Antidiabetic properties of zinc-alpha2-glycoprotein in ob/ob mice

Endocrinology. 2010 Mar;151(3):948-57. doi: 10.1210/en.2009-0827. Epub 2009 Dec 23.

Abstract

Zinc-alpha(2)-glycoprotein (ZAG) is an adipokine associated with fat loss in cancer cachexia. The purpose of this study was to evaluate the ability of recombinant human ZAG to attenuate type 2 diabetes in the ob/ob mouse model. ZAG (50 microg daily, iv) induced a progressive loss of body weight (3.5 g in 5 d), without an effect on food or water intake but with a 0.4 C rise in body temperature, suggesting an increased energy expenditure. Despite an increased plasma glycerol, indicative of increased lipolysis, levels of glucose, triglycerides, and nonesterified fatty acids were decreased by 17, 25, and 62%, respectively, due to an increased use of both glucose and lipids by muscle and brown adipose tissue. The weight of the latter increased 2-fold, and there was increased expression of uncoupling proteins-1 and -3. Plasma insulin levels were reduced by 36%, whereas pancreatic insulin was increased 4-fold, and there was a 53% decrease in the total area under the glucose curve in the glucose tolerance test and reduced insulin requirement. There was an increase in skeletal muscle mass due to an increase in protein synthesis and a decrease in protein degradation. These results suggest that ZAG may potentially be effective in the treatment of type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / therapeutic use*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Disease Models, Animal
  • Glucose / metabolism
  • Glycoproteins / therapeutic use*
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / blood
  • Insulin Resistance
  • Male
  • Mice
  • Recombinant Proteins / therapeutic use

Substances

  • AZGP1 protein, human
  • Carrier Proteins
  • Glycoproteins
  • Hypoglycemic Agents
  • Insulin
  • Recombinant Proteins
  • Glucose