Pancreatogenic diabetes: Triggering effects of alcohol and HIV

Moses New-Aaron, Murali Ganesan, Raghubendra Singh Dagur, Kusum K. Kharbanda, Larisa Y. Poluektova, Natalia A. Osna

Research output: Contribution to journalReview articlepeer-review

Abstract

Multiorgan failure may not be completely resolved among people living with HIV despite HAART use. Although the chances of organ dysfunction may be relatively low, alcohol may potentiate HIV-induced toxic effects in the organs of alcohol-abusing, HIV-infected individuals. The pancreas is one of the most implicated organs, which is manifested as diabetes mellitus or pancreatic cancer. Both alcohol and HIV may trigger pancreatitis, but the combined effects have not been explored. The aim of this review is to explore the literature for understanding the mechanisms of HIV and alcoholinduced pancreatotoxicity. We found that while premature alcohol-inducing zymogen activation is a known trigger of alcoholic pancreatitis, HIV entry through C-C chemokine receptor type 5(CCR5)into pancreatic acinar cells may also contribute to pancreatitis in people living with HIV (PLWH). HIV proteins induce oxidative and ER stresses, causing necrosis. Furthermore, infiltrative immune cells induce necrosis on HIV-containing acinar cells. When necrotic products interact with pancreatic stellate cells, they become activated, leading to the release of both inflammatory and profibrotic cytokines and resulting in pancreatitis. Effective therapeutic strategies should block CCR5 and ameliorate alcohol’s effects on acinar cells.

Original languageEnglish (US)
Article number108
Pages (from-to)1-25
Number of pages25
JournalBiology
Volume10
Issue number2
DOIs
StatePublished - Feb 2021

Keywords

  • Diabetes mellitus
  • Ethanol metabolites
  • HIV
  • Pancreatic acinar cells
  • Pancreatic stellate cells
  • Pancreatitis
  • Pancreatotoxicity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

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