In vivo chloroquine-induced inhibition of insulin degradation in a diabetic patient with severe insulin resistance.

Abstract:

:We report on a 26-yr-old patient with an 11-yr history of insulin-dependent diabetes mellitus who exhibited insulin resistance with a requirement of up to 15,000 U of intravenous (i.v.) insulin/day. Attempts to diminish her insulin requirement by administration of sulfated insulin or Trasylol were unsuccessful, with the patient remaining resistant to subcutaneous (s.c.) and i.v. administration of pure pork insulin. Chloroquine phosphate therapy (500 mg twice a day) resulted in a decreased requirement for i.v. insulin (700 U/day as compared with the pretreatment requirement of 8400 U/day). Accelerated insulin degradation in s.c. fat tissue of the patient before treatment with chloroquine was demonstrated. This activity was decreased by 64% during chloroquine therapy. Inhibition of insulin degrading activity (IDA) during chloroquine therapy was associated with reductions in the leukocyte lysosomal enzymes alpha-galactosidase and hexosaminidase-A but not hexosaminidase-B and beta-glucuronidase. This study constitutes the first reported use of chloroquine for treatment of insulin resistance as a result of accelerated insulin degradation, and it provides evidence of the effectiveness of this agent in this rare condition.

journal_name

Diabetes

journal_title

Diabetes

authors

Blazar BR,Whitley CB,Kitabchi AE,Tsai MY,Santiago J,White N,Stentz FB,Brown DM

doi

10.2337/diab.33.12.1133

subject

Has Abstract

pub_date

1984-12-01 00:00:00

pages

1133-7

issue

12

eissn

0012-1797

issn

1939-327X

journal_volume

33

pub_type

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