Fat-induced liver insulin resistance

Pankaj Shah, Ananda Basu, Robert Rizza

Research output: Contribution to journalReview articlepeer-review

16 Scopus citations


In vitro studies have established that free fatty acids (FFAs) are important regulators of hepatic glucose metabolism. FFAs can increase hepatic glucose release by increasing the amount and activity of glucose-6-phosphatase and multiple gluconeogenic enzymes. Elevated FFAs can also potentially decrease hepatic glucose uptake by decreasing hepatic glucokinase activity. In vivo studies in both animals and humans have shown a close correlation between changes in plasma FFAs and endogenous glucose production (EGP). Intervention studies have established that changes in plasma FFAs are accompanied by changes in the relative contribution of gluconeogenesis and glycogenolysis to EGP. The effects of a change in FFAs on EGP itself are more evident when compensatory changes in insulin secretion are prevented or when insulin secretion is impaired (eg, diabetes mellitus). The effects of elevated FFAs on splanchnic glucose uptake are less clear, in that they appear to have no effect in nondiabetic humans and may impair uptake in people with type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)214-218
Number of pages5
JournalCurrent diabetes reports
Issue number3
StatePublished - Jun 2003

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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