Treatment of cirrhotic rats with epidermal growth factor and insulin accelerates liver DNA synthesis after partial hepatectomy

“…In the rat, insulin treatment is able to enhance liver regeneration after PH impaired by either ethanol 28 or CCl 4 . 29 Moreover, intraportal insulin injection promotes the recovery of remnant liver functions in hepatectomized patients. 30 The results reported here suggest that FK506 promotes liver regeneration in hepatectomized rats by increasing liver sensitivity to insulin.…”

Section: Discussionmentioning

confidence: 99%

Pretreatment with FK506 up-regulates insulin receptors in regenerating rat liver

et al. 2002

View full text Add to dashboard Cite

This report examines the effect of FK506 pretreatment on liver insulin receptor expression in partially (70%) hepatectomized rats. FK506 pretreatment led to an increased insulin receptor number 24 hours after hepatectomy, detected by means of insulin binding and crosslinking procedures. This increase was related to enhanced insulin receptor expression determined by in vitro mRNA translation and Western blot techniques. We also tested the functionality of the expressed insulin receptors by [ 3 H] thymidine incorporation into DNA in insulin-stimulated hepatocytes. The results show that FK506 pretreatment elicits an increase in the amount of insulin receptor ␣-subunits as measured by Western blot. Maximum ␣-subunit expression recorded 24 hours after surgery was preceded by increased insulin receptor mRNA levels, which were detected 6 hours after hepatectomy. Moreover, in FK506 -pretreated rat hepatocytes, obtained from remnant livers 24 hours after partial hepatectomy (PH), the increase in insulin receptor number was associated with improved sensitivity to the hormone. However, in both experimental groups (FK506-pretreated and nonpretreated rats), the sensitivity of hepatocytes toward epidermal growth factor (EGF) showed no significant change, which suggests a specific effect of FK506 on insulin receptor expression. In conclusion, our findings suggest that FK506 pretreatment induces insulin receptor expression in regenerating rat liver and promotes liver regeneration in hepatectomized rats. (HEPATOLOGY 2002;36:555-561.) P retreatment with immunosuppressive drugs, such as FK506 and cyclosporin A (CsA), increases the liver regenerative response after partial hepatectomy (PH) in rats. 1 Several research efforts have tried to determine the factors involved in the proliferative response associated with drug treatment. FK506 or CsA could modulate the liver response by (1) increasing the expression of local mitogens such as hepatocyte growth factor 2 or insulin-like growth factor I 3 ; (2) decreasing the production of inhibitory cytokines such as transforming growth factor ␤ 1 2 or interleukin 2 4 ; (3) inhibiting natural killer activity 4 ; or (4) predisposing the liver to regenerative signals. This last hypothesis has been suggested but not shown. Insulin is considered a secondary mitogen that enhances liver sensitivity to mitogens during its regeneration. 5 Administering insulin to 70% PH rats increases [ 3 H] thymidine labeling of DNA in hepatic parenchyma cells. 6 Insulin induces a specific peak in [ 3 H] thymidine incorporation 24 hours after PH, which is not observed in insulin-untreated or glucagon-treated animals. 6 This 24-hour period after PH also coincides with maximal effects of FK506 1 or CsA 2 on the liver regenerative response. Moreover, the role of insulin in liver regeneration is supported by its blunting of the immediate-early gene response after PH in diabetic animals. 7 In a very recent study performed in 70% PH/50% pancreatectomized rats, it was shown that liver mass recovery in these animals was del...

show abstract

“…Current potential therapeutic strategies focus on administration of exogeneous hormones, cytokines, growth factors, and chemokines, including EGF, HGF, and vascular endothelial growth factor, and fibroblast growth factor . Preclinical animal experiments suggest that this may stimulate liver regeneration, prevent hepatic failure, and increase postoperative survival .…”

Section: Hallmarks Of Liver Regeneration and The Therapeutic Perspectivementioning

confidence: 99%

Hallmarks of postoperative liver regeneration: An updated insight on the regulatory mechanisms

Shi

Line

2019

J of Gastro and Hepatol

View full text Add to dashboard Cite

Performance and advances in liver surgery makes remarkable progress of the understanding of liver regeneration. Liver regeneration after liver resection has been widely researched, and the underlying mechanism mostly concerns proliferation of hepatocytes and the influence by inflammation through activation of Kupffer cells and the other parenchymal cells, the second regenerative pathway by hepatic progenitor cells (HPCs), inducing angiogenesis, remodeling of a extracellular matrix (ECM), and termination mechanisms. New clinical surgeries and the updated multiomics analysis are exploiting the remarkable progress, especially in immune regulation and metabolic process of two emerging hallmarks. This review briefly represents a systemic outline of eight hallmarks, including hepatocyte proliferation, contribution of hepatic progenitor cells, inducing angiogenesis, reprogramming of the extracellular matrix, apoptosis and termination of proliferation, inflammation, immune and metabolic regulation, which are set as organizing characteristics of postoperative liver regeneration and future directions of refining treatment targets.

show abstract

Treatment of cirrhotic rats with epidermal growth factor and insulin accelerates liver DNA synthesis after partial hepatectomy

Cited by 15 publications

References 19 publications

The mystery of liver regeneration

The mystery of liver regeneration

Pretreatment with FK506 up-regulates insulin receptors in regenerating rat liver

Hallmarks of postoperative liver regeneration: An updated insight on the regulatory mechanisms

Contact Info

Product

Resources

About