Glycation of insulin results in reduced biological activity in mice.

Abstract:

:Bovine insulin was glycated by in vitro incubation with 20-220 mM D-glucose for 1-48 h. The percentage of glycation was dependent on time, glucose concentration, temperature and pH, attaining values up to 28%. Glucose-lowering activities of glycated and control (non-glycated) insulin preparations were assessed in mice by intraperitoneal injection in a 39% (w/v) glucose solution (2 g/kg body weight) at doses of 0.05 and 0.25 units/kg body weight. Injection of glucose alone significantly (P < 0.001) increased plasma glucose concentrations at 30 min. Simultaneous administration of non-glycated insulin with glucose significantly decreased the 30-min glycaemic excursion (P < 0.001) in a dose-dependent manner. Glycated insulin exhibited a significant reduction (P < 0.001) in glucose-lowering activity under these conditions. The relationship between the extent of insulin glycation and glucose-lowering activity at 0.25 units/kg was assessed using five different insulin preparations glycated between 6%-28%. The insulin-induced decrease in plasma glucose at 30 min was inversely related to the extent of glycation (r = 0.99). Glycated insulin (10(-8) and 10(-6) M) also exhibited a significantly reduced (P < 0.05) ability to stimulate glucose oxidation in isolated mouse diaphragm muscle compared with non-glycated insulin. These data indicate that glycated insulin exhibits impaired biological activity which may contribute to glucose intolerance in diabetes. Further studies are required to determine if glycation of insulin occurs in man and if this process contributes to the pathogenesis of diabetes.

journal_name

Acta Diabetol

journal_title

Acta diabetologica

authors

Abdel-Wahab YH,O'Harte FP,Boyd AC,Barnett CR,Flatt PR

doi

10.1007/s005920050086

subject

Has Abstract

pub_date

1997-12-01 00:00:00

pages

265-70

issue

4

eissn

0940-5429

issn

1432-5233

journal_volume

34

pub_type

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