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Does the insulin-mimetic action of vanadate involve insulin receptor kinase?

S Pugazhenthi1, R L Khandelwal

  • 1Department of Biochemistry, University of Saskatchewan, Saskatoon, Canada.

Molecular and Cellular Biochemistry
|November 1, 1993
PubMed

Insights

Sodium orthovanadate normalized blood glucose in diabetic rats by enhancing insulin receptor function. This suggests vanadate

Area of Science:

  • Biochemistry
  • Endocrinology
  • Pharmacology

Background:

  • Diabetes mellitus is characterized by hyperglycemia and altered insulin signaling.
  • Streptozotocin-induced diabetes in rats shows increased hepatic insulin receptors but reduced receptor activity.
  • Insulin receptor autophosphorylation and tyrosine kinase activity are impaired in diabetes.

Purpose of the Study:

  • To investigate the effects of vanadate administration on insulin receptor status in diabetic rat livers.
  • To determine if vanadate can ameliorate diabetes-induced changes in insulin receptor function.
  • To explore the role of the insulin receptor in vanadate's insulin-mimetic actions.

Main Methods:

  • Induction of diabetes in rats using streptozotocin.
  • Administration of sodium orthovanadate to diabetic rats.
  • Measurement of plasma glucose, insulin levels, hepatic insulin receptor number, and insulin receptor kinase activity.
  • In vitro studies on vanadate's effect on isolated insulin receptors.

Main Results:

  • Vanadate treatment normalized plasma glucose levels in diabetic rats without altering insulin levels.
  • Insulin-stimulated phosphorylation of the insulin receptor beta subunit significantly increased after vanadate treatment.
  • In vitro, vanadate inhibited insulin receptor dephosphorylation and enhanced tyrosine kinase activity.

Conclusions:

  • Vanadate administration effectively reverses hyperglycemia in streptozotocin-induced diabetic rats.
  • The insulin receptor is a key target mediating the insulin-mimetic effects of vanadate.
  • Vanadate enhances insulin receptor signaling, suggesting therapeutic potential for diabetes management.

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