Glycation of insulin results in reduced biological activity in mice

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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 (nonglycated) 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.
LanguageEnglish
Pages265-270
JournalActa Diabetologica
Volume34
Issue number4
Publication statusPublished - 1997

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Insulin
Glucose
Body Weight
Glucose Intolerance
Diaphragm
Intraperitoneal Injections
glycosylated insulin
Muscles
Injections
Temperature

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title = "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 (nonglycated) 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.",
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Glycation of insulin results in reduced biological activity in mice. / Abdel-Wahab, Yasser; O'Harte, Finbarr; Boyd, AC; Barnett, CR; Flatt, Peter.

In: Acta Diabetologica, Vol. 34, No. 4, 1997, p. 265-270.

Research output: Contribution to journalArticle

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T1 - Glycation of insulin results in reduced biological activity in mice

AU - Abdel-Wahab, Yasser

AU - O'Harte, Finbarr

AU - Boyd, AC

AU - Barnett, CR

AU - Flatt, Peter

PY - 1997

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N2 - 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 (nonglycated) 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.

AB - 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 (nonglycated) 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.

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