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Bile acids are the end products of cholesterol catabolism and play an important role in maintaining cholesterol homeostasis and preventing the buildup of toxic metabolites, as well as the accumulation of cholesterol . Studies have (pop over to this website) demonstrated that bile acids are closely associated with the intestinal microbiota, which intimately affects gut hormones . Regulation of feeding, metabolism, disease development, and homeostasis may be the result of their interactions and mutual influence . On the one hand, bile acids not only facilitate transport of lipids and intestinal absorption but are also inflammatory agents and signaling molecules that effectively activate cell signaling pathways that regulate glucose, lipids, and energy metabolism . On the other hand, accumulating studies have suggested that bile acids could activate certain receptors, such as the farnesoid X receptor (FXR) and the transmembrane G protein-coupled receptor 5 (TGR5), which improves glucose tolerance, insulin sensitivity, and energy metabolism . The effects of these receptors suggest that bile acids may represent a potential therapeutic target for treating T2DM. This review is aimed at summarizing the effects of and changes in bile acids and their main receptors, such as FXR and TGR5, in T2DM development and their promise of representing potential treatment targets for T2DM.

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The progression, initially signalling that she wanted to do away with private insurers completely, likely alienated centrists, Kamarck said. But when Warren later presented a more moderate plan, it came across as a cop-out to many progressives in the party.

In this review, we focused on the role of bile acids in glucose metabolism and the occurrence and development of T2DM, as well as the possibility of bile acids representing a new target for treating T2DM. Without a doubt, bile acids are exceedingly significant in glucose metabolism. Their important roles in the occurrence and development of T2DM have drawn plentiful attention. A mass of research findings have shown that there might be transformations of bile acids in their metabolism concomitant with the occurrence of T2DM, to some extent, leading to abnormal glucose metabolism and insulin resistance. However, additional studies are needed to verify these alterations and to understand the specific interactions that are occurring. Additionally, further animal experiments and clinical trials are required to support the safety and efficacy of bile acids and their sequestrants. Importantly, novel methods of targeted therapy for T2DM have (https://srirejekifastboat.com/serial-code/?file=646) recently been identified, and the future of T2DM treatment is becoming more promising.


Currently, studies of FXR-targeting therapies for T2DM are extremely limited. Obeticholic acid (OCA), a semisynthetic bile acid, is 30 times more effective in activating FXR than CDCA. Although it was not used for diabetes treatment, its effects in inhibiting bile acid synthesis and improving liver function have been verified in the treatment of metabolic liver diseases [100, 101]. Since FXR activation inhibits hepatic glucose synthesis to decrease fasting plasma glucose, it is likely that similar to OCA, targeting FXR represents a novel strategy for improving hyperglycemia in T2DM.

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Her father worked as a janitor, salesman, and mechanic. Before getting into politics, she taught children with special needs at a public elementary school in Texas. She eventually got her law degree and taught at a number of law schools across the US.

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Glucose regulation improves when TGR5 signaling increases [81, 82]. Glucagon-like peptide 1 (GLP-1) promotes insulin secretion by islet beta cells in a glucose-dependent manner and reduces glucagon secretion by islet alpha cells, thereby lowering blood glucose. Secretion of GLP-1 is enhanced in response to TGR5 signaling activation in gastrointestinal enteroendocrine L cells . In addition to its glucose-dependent insulinotropic effect, GLP-1 has similar properties to glucagon and induces satiety. Bile acids may regulate glucose homoeostasis, appetite, and even body weight via TGR5 [84–86]. Some studies have reported that TGR5 is a downstream target of FXR and it is required for promoting GLP-1 secretion through L cell FXR signaling . The specific role of TGR5 in the regulation of glucose homeostasis requires further study, but activation of TGR5 does convey an apparent beneficial effect on glucose homeostasis.

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Numerous studies have shown that FXR is closely related to glucose metabolism. Diabetic rats induced by streptozotocin exhibited reduced FXR expression in the liver, which can be restored by insulin supplementation . FXR knockout mice exhibited a distinct response to refeeding in hepatic expression of glucose metabolism genes . Elevated glucose influx and activation of insulin signaling may lead to postprandial bile acid synthesis . A previous study demonstrated that high concentrations of bile acids stimulate ligand-dependent FXR transactivating activity and increase cellular glucose flux . During the postprandial phase, FXR may be activated to regulate glucose homeostasis [75, 77, 78]. Recent studies suggested that FXR regulates the sensitivity and secretion of peripheral insulin and promotes glycogen synthesis by inducing FGF15 (FGF19 in humans) in the intestine . In addition, FGF19 directly activates SHP by combining with FGFR4 with the help of klotho β in hepatocytes (Figure 3).


According to Fisco, Blethen has dedicated resources to the initiative by “(mobilizing) a team at the Times to expand coverage of free press related issues. This includes the hiring of a Free Press writer position within the editorial staff, specifically focused on exposing threats and solutions to the national free press system.

Metabolism of Bile Acids

The tax would apply to households with a net worth of $50m or more, applying to roughly 75,000 of the wealthiest households in the country, according to University of California Berkeley economists Emmanuel Saez and Gabriel Zucman, whose research Warren’s plan cites. These households would pay a 2 percent tax on every dollar of net worth above that amount and a 6 percent tax on every dollar above a net worth of one billion dollars.

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T2DM is generally considered a progressive, incurable, and increasingly prevalent illness characterized by insulin resistance and a deficiency in the absence of autoimmune beta-cell destruction, accounting for 90-95% of all diabetes cases . Furthermore, it has become the most challenging endocrine disease and a leading cause of mortality worldwide, which by all predictions will only increase . With rapid urbanization, economic growth, and changes in lifestyles, the prevalence of T2DM in China is increasing significantly, representing a serious problem that causes a significant burden on society . The pathogenesis of T2DM is not yet entirely clear, and some evidence suggests it may be related to obesity, ethnicity, and environmental risk factors . Recently, emerging evidence has suggested that insulin resistance may be the most important contributor . Obese individuals tend to develop inflammation in their fat tissue, reducing the sensitivity of fat cells to insulin and inducing the development of T2DM and diminished effects of insulin . Furthermore, T2DM frequently causes microvascular pathological changes, leading to stroke, heart failure, renal failure, and myocardial infarction in late stages, leading to poor prognosis and quality of life in patients . Currently, treatment of T2DM comprises five primary methods: education for patients, self-monitoring of blood glucose, diet, exercise, and medication . However, these methods are expensive and inefficient. Hence, diagnosis is often delayed until complications have arisen and financial costs for the treatment of T2DM have become significant, indicating the urgent need to develop new and efficient therapies and prevention methods for the control of type 2 diabetes.


Despite all the curveballs that have been thrown at them this year, the Times also received some good news in May when the paper received a Pulitzer Prize in National Reporting for stories that exposed design flaws in the Boeing 737 MAX that led to two deadly crashes and revealed failures in government oversight. Out of the 11 Pulitzer Prizes the Times has won, Blethen has been publisher for eight of those awards. In addition, the Times has been a finalist 14 times—all under Blethen’s watch.

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In September, the Working Families Party, a national organisation with an extensive grassroots network of unions and community organisations, endorsed Warren. The group, which had resoundingly backed Sanders in 2021, faced backlash for the pivot.

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This issue was originally opened by @gcontrer87 as hashicorp/terraform#24323. It was migrated here as a result of the provider split. The original body of the issue is below.


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Trump has already seized on – largely disproven – accusations that Warren had benefitted professionally from embellishing her Native American ancestry, in particular, during her time at the University of Pennsylvania and Harvard. The president often refers to the senator derisively as “Pocahontas”, while portraying the allegations as evidence of her dishonesty.

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Bile Acids in the Regulation of Glucose Homeostasis

Like Sanders, Warren has eschewed soliciting money from wealthy donors and has pledged to continue that policy into the general election, with some caveats. Warren took in nearly $25m in one three-month period, she announced in October, just slightly less than Sanders during that time. With the average donation at just $26, the gains served as proof positive of Warren’s formidable base.


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House of Representatives in July. The Act would provide tax credits to local newspapers. At press time, there were 66 cosponsors to the bill.


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She now faces a narrowing field in what began as one of the US’s most crowded and diverse races for the Democratic nomination. National polls have (their website) Warren regularly placing among the top three candidates, along with fellow progressive Senator Bernie Sanders and centrist frontrunner former Vice President Joe Biden. Her showing, along with that of Sanders, implies that candidates once considered too far left are resonating with a growing number of liberals.

Recently, accumulating studies have shown that bile acids are involved in systemic metabolism, pancreatic islet insulin resistance, hyperglycemia regulation, and energy expenditure [28, 29]. Abnormal BA metabolism is closely related to a variety of metabolic diseases, such as obesity, dyslipidemia, and nonalcoholic fatty liver disease. In addition, bile acids have (see post) been proven to be involved in glucose and lipid metabolism . Therefore, we will focus on changes in BA metabolism in T2DM.


Seattle Mayor Jenny Durkan meets with Seattle Times publisher Frank Blethen and the editorial board

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They were also one of the first newsrooms to start working remotely from home. In addition to covering a health pandemic, the news cycle in Seattle has revolved around hefty issues such as politics, wildfires and racial injustice.


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As more papers around the country embrace community funded journalism, the Times has become a model for them to emulate. Recently, the Local Media Association (LMA) announced it was partnering with the Times to develop curriculum for its Lab for Journalism Funding, where 16 publishers will focus on strategies to fund journalism through philanthropy.

In the end, the decision paid off. Fisco shared that the Times currently has about 70,000 digital subscribers; 20,000 of them acquired just in the past six months.


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The primary bile acids chenodeoxycholic acid (CDCA) and cholic acid (CA) are synthesized via two pathways utilizing approximately fifteen enzymes from cholesterol in the liver . The rate-limiting enzyme, cytochrome P450 cholesterol 7α-hydroxylase (CYP7A1), triggers the classical pathway, converting cholesterol into 7α-hydroxycholesterol and producing most of the BA pool . CA is formed through subsequent modification by a series of enzyme cascades (CYP8B1, AKR1D1, AKR1C4, and CYP27A1), while CDCA is synthesized by the same enzyme cascades except for CYP8B1 . The rest of the BA pool is synthesized by cytochrome P450 27α-hydroxylase (CYP27A1) via an alternative pathway. First, cholesterol may be oxidized to 27-hydroxycholesterol with the help of CYP7B1. Then, 27-hydroxycholesterol is transformed into CDCA by CYP7B1 (Figure 1). The dissociative BAs mentioned above transform into conjugated BAs after their conjugation to either glycine (primarily in humans) or taurine (predominantly in mice) by bile acid-amino acid transferase (BAT) and bile acid-CoA synthase (BACS) enzymes. Next, conjugated BAs are secreted into the bile canaliculi via the bile salt export pump and BA transporters MRP2 and MDR1A . Subsequently, they accumulate and are stored and concentrated in the gallbladder. When cholecystokinin (CCK) is secreted by enteroendocrine I cells, the gallbladder is stimulated to contract and secrete bile into the duodenum to participate in the digestion and solubilization of ingested lipids. Approximately 95% of intestinal BAs are reabsorbed by enterocytes from the distal ileum through the apical sodium-dependent BA transporter (ASBT/SLC10A2) or the ileal bile acid transporter (IBAT) [23, 24].


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