Insulin degradation. XVIII. On the regulation of glutathione-insulin transhydrogenase in the hyperglycemic obese (ob/ob) mouse.

Abstract

The occurrence of insulin-degrading activity in the liver of the obese hyperglycemic mouse (ob/ob) and its litter mate has been studied. The trichloroacetic acid-soluble product formed from insulin upon incubation with liver homogenate was identified as the A chain of insulin. In Ouchterlony double-diffusion experiments with antibody to purified rat liver glutathione-insulin transhydrogenase, mouse liver homogenate and the microsomal fraction each gave a single precipitation band of identity with the purified rat liver enzyme. These results indicate that the insulin-degrading activity present in the mouse liver is, in fact, glutathione-insulin transhydrogenase. Subcellular distribution studies of glutathione-insulin transhydrogenase and marker enzymes indicate that the transhydrogenase is located primarily in the microsomal fraction of mouse liver homogenate. The ob/ob mouse, which is a genetic mutant characterized by obesity, hyperinsulinism and resistance to the hypoglycemic action of insulin, contains hepatic glutathione-insulin transhydrogenase activity (per mg microsomal protein) markedly higher (40--60%) than its lean litter mates. However, a major portion of the increased hepatic enzyme in the ob/ob mouse occurs in a latent state; the increased amount of enzyme either is unavailable or is nonfunctional, although the ob/ob mouse still contains more of the functional form than the lean mouse. Thus, the results are consistent with the suggestion that the hepatic glutathione-insulin transhydrogenase is probably under a feedback control by circulating insulin.

• Authors: P T Varandani, M A Nafz
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 451 Issue 2 Pg. 382-92 (Dec 21 1976) ISSN: 0006-3002 [Print] Netherlands
• PMID: 187226 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Insulin
• Polyethylene Glycols
• Oxidoreductases
• Succinate Dehydrogenase
• Protein Disulfide Reductase (Glutathione)
• Glucose-6-Phosphatase

Topics

• Animals
• Glucose-6-Phosphatase (metabolism)
• Hyperglycemia (metabolism)
• Immunodiffusion
• Insulin (metabolism)
• Kidney (enzymology)
• Kinetics
• Liver (enzymology)
• Male
• Mice
• Mice, Obese
• Microsomes, Liver (enzymology)
• Muscles (enzymology)
• Myocardium (enzymology)
• Oxidoreductases (metabolism)
• Polyethylene Glycols (pharmacology)
• Protein Disulfide Reductase (Glutathione) (immunology, metabolism)
• Species Specificity
• Subcellular Fractions (enzymology)
• Succinate Dehydrogenase (metabolism)