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Hepatogenous Diabetes Treatment

Diagnostic Significance Of Diabetes In Liver Cirrhosis

Diagnostic Significance Of Diabetes In Liver Cirrhosis

Diagnostic significance of diabetes in liver cirrhosis Abstract: Alterations in carbohydrate metabolism are frequently observed in cirrhosis, and approximately 15% to 30% of patients have overt diabetes. The aim of the present study was to examine the clinical implications and the prognostic significance of hepatogenous diabetes in patients with liver cirrhosis. In a retrospective and prospective study in cirrhosis; we analyzed the prognostic significance of diabetes, which was defined as the presence of hyperglycemia and overt glycosuria that in most cases required dietary restrictions or active treatment. The prospective cohort study was conducted in 76 patients with histologically confirmed liver cirrhosis. The examination included a history, determination of basal C-peptide and glycosylated hemoglobin (HbA1c) and, in some cases, a 3 hours oral glucose tolerance test with 100 g glucose. The clinical records of all patients with cirrhosis admitted to Govt City Hospital, Bilaspur and CIMS, Bilaspur for the period 2011 to 2016 were reviewed in 2016 and surviving patients were prospectively followed up until December 2016. Final status could be obtained in 76 (41 with diabetes); 63 were alive at the end of follow-up. The model identified, in sequence, albumin, ascites, age, bilirubin, serum Glucose and platelets as prognostic factors. The larger mortality rate in patients with diabetes was not due to complications of diabetes but to an increased risk of hepatocellular failure. Thus, the presence of diabetes, clinically detectable and often requiring adequate treatment is a risk factor for long-term survival in cirrhosis. Fifty Four percent of patients with liver cirrhosis had manifest diabetes, 41% had impaired glucose tolerance and only 5% had normal glucose tolerance. Continue reading >>

[metabolic Disturbances In Liver Cirrhosis (part 2), Hepatogenous Diabetes: Diagnostic Aspects And Treatment].

[metabolic Disturbances In Liver Cirrhosis (part 2), Hepatogenous Diabetes: Diagnostic Aspects And Treatment].

A comment on this article appears in " [Metabolic disturbances in liver cirrhosis: hepatogenous diabetes]. " Dtsch Med Wochenschr. 2010 Apr;135(14):716; author reply 716. Uip to 20% of patients with liver cirrhosis develop hepatogenous diabetesdue to the hepatocellular functional loss and insulin resistance. Optimizing diabetic metabolic conditions is not only important to avoid typical late complications of diabetes, but also cirrhosis-associated complications e.g. gastrointestinal bleeding, hepatic encephalopathy or the occurence of hepatocellular carcinoma. So far there have beenno recommendations orguidelines for the diagnosis and treatmentof hepatogenous diabetes. The medical teatment of a diabetic condition is mainly influenced by its side effects. The risk of hypoglycemia must be considered carefully during drug treatment, especially in patients with chronic alcohol abuse. Suitable oral antidiabetics are glinides and short-acting sulfonylureas or possibly meal-related insulin administration with short-acting insulins or rapid-acting insulin analogues. Biguanide and PPAR-gamma agonists are contraindicated because of side effects in liver cirrhosis. Regarding basic treatment, an adequate daily energy and protein supply should be ensuredbecause the majority of patients with liver cirrhosis are malnourished. Continue reading >>

Cn105194562a - Medicament For Treating Hepatogenous Diabetes - Google Patents

Cn105194562a - Medicament For Treating Hepatogenous Diabetes - Google Patents

CN105194562A - Medicament for treating hepatogenous diabetes - Google Patents Medicament for treating hepatogenous diabetes CN105194562A CN 201510700601 CN201510700601A CN105194562A CN 105194562 A CN105194562 A CN 105194562A CN 201510700601 CN201510700601 CN 201510700601 CN 201510700601 A CN201510700601 A CN 201510700601A CN 105194562 A CN105194562 A CN 105194562A Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.) The invention relates to a medicament for treating hepatogenous diabetes. The medicament is prepared from the following active pharmaceutical ingredients in parts by weight: 15 to 25 parts of phyllanthus urinaria, 15 to 25 parts of curcuma longa, 25 to 50 parts of cacumen platycladi, 20 to 35 parts of radix lithospermi, 10 to 20 parts of rhizome chuanxiong, 10 to 20 parts of semen lepidii, 10 to 15 parts of hairyvein agrimonia herb, 10 to 15 parts of psoralea corylifolia, 10 to 15 pats of black nightshade, 10 to 15 parts of medlar, 10 to 15 parts of rhizoma atractylodis, 10 to 20 parts of radix astragali, 5 to 10 parts of radix sophorae subprostrata, 5 to 10 parts of pseudobulbus cremastrae seu pleiones, 5 to 10 parts of peach kernel, 5 to 10 parts of rosa laevigata michx, 5 to 10 parts of clematis chinensis, 5 to 10 parts of herba portulacae, 10 to 25 parts of polygonum cuspidatum and 10 to 20 parts of semen raphani. The medicament has the efficacies of discharging liver and relieving depression, promoting the production of body fluid to relieve thirst, activating blood to remove stasis, clearing away heat and toxic materials, strengthening the body resistance and tonifying qi, and improving the immunity, is used for tre

[hepatogenous Diabetes - Diagnostics And Treatment].

[hepatogenous Diabetes - Diagnostics And Treatment].

II. Medizinische Abteilung, Stdtisches Krankenhaus Mnchen-Bogenhausen. [email protected] Z Gastroenterol. 2009 May;47(5):436-45. doi: 10.1055/s-0028-1109200. Epub 2009 May 5. BACKGROUND: Patients with liver cirrhosis develop frequently disturbances of glucose metabolism e. g. glucose intolerance or hepatogenous diabetes which are caused by the hepatocellular functional loss and insulin resistance due to chronic liver disease. DISCUSSION: Until now there are no recommendations comparable to guidelines on the diagnosis of and therapy for hepatogenic diabetes. Regarding basic treatment a sufficient daily energy and protein supply should be guaranteed since the majority of patients with liver cirrhosis are malnourished. The risk of hypoglycaemia must be considered carefully under pharmacological treatment of hepatogenous diabetes. Biguanide and PPAR gamma agonists are contraindicated due to side effects in liver cirrhosis. Suitable oral antidiabetics are glinides and short-acting sulfonylureas. If a sufficient diabetes adjustment does not succeed by oral antidiabetics a prandial insulin therapy using short-acting insulins or rapid-acting insulin analogues should be applied. CONCLUSION: Optimisation of diabetic metabolic conditions is not only important to avoid typical diabetic late complications but also cirrhosis-associated complications, e. g., gastrointestinal bleeding, hepatic encephalopathy or the occurrence of hepatocellular carcinoma. Continue reading >>

[hepatogenous Diabetes - Diagnostics And Treatment].

[hepatogenous Diabetes - Diagnostics And Treatment].

Patients with liver cirrhosis develop frequently disturbances of glucose metabolism e. g. glucose intolerance or hepatogenous diabetes which are caused by the hepatocellular functional loss and insulin resistance due to chronic liver disease.Until now there are no recommendations comparable to guidelines on the diagnosis of and therapy for hepatogenic diabetes. Regarding basic treatment a sufficient daily energy and protein supply should be guaranteed since the majority of patients with liver cirrhosis are malnourished. The risk of hypoglycaemia must be considered carefully under pharmacological treatment of hepatogenous diabetes. Biguanide and PPAR gamma agonists are contraindicated due to side effects in liver cirrhosis. Suitable oral antidiabetics are glinides and short-acting sulfonylureas. If a sufficient diabetes adjustment does not succeed by oral antidiabetics a prandial insulin therapy using short-acting insulins or rapid-acting insulin analogues should be applied.Optimisation of diabetic metabolic conditions is not only important to avoid typical diabetic late complications but also cirrhosis-associated complications, e. g., gastrointestinal bleeding, hepatic encephalopathy or the occurrence of hepatocellular carcinoma. Der hepatogene Diabetes - aktueller Stand der Diagnostik und Therapie Do you want to read the rest of this article? ... The hepatogenous diabetes is developed by about 30% chronic liver disease patients. There are other studies conducted about Hepatogenous diabetes [19][20][21][22] Continue reading >>

Hepatogenous Diabetes: Is It A Neglected Condition In Chronic Liver Disease?

Hepatogenous Diabetes: Is It A Neglected Condition In Chronic Liver Disease?

Hepatogenous diabetes: Is it a neglected condition in chronic liver disease? Diego Garca-Compen , Jos Alberto Gonzlez-Gonzlez , Fernando Javier Lavalle-Gonzlez , Emmanuel Irineo Gonzlez-Moreno , Jess Zacaras Villarreal-Prez , and Hctor Jess Maldonado-Garza Diego Garca-Compen, Jos Alberto Gonzlez-Gonzlez, Emmanuel Irineo Gonzlez-Moreno, Hctor Jess Maldonado-Garza, Gastroenterology Service and Department of Internal Medicine, University Hospital Dr. Jos E. Gonzlez and Medical School, Universidad Autnoma de Nuevo Len, Monterrey 64320, Mxico Fernando Javier Lavalle-Gonzlez, Jess Zacaras Villarreal-Prez, Endocrinology Service and Department of Internal Medicine, University Hospital Dr. Jos E. Gonzlez and Medical School, Universidad Autnoma de Nuevo Len, Monterrey 64320, Mxico Author contributions: All the authors contributed equally to the revision of the content of this manuscript; and Garca-Compen D conceived and wrote the editorial. Correspondence to: Diego Garca-Compen, MD, MMSc, Gastroenterology Service and Department of Internal Medicine, University Hospital Dr. Jos E. Gonzlez and Medical School, Universidad Autnoma de Nuevo Len, Madero y Gonzalitos S/N, Monterrey 64320, Mxico. [email protected] Telephone: +52-81-83487315 Fax: +52-81-89891381 Received 2015 Dec 23; Revised 2016 Jan 20; Accepted 2016 Feb 20. Copyright The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved. This article has been cited by other articles in PMC. Diabetes mellitus (DM) that occurs because of chronic liver disease (CLD) is known as hepatogenous diabetes (HD). Although the association of diabetes and liver cirrhosis was described forty years ago, it was scarcely studied for long time. Patients suffering from this condition have low frequency of risk Continue reading >>

Diabetes In Chronic Liver Disease

Diabetes In Chronic Liver Disease

Researchers in Vienna have made a breakthrough with synthetic bile acids in the treatment of primary sclerosing cholangitis. These compounds could feasibly be of use in fatty liver and diabetes – but would require further study. “Bile acids are not only involved in the secretion of bile fluids and fat digestion, but also have hormone-like effects, particularly on the regulation of fat and glucose metabolism in the liver. Researchers at the MedUni Vienna are currently also investigating what role these effects of Nor-Urso [norursodeoxycholic acid] and other bile acid derivatives play in the treatment of fatty liver, diabetes, fat metabolism problems and arteriosclerosis and how they could replace current conventional treatment methods and drugs.” This news is interesting and it reminds us of the strong link between diabetes and the liver. What is this relationship and what are the implications for clinical practice? The liver plays an important role in the regulation of glucose homeostasis. This helps explain why glucose intolerance is a feature or complication of chronic liver disease and cirrhosis. Liver disease associated with diabetes mellitus can be divided into three groups as shown below [1]: 1. Liver disease occurring as a consequence of diabetes mellitus • Glycogen deposition • Steatosis and nonalcoholic steatohepatitis (NASH) • Fibrosis and cirrhosis • Biliary disease, cholelithiasis, cholecystitis • Complications of therapy of diabetes (cholestatic and necroinflammatory) 2 . Diabetes mellitus and abnormalities of glucose homeostasis occurring as a complication of liver disease • Hepatitis • Cirrhosis • Hepatocellular carcinoma • Fulminant hepatic failure • Postorthotopic liver transplantation 3 . Liver disease occurring coincidentally Continue reading >>

A Synthetic-biology-inspired Therapeutic Strategy For Targeting And Treating Hepatogenous Diabetes Mendeley Csv Ris Bibtex

A Synthetic-biology-inspired Therapeutic Strategy For Targeting And Treating Hepatogenous Diabetes Mendeley Csv Ris Bibtex

A Synthetic-Biology-Inspired Therapeutic Strategy for Targeting and Treating Hepatogenous Diabetes American Society of Gene and Cell Therapy A Synthetic-Biology-Inspired Therapeutic Strategy for Targeting and Treating Hepatogenous Diabetes ETH Zrich::00002 - ETH Zrich::00012 - Lehre und Forschung::00007 - Departemente::02060 - Departement Biosysteme / Department of Biosystems Science and Engineering::03694 - Fussenegger, Martin ETH Zrich::00002 - ETH Zrich::00012 - Lehre und Forschung::00007 - Departemente::02060 - Departement Biosysteme / Department of Biosystems Science and Engineering::03694 - Fussenegger, Martin ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.atitle=A%20Synthetic-Biology-Inspired%20Therapeutic%20Strategy%20for%20Targeting%20and%20Treating%20Hepatogenous%20Diabetes&rft.jtitle=Molecular%20therapy&rft.date=2017-02&rft.volume=25&rft.issue=2&rft.spage=443&rft.epage=455&rft.issn=1525-0016&1525-0024&rft.au=Xue,%20Shuai&Yin,%20Jianli&Shao,%20Jiawei&Yu,%20Yuanhuan&Yang,%20Linfeng&rft.genre=article&rft_id=info:doi/10.1016/j.ymthe.2016.11.008 Continue reading >>

Diabetes And Liver An Association: Hepatogenous Diabetes Mechanism And Some Evidences

Diabetes And Liver An Association: Hepatogenous Diabetes Mechanism And Some Evidences

Ajita Acharya, Eden Wudneh, Radhika Krishnan, Aisha Ashraf and Hassaan Tohid* California Institute of Behavioral Neurosciences and Psychology (The Neuro/Cal Institute), University of California, Davis, USA *Corresponding Author: Tohid H, California Institute of Behavioral Neurosciences and Psychology (The Neuro-Cal Institute), 4751 Mengels Blvd, Fairfield, California, 94534, USA, Tel: 707-999-1268; E-mail: [email protected] Citation: Acharya A, Wudneh E, Krishnan R, Ashraf A, Tohid H (2016) Diabetes and Liver an Association: Hepatogenous Diabetes Mechanism and Some Evidences. J Cell Sci Ther 7:257. doi: 10.4172/2157-7013.1000257 Copyright: © 2016 Acharya A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Visit for more related articles at Journal of Cell Science & Therapy Abstract A literature search was conducted in different databases to study the topic of liver problems and diabetes. The aim of the study was to explore more about an association of diabetes mellitus with the liver. The study shows that diabetes does indeed have an effect on liver. Similarly, liver problems like chronic liver disease lead to diabetes which is known as hepatogenous diabetes. Common liver problems seen in diabetes patients include but not limited to fatty liver, decreased glycogen levels, risk of liver cancer etc. Like any medical problem, any knowledge about any subject is never enough, therefore we recommend more studies in the near future to broaden our understanding about the association of the liver with diabetes. Keywords Diabetes; Diabetes complications; Diabetes and liver; Diabete Continue reading >>

A Different Perspective For Management Of Diabetes Mellitus: Controlling Viral Liver Diseases

A Different Perspective For Management Of Diabetes Mellitus: Controlling Viral Liver Diseases

A Different Perspective for Management of Diabetes Mellitus: Controlling Viral Liver Diseases Correspondence should be addressed to Huichun Xing ; [email protected] Received 1 December 2016; Revised 21 January 2017; Accepted 30 January 2017; Published 2 March 2017 Copyright 2017 Yingying Zhao and Huichun Xing. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Knowing how to prevent and treat diabetes mellitus (DM) earlier is essential to improving outcomes. Through participating in synthesis and catabolism of glycogen, the liver helps to regulate glucose homeostasis. Viral related liver diseases are associated with glycometabolism disorders, which means effective management of viral liver diseases may be a therapeutic strategy for DM. The present article reviews the correlation between DM and liver diseases to give an update of the management of DM rooted by viral liver diseases. Insulin deficiency and/or insulin resistance, which causes glycometabolism disorders, leads to the symptoms of diabetes mellitus (DM). DM is an increasingly recognized global health concern. By 2030, the prevalence of diabetes among adults is expected to rise from 6.4% to 7.7% worldwide. During the next decade, the number of adults with diabetes is expected to rise by 20% in developed nations and 69% in developing nations [ 1 , 2 ]. Long-term complications of DM include micro- and macrovascular damage, which include dysfunction of eyes, kidneys, nerves, gastrointestinal tracts, hearts, and blood vessels. Serious illness or stress can result in acute metabolic disorders, such as diabetic ketoacidosis (DKA) and hyperglycemic hyperosm Continue reading >>

Hepatogenous Diabetes. Current Views Of An Ancient Problem.

Hepatogenous Diabetes. Current Views Of An Ancient Problem.

Hepatogenous diabetes. Current views of an ancient problem. Department of Gastroenterology, Hospital Universitario. Ave. Madero y Gonzalitos, Col. Mitras Centro, Monterrey 64700, Mexico. [email protected] Diabetes developed as a complication of cirrhosis is known as hepatogenous diabetes>> (HD). Around 30% to 60% of cirrhotic patients suffer from this metabolic disorder. Insulin resistance in muscular, hepatic and adipose tissues as well as hyperinsulinemia, seem to be pathophysiologic bases for HD. An impaired response of the islet ss-cells of the pancreas and the hepatic insulin resistance are also contributing factors. Diabetes develops when defective oxidative and nonoxidative muscle glucose metabolism develops. Non-alcoholic fatty liver disease (NAFLD), alcoholic cirrhosis, chronic hepatitis C (CHC), and hemochromatosis are more frequently associated with HD. HD in early cirrhosis stages may be sub clinical. Only insulin resistance and glucose intolerance may be observed. As liver disease advances, diabetes becomes clinically manifest, therefore HD may be considered as a marker for liver function deterioration. HD is clinically different from that of type 2 DM since it is less frequently associated with microangiopathy and patients suffer complications of cirrhosis more frequently as well as increased mortality. Insulin resistance and HD associate to a decrease in the sustained response to antiviral therapy and an increased progression of fibrosis in patients with CHC. Diabetes treatment is complex due to liver damage and hepatotoxicity of oral hypoglycemic drugs that are frequently prescribed to these patients. This paper will review current concepts in relation to the pathopysiology, the impact on the clinical outcome of cirrhosis, and the therapy o Continue reading >>

Relationships Between Mean Plasma Glucose And Hba1c In Cirrhotic Patients With Hepatogenous Diabetes

Relationships Between Mean Plasma Glucose And Hba1c In Cirrhotic Patients With Hepatogenous Diabetes

You have reached the maximum number of saved studies (100). Please remove one or more studies before adding more. Relationships Between Mean Plasma Glucose and HbA1c in Cirrhotic Patients With Hepatogenous Diabetes The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. ClinicalTrials.gov Identifier: NCT02325622 Verified December 2014 by Moon Young Kim, Yonsei University. Information provided by (Responsible Party): Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information The liver plays a crucial role in physiological glycemic control through its involvement in several glucose metabolism processes, including glycogenogenesis and glycogenolysis. Liver diseases result in impaired glucose metabolism due to hepatocyte dysfunction, termed as "hepatogenous diabetes". Abnormal glucose metabolism is found in over 90% of patients with liver cirrhosis. and clinically significant diabetes is known to occur in 30% to 70% of the patients. A cohort study of cirrhotic patients with hepatogenous diabetes reported a relatively low diabetic complication rate, and the majority of mortality causes were complications related to liver cirrhosis; furthermore, mortality rate due to diabetic complications were reported to be low. Nonetheless, the average survival rate following the diagnosis of liver cirrhosis is rising due to increasing early detection rate and improvements in treatment modalities, and such rise in survival is expected to result in increased prevalence of hepatogenous diabetes and its complications. Therefore, it is necessary to formula Continue reading >>

Clinical Implications Of Hepatogenous Diabetes In Liver Cirrhosis

Clinical Implications Of Hepatogenous Diabetes In Liver Cirrhosis

Clinical implications of hepatogenous diabetes in liver cirrhosis Andreas Holstein, S Hinze, E Thiessen, A Plaschke, E-H Egberts Journal of Gastroenterology and Hepatology 2002, 17 (6): 677-81 BACKGROUND: Hepatogenous diabetes is a common complication of liver cirrhosis. The aim of the present study was to examine the clinical and therapeutic implications and the prognostic significance of hepatogenous diabetes in patients with liver cirrhosis. METHODS: The prospective cohort study was conducted in 52 patients with histologically confirmed liver cirrhosis (44% Child A, 37% Child B, 19% Child C). The examination included a history, determination of basal C-peptide and glycosylated hemoglobin (HbA(1c)) and, in some cases, a 3 h oral glucose tolerance test with 100 g glucose. Patients were also examined for signs of diabetic retinopathy and information on the further course of illness was obtained. RESULTS: Seventy-one percent of patients with liver cirrhosis had manifest diabetes, 25% had impaired glucose tolerance and only 4% had normal glucose tolerance. In most cases, the hepatogenous diabetes was clinically asymptomatic. Sixteen percent of patients with hepatogenous diabetes had a family history of diabetes; only 8% had retinopathic complications. Within 5.6 +/- 4.5 years after diagnosis of liver cirrhosis, 52% of the diabetics had died, mainly of complications of the cirrhosis. There were no diabetes-associated or cardiovascular deaths. CONCLUSIONS: Hepatogenous diabetes differs from type 2 diabetes in that there is less often a positive family history and that the cardiovascular and retinopathic risk is low. The prognosis of cirrhotic patients with diabetes is more likely to be negatively affected by the underlying hepatic disease and its complications than by the Continue reading >>

A Synthetic-biology-inspired Therapeutic Strategy For Targeting And Treating Hepatogenous Diabetes

A Synthetic-biology-inspired Therapeutic Strategy For Targeting And Treating Hepatogenous Diabetes

A Synthetic-Biology-Inspired Therapeutic Strategy for Targeting and Treating Hepatogenous Diabetes Yidan Wang - East China Normal University Mingqi Xie - East China Normal University, Swiss Federal Institute of Technology in Zurich Martin Fussenegger - Swiss Federal Institute of Technology in Zurich Hepatogenous diabetes is a complex disease that is typified by the simultaneous presence of type 2 diabetes and many forms of liver disease. The chief pathogenic determinant in this pathophysiological network is insulin resistance (IR), an asymptomatic disease state in which impaired insulin signaling in target tissues initiates a variety of organ dysfunctions. However, pharmacotherapies targeting IR remain limited and are generally inapplicable for liver disease patients. Oleanolic acid (OA) is a plant-derived triterpenoid that is frequently used in Chinese medicine as a safe but slow-acting treatment in many liver disorders. Here, we utilized the congruent pharmacological activities of OA and glucagon-like-peptide 1 (GLP-1) in relieving IR and improving liver and pancreas functions and used a synthetic-biology-inspired design principle to engineer a therapeutic gene circuit that enables a concerted action of both drugs. In particular, OA-triggered short human GLP-1 (shGLP-1) expression in hepatogenous diabetic mice rapidly and simultaneously attenuated many disease-specific metabolic failures, whereas OA or shGLP-1 monotherapy failed to achieve corresponding therapeutic effects. Collectively, this work shows that rationally engineered synthetic gene circuits are capable of treating multifactorial diseases in a synergistic manner by multiplexing the targeting efficacies of single therapeutics. National Natural Science Foundation of China Ministry of Science and Technology Continue reading >>

A Synthetic-biology-inspired Therapeutic Strategy For Targeting And Treating Hepatogenous Diabetes - Sciencedirect

A Synthetic-biology-inspired Therapeutic Strategy For Targeting And Treating Hepatogenous Diabetes - Sciencedirect

A Synthetic-Biology-Inspired Therapeutic Strategy for Targeting and Treating Hepatogenous Diabetes Hepatogenous diabetes is a complex disease that is typified by the simultaneous presence of type 2 diabetes and many forms of liver disease. The chief pathogenic determinant in this pathophysiological network is insulin resistance (IR), an asymptomatic disease state in which impaired insulin signaling in target tissues initiates a variety of organ dysfunctions. However, pharmacotherapies targeting IR remain limited and are generally inapplicable for liver disease patients. Oleanolic acid (OA) is a plant-derived triterpenoid that is frequently used in Chinese medicine as a safe but slow-acting treatment in many liver disorders. Here, we utilized the congruent pharmacological activities of OA and glucagon-like-peptide 1 (GLP-1) in relieving IR and improving liver and pancreas functions and used a synthetic-biology-inspired design principle to engineer a therapeutic gene circuit that enables a concerted action of both drugs. In particular, OA-triggered short human GLP-1 (shGLP-1) expression in hepatogenous diabetic mice rapidly and simultaneously attenuated many disease-specific metabolic failures, whereas OA or shGLP-1 monotherapy failed to achieve corresponding therapeutic effects. Collectively, this work shows that rationally engineered synthetic gene circuits are capable of treating multifactorial diseases in a synergistic manner by multiplexing the targeting efficacies of single therapeutics. Continue reading >>

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