REGULATION OF HORMONE-SENSITIVE LIPASE IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

Insulin deficiency as seen in insulin-dependent diabetes mellitus caus es an activation of lipolysis in adipose tissue that results in hydrol ysis of stored triglycerides and release of large amounts of fatty aci ds into the plasma, leading to diabetic ketoacidosis (DKA). Hormone-se nsitive lipase (HSL) is thought to be the rate-limiting enzyme of lipo lysis in adipose tissue. This study was designed to examine the effect s of insulin deficiency on the regulation of HSL in isolated adipocyte s. Insulin deficiency was induced by a single dose of streptozotocin. After 8 days, some animals were treated with insulin, and all animals were killed 10 days after induction of insulin deficiency. Compared wi th levels in control rats, 10 days of insulin deficiency increased HSL activity twofold (P <.05), as assayed for neutral cholesterol esteras e activity, and insulin treatment returned HSL activity to normal. HSL protein was increased twofold (P <.05) in streptozotocin-induced diab etic rats, as estimated by immunoblotting. but remained elevated after insulin treatment. Levels of HSL mRNA assessed by Northern blot analy sis also increased twofold (P <.01) in adipose cells isolated from str eptozotocin-induced diabetic rats. and remained elevated after insulin treatment. In conclusion, our studies suggest that 10 days of insulin deficiency increases HSL expression via pretranslational mechanisms a nd short-term insulin treatment returns HSL activity to normal via pos ttranslational mechanisms in adipose tissue. Copyright (C) 1995 by W.B . Saunders Company