Cellular protein markers, therapeutics, and drug delivery strategies in the treatment of diabetes-associated liver fibrosis

Lin, Chien‐Yu; Adhikary, Pratik; Cheng, Kun

doi:10.1016/j.addr.2021.04.008

Cited by 20 publications

(13 citation statements)

References 179 publications

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“…Moreover, the prevalence of liver fibrosis among patients with both T2D and NAFLD is 17.02% [ 14 ], and the interaction among T2D, NAFLD and liver fibrosis is complicated. Hyperglycemia can induce deleterious effects on liver cells and initiate NAFLD progression from simple steatosis to NASH and fibrosis [ 15 ]; additionally, NAFLD increases the risk of liver fibrosis in T2D patients [ 16 ]. Untreated liver fibrosis will turn into irreversible cirrhosis and HCC, thereby leading to mortality [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

“…Hyperglycemia can induce deleterious effects on liver cells and initiate NAFLD progression from simple steatosis to NASH and fibrosis [ 15 ]; additionally, NAFLD increases the risk of liver fibrosis in T2D patients [ 16 ]. Untreated liver fibrosis will turn into irreversible cirrhosis and HCC, thereby leading to mortality [ 16 ]. Several biochemical parameters and diagnostic panels of liver fibrosis have been evaluated [ 17 , 18 ], and early screening and diagnosis of liver fibrosis in T2D patients with NAFLD could improve the long-term prognosis of patients [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

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The Determinants of Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus

Fang

Hung

et al. 2022

Biomedicines

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Liver fibrosis is a key pathophysiology process in chronic liver disease. It is still unclear whether the impact of liver fibrosis is not fully realized in type 2 diabetes mellitus (T2D) patients with nonalcoholic fatty liver disease (NAFLD), and the factors affecting nonalcoholic steatohepatitis (NASH) or liver stiffness also remain unclear. The aim of this study was to evaluate the determinants of liver fibrosis and in T2D patients with NAFLD. Liver fibrosis and steatosis were measured using transient elastography (FibroScan). Of 226 T2D patients with NAFLD, 50 with liver fibrosis had higher body mass index, serum uric acid, triglyceride and glycated hemoglobin levels and lower high density lipoprotein levels than 176 without liver fibrosis. Multivariate analysis revealed that aging, obesity, sulfonylurea usage and high levels of AST increased the risk of liver fibrosis in T2D patients with NAFLD. Our findings provide useful information to clinical physicians for earlier detection of liver fibrosis in T2D patients with NAFLD and to prevent liver fibrosis through controlling these risk factors.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Determinants of Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus

Fang

Hung

et al. 2022

Biomedicines

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“…In fact, T2DM has been recognized a promoter of liver fibrosis. Though the underlying mechanisms remain largely unknown, insulin resistance and hyperglycemia may contribute to liver fibrosis in T2DM patients ( 19 , 20 ).…”

Section: Discussionmentioning

confidence: 99%

Association between use of liraglutide and liver fibrosis in patients with type 2 diabetes

et al. 2022

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ObjectivePatients with type 2 diabetes have a high risk of non-alcoholic fatty liver disease (NAFLD) and related liver fibrosis. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated efficacy in improving NAFLD, while their effectiveness on liver fibrosis is limited in type 2 diabetic patients.Materials/MethodsA prospective cohort study was performed in type 2 diabetic patients. The study subjects were divided into two groups based on the use of liraglutide or not, and propensity score matching (PSM) was also conducted. After 12 months follow-up, liver fibrosis was assessed by NAFLD fibrosis score (NFS) fibrosis-4 (FIB-4), and liver stiffness measurement (LSM). The association between liraglutide use and liver fibrosis was analyzed by multivariable linear regression.ResultsIn the current study, a total of 1,765 type 2 diabetic patients were enrolled. 262 patients were liraglutide user and 1,503 were nouser. After 12 months follow-up, liraglutide use tended to be associated with reduced prevalence of advanced fibrosis (3.1% vs. 6.1%, P = 0.218). After adjustment for confounding factors, multivariable linear regression revealed that liraglutide use was negatively associated with decreased NFS (β= -0.34, P = 0.043), FIB4 (β= -0.26, P = 0.044) and LSM (β= -4.95, P = 0.007) in type 2 diabetics. The results after PSM were similar to those before PSM.ConclusionsLiraglutide treatment is associated with decreased liver fibrosis in type 2 diabetic subjects.

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“…Numerous studies have shown that the expression of NF-κB is upregulated in the liver after the induction of diabetes, indicating that inflammation-related pathways are involved in STZ-induced diabetes [ 37 , 38 ]. A recent review has also determined that some antidiabetic drugs used in the treatment of liver fibrosis are also involved in downregulating the expression of NF-κB [ 3 ]. Moreover, there is emerging evidence indicating that SIRT1 deacetylates NF-κB [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…Type 2 diabetes mellitus (T2DM) is a well-known chronic metabolic disease [ 1 ], and diabetic liver injury is one of its complications, which can seriously affect the quality of life of diabetic patients through dysregulation of glucose and lipid metabolism [ 2 , 3 ]. When adipocytes accumulate in the liver due to disorders of lipid metabolism, the liver develops insulin resistance which, in turn, leads to hyperglycemia and glucose metabolism disorders.…”

Section: Introductionmentioning

confidence: 99%

Effects of Rice-Husk Silica Liquid in Streptozotocin-Induced Diabetic Mice

et al. 2022

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Type 2 diabetes mellitus is a complex multifactorial disease characterized by poor glucose tolerance and insulin resistance. Rice-husk silica liquid (RHSL) derived from rice husk has the ability to improve the dysfunction of pancreatic β-cells. This study aimed to confirm the potential protective effects of RHSL in streptozotocin (STZ)-induced diabetic mice. Diabetes was induced in male C57BL/6J mice by intraperitoneal administration of STZ (200 mg/kg BW). RHSL, food-grade silica liquid (FDSL), and rosiglitazone (RSG) were administered to diabetic mice for 12 weeks after successful induction of diabetes. During the experiment, fasting blood glucose, serum insulin, and organ weights were measured. The histopathology of liver tissue was evaluated by H&E staining. Western blotting was performed to assess protein expression levels. The results showed that RHSL significantly reversed the serum insulin levels and improved oral glucose tolerance test (OGTT) results (p < 0.05). In addition, liver sections of STZ-induced diabetic mice after RHSL treatment showed neatly arranged and intact hepatocytes. Furthermore, RHSL was more effective than FDSL in increasing the expression of SIRT1 and decreasing the expression of the PPAR-γ and p-NF-κB proteins. Taken together, this study demonstrated that RHSL ameliorated STZ-induced insulin resistance and liver tissue damage in C57BL/6J mice.

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Cellular protein markers, therapeutics, and drug delivery strategies in the treatment of diabetes-associated liver fibrosis

Cited by 20 publications

References 179 publications

The Determinants of Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus

The Determinants of Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus

Association between use of liraglutide and liver fibrosis in patients with type 2 diabetes

Effects of Rice-Husk Silica Liquid in Streptozotocin-Induced Diabetic Mice

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