaptive mechanisms including increased β-cell mass and insulin secretion. Triggering diabetes in young mice revealed that Lmna^LCS/LCS animals normalize their fasting glycemia by both increasing insulin secretion and regenerating β-cells. Genome-wide analyses combined to functional analyses revealed an increase of mitochondrial biogenesis and global translational rate in Lmna^LCS/LCS islets, two major processes involved in insulin secretion. Altogether, our results demonstrate for the first time that the sole expression of lamin C protects from glucose intolerance through a β-cell–adaptive transcriptional program during metabolic stresses, highlighting Lmna gene processing as a new therapeutic target for diabetes treatment.

The host environment is a crucial factor for considering the transplant of stem cell–derived immature pancreatic cells in patients with type 1 diabetes. Here, we investigated the effect of insulin (INS)-deficient diabetes on the fate of immature pancreatic endocrine cell grafts and the underlying mechanisms. Human induced pluripotent stem cell–derived pancreatic endocrine progenitor cells (EPCs), which contained a high proportion of chromogranin A⁺ NK6 homeobox 1⁺ cells and very few INS⁺ cells, were used. When the EPCs were implanted under the kidney capsule in immunodeficient mice, INS-deficient diabetes accelerated increase in plasma human C-peptide, a marker of graft-derived INS secretion. The acceleration was suppressed by INS infusion but not affected by partial attenuation of hyperglycemia by dapagliflozin, an INS-independent glucose-lowering agent. Immunohistochemical analyses indicated that the grafts from diabetic mice contained more endocrine cells including proliferative INS-producing cells compared with that from nondiabetic mice, despite no difference in whole graft mass between the two groups. These data suggest that INS-deficient diabetes upregulates the INS-secreting capacity of EPC grafts by increasing the number of endocrine cells including INS-producing cells without changing the graft mass. These findings provide useful insights into postoperative diabetic care for cell therapy using stem cell–derived pancreatic cells.

Approximately 10% of patients with type 2 diabetes suffer from latent autoimmune diabetes in adults (LADA). This study provides a systematic assessment of the pathology of the endocrine pancreas of patients with LADA and for comparison in a first rat model mimicking the characteristics of patients with LADA. Islets in human and rat pancreases were analyzed by immunohistochemistry for immune cell infiltrate composition, by in situ RT-PCR and quantitative real-time PCR of laser microdissected islets for gene expression of proinflammatory cytokines, the proliferation marker proliferating cell nuclear antigen (PCNA), the anti-inflammatory cytokine interleukin (IL) 10, and the apoptosis markers caspase 3 and TUNEL as well as insulin. Human and rat LADA pancreases showed differences in areas of the pancreas with respect to immune cell infiltration and a changed ratio between the number of macrophages and CD8 T cells toward macrophages in the islet infiltrate. Gene expression analyses revealed a changed ratio due to an increase of IL-1β and a decrease of tumor necrosis factor-α. IL-10, PCNA, and insulin expression were increased in the LADA situation, whereas caspase 3 gene expression was reduced. The analyses into the underlying pathology in human as well as rat LADA pancreases provided identical results, allowing the conclusion that LADA is a milder form of autoimmune diabetes in patients of an advanced age.

Here are answers to some of the primary questions you may have as the defending National League East champs prepare to begin Spring Training next week.

The Braves made it clear that, individually, each of their prospects was available in exchange for J.T. Realmuto. But they were not willing to provide the volume of prospects or the MLB-experienced asset sought by the Marlins, who ended an offseason-long saga by dealing the All-Star catcher to the Phillies on Thursday.

Reporter Mark Bowman addresses the Braves' offseason as a whole, as well as identifying a Minor League who has a chance at making the club out of Spring Training.

At some point over the next six weeks, injuries, improvement or regression will inevitably alter the plan nearly every Major League club brings into Spring Training. The Braves must decide exactly how to round out their rotation and bullpen, but for now it looks like they won't have any position-player battles. Here's the first prediction of how Atlanta's Opening Day roster might look.

We're reluctant to finalize our list of offseason winners because, as you may have heard, there are some prominent unsigned free agents. Not just Bryce Harper and Manny Machado, either.

Here is a look at 10 Braves players sure to draw attention during this year's Spring Training.

When the Braves re-signed Nick Markakis in January, they began leaning toward putting Ender Inciarte in the leadoff spot and moving Ronald Acuna Jr. to the cleanup role. But manager Brian Snitker said Acuna may still get his wish to stay at the top of the lineup.

As Braves manager Brian Snitker evaluates who might serve as his closer, A.J. Minter has made it clear he wants to be the guy who is consistently called upon to handle high-leverage threats that develop in late innings.

The next five weeks will see lots of shuffling on Major League rosters. Here are the most intriguing positional battles on each of the 30 MLB clubs.

It could be argued that Ender Inciarte stands as the X-factor in regard to the Braves' bid to defend last year's National League East crown and experience a successful postseason.

Having seen what Luiz Gohara had done upon his introduction to the big leagues the previous September, Freddie Freeman told Alex Anthopoulos the big left-hander might immediately became an All-Star. Instead, it became a year of awakening for the young hurler, who remains fueled by last year's disappointments.

Braves manager Brian Snitker joked that he could almost detect a smile as he shared a phone conversation with Nick Markakis after the stoic outfielder re-signed with the club in January. Snitker and others actually saw that smile on Tuesday morning, when Markakis reported to Spring Training to begin his fifth season with the Braves and attempt to push the club past the rebuild he positively enriched through his leadership.

To those of a certain age, Frank Robinson was the definition of greatness, leadership and toughness. Well into his 70's and 80's, he carried himself with the confidence and unmistakable gait of a great athlete.

In outlining their plans to rebuild the Orioles following the least successful season in franchise history, new club officials routinely point to experience: They just did the same thing elsewhere.

Frank Robinson, a trailblazing figure who was Major League Baseball's first African-American manager and one of its greatest players during a career that spanned 21 seasons, died Thursday after a prolonged illness. He was 83.

The Orioles' restocked farm system might inject some excitement into the club's retooled roster.