Therapeutic targets, novel drugs, and delivery systems for diabetes associated NAFLD and liver fibrosis

Virender Kumar, Xiaofei Xin, Jingyi Ma, Chalet Tan, Natalia Osna, Ram I. Mahato

Research output: Contribution to journalReview articlepeer-review

25 Scopus citations

Abstract

Type 2 diabetes mellitus (T2DM) associated non-alcoholic fatty liver disease (NAFLD) is the fourth-leading cause of death. Hyperglycemia induces various complications, including nephropathy, cirrhosis and eventually hepatocellular carcinoma (HCC). There are several etiological factors leading to liver disease development, which involve insulin resistance and oxidative stress. Free fatty acid (FFA) accumulation in the liver exerts oxidative and endoplasmic reticulum (ER) stresses. Hepatocyte injury induces release of inflammatory cytokines from Kupffer cells (KCs), which are responsible for activating hepatic stellate cells (HSCs). In this review, we will discuss various molecular targets for treating chronic liver diseases, including homeostasis of FFA, lipid metabolism, and decrease in hepatocyte apoptosis, role of growth factors, and regulation of epithelial-to-mesenchymal transition (EMT) and HSC activation. This review will also critically assess different strategies to enhance drug delivery to different cell types. Targeting nanocarriers to specific liver cell types have the potential to increase efficacy and suppress off-target effects.

Original languageEnglish (US)
Article number113888
JournalAdvanced Drug Delivery Reviews
Volume176
DOIs
StatePublished - Sep 2021

Keywords

  • Cirrhosis
  • Diabetes
  • Hepatocellular carcinoma
  • Inflammation
  • Liver fibrosis
  • NAFLD

ASJC Scopus subject areas

  • Pharmaceutical Science

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