Downregulation of islet hormone-sensitive lipase during long-term high-fat feeding

Biochem Biophys Res Commun. 2003 May 2;304(2):273-8. doi: 10.1016/s0006-291x(03)00552-7.


Lipid accumulation in pancreatic beta-cells during high-fat (HF) feeding may be involved in inducing a defective insulin secretion due to lipotoxicity. Hormone-sensitive lipase (HSL) is expressed and active in beta-cells, but its importance for islet dysfunction during the development of type 2 diabetes is not known. In this study, prolonged HF feeding of C57BL/6J mice, resulted in decreased HSL expression in islets, representing only 25+/-4% of the levels observed in controls. This was paralleled by triglyceride accumulation and blunted insulin secretion both in vivo and in vitro. After switching the HF diet to a LF diet, HSL expression increased 10-fold compared to the HF fed mice. This was accompanied by reduced triglyceride levels and a restored insulin secretion. These results support the notion that HSL plays a critical role in the regulation of intracellular triglyceride levels in beta-cells, and that downregulation of the enzyme may serve to protect against fatty acid-induced islet dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Cells, Cultured
  • Diabetes Mellitus, Type 2 / enzymology*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diet, Fat-Restricted
  • Down-Regulation*
  • Fats / administration & dosage
  • Fats / pharmacology*
  • Female
  • Glucose Tolerance Test
  • Insulin / metabolism
  • Insulin Resistance
  • Insulin Secretion
  • Islets of Langerhans / enzymology*
  • Islets of Langerhans / metabolism
  • Kinetics
  • Mice
  • Mice, Inbred C57BL
  • Obesity / etiology
  • Sterol Esterase / metabolism*
  • Triglycerides / biosynthesis


  • Fats
  • Insulin
  • Triglycerides
  • Sterol Esterase