These results indicate that LKB1 plays a critical role in bile acid homoeostasis and that lack of LKB1 in the liver results in cholestasis.
Additionally, circulating LDL (low-density lipoprotein)-cholesterol and non-esterified cholesterol levels were increased in LLKB1KO mice with an associated alteration in red blood cell morphology and development of hyperbilirubinaemia. Together, these changes resulted in toxic accumulation of bile salts, reduced liver function and failure to thrive.
Concomitant with this, it was found that the majority of BSEP (bile salt export pump) was retained in intracellular pools rather than localized to the canalicular membrane in hepatocytes from LLKB1KO (liver-specific Lkb1-knockout) mice. We report that liver-specific deletion of LKB1 in mice leads to defective canaliculi and bile duct formation, causing impaired bile acid clearance and subsequent accumulation of bile acids in serum and liver. In the present study, it is shown that hepatic LKB1 plays a key role in liver cellular architecture and metabolism. However, the long-term role of LKB1 in hepatic function is unknown. Note: We do not offer technical support for developing or debugging scripted downloading processes.LKB1 is a ‘master’ protein kinase implicated in the regulation of metabolism, cell proliferation, cell polarity and tumorigenesis. Note that this policy may change as the SEC manages SEC.gov to ensure that the website performs efficiently and remains available to all users. This SEC practice is designed to limit excessive automated searches on SEC.gov and is not intended or expected to impact individuals browsing the SEC.gov website. Once the rate of requests has dropped below the threshold for 10 minutes, the user may resume accessing content on SEC.gov. If a user or application submits more than 10 requests per second, further requests from the IP address(es) may be limited for a brief period. Current guidelines limit users to a total of no more than 10 requests per second, regardless of the number of machines used to submit requests. We reserve the right to block IP addresses that submit excessive requests. To ensure our website performs well for all users, the SEC monitors the frequency of requests for SEC.gov content to ensure automated searches do not impact the ability of others to access SEC.gov content. Unauthorized attempts to upload information and/or change information on any portion of this site are strictly prohibited and are subject to prosecution under the Computer Fraud and Abuse Act of 1986 and the National Information Infrastructure Protection Act of 1996 (see Title 18 U.S.C. For security purposes, and to ensure that the public service remains available to users, this government computer system employs programs to monitor network traffic to identify unauthorized attempts to upload or change information or to otherwise cause damage, including attempts to deny service to users. More Information Internet Security Policyīy using this site, you are agreeing to security monitoring and auditing. For more information, contact more information, please see the SEC’s Web Site Privacy and Security Policy.
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