Glycation of insulin in the islets of Langerhans of normal and diabetic animals

Yasser Abdel-Wahab, Finbarr O'Harte, H Ratcliff, Neville McClenaghan, CR Barnett, Peter Flatt

Research output: Contribution to journalArticle

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Abstract

The glycation of immunoreactive insulin (IRI) was assessed in extracts of pancreas and islets from control and hyperglycemic animal models. Glycated and nonglycated IRI were separated by affinity chromatography and quantified by radioimmunoassay. Hydrocortisone-treated Wistar rats (80 mg . kg(-1) . day(-1)) and obese hyperglycemic (ob/ob) mice showed significant increases in plasma glucose (P <0.001), percentage glycated hemoglobin (P <0.001), plasma IRI (P <0.01), and total pancreatic IRI content (P <0.01), compared with their respective controls. These diabetic groups also demonstrated significant increases (P <0.05) in the percentage of glycated pancreatic IRI above the controls. Streptozotocin-treated (200 mg/kg) swiss TO mice exhibited significant increases in plasma glucose (P <0.001), glycated hemoglobin (P <0.001), and percentage glycated pancreatic IRI (P <0.05), compared with untreated controls, despite a marked decrease in both plasma IRI (P <0.001) and total pancreatic IRI content (P <0.001). Significant elevations in the percentage of glycated IRI were also observed in islets isolated from obese hyperglycemic (ob/ob) mice (P <0.001), compared with islets from lean controls, and when lean mouse islets were cultured in hyperglycemic media for 24 h (33.3 vs. 5.6 mmol/l D-glucose; P <0.001). The contribution of glycated plus nonglycated insulin and proinsulin to the total IRI was estimated in lean and obese mouse pancreatic extracts following high-performance liquid chromatography separation. The contribution of proinsulin to the total IRI was approximately 10%. Proinsulin represented 27-28% of the total glycated IRI. These data indicate that the glycation of insulin and proinsulin occurs within the pancreatic islets and is elevated in both insulin-deficient and insulin-resistant diabetic animal models.
LanguageEnglish
Pages1489-1496
JournalDiabetes
Volume45
Issue number11
Publication statusPublished - Nov 1996

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Islets of Langerhans
Insulin
Proinsulin
Glycosylated Hemoglobin A
Glucose
Animal Models
Pancreatic Extracts
Obese Mice
Streptozocin
Affinity Chromatography
Radioimmunoassay
Hydrocortisone
Wistar Rats
Pancreas
High Pressure Liquid Chromatography

Cite this

Abdel-Wahab, Yasser ; O'Harte, Finbarr ; Ratcliff, H ; McClenaghan, Neville ; Barnett, CR ; Flatt, Peter. / Glycation of insulin in the islets of Langerhans of normal and diabetic animals. In: Diabetes. 1996 ; Vol. 45, No. 11. pp. 1489-1496.
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abstract = "The glycation of immunoreactive insulin (IRI) was assessed in extracts of pancreas and islets from control and hyperglycemic animal models. Glycated and nonglycated IRI were separated by affinity chromatography and quantified by radioimmunoassay. Hydrocortisone-treated Wistar rats (80 mg . kg(-1) . day(-1)) and obese hyperglycemic (ob/ob) mice showed significant increases in plasma glucose (P <0.001), percentage glycated hemoglobin (P <0.001), plasma IRI (P <0.01), and total pancreatic IRI content (P <0.01), compared with their respective controls. These diabetic groups also demonstrated significant increases (P <0.05) in the percentage of glycated pancreatic IRI above the controls. Streptozotocin-treated (200 mg/kg) swiss TO mice exhibited significant increases in plasma glucose (P <0.001), glycated hemoglobin (P <0.001), and percentage glycated pancreatic IRI (P <0.05), compared with untreated controls, despite a marked decrease in both plasma IRI (P <0.001) and total pancreatic IRI content (P <0.001). Significant elevations in the percentage of glycated IRI were also observed in islets isolated from obese hyperglycemic (ob/ob) mice (P <0.001), compared with islets from lean controls, and when lean mouse islets were cultured in hyperglycemic media for 24 h (33.3 vs. 5.6 mmol/l D-glucose; P <0.001). The contribution of glycated plus nonglycated insulin and proinsulin to the total IRI was estimated in lean and obese mouse pancreatic extracts following high-performance liquid chromatography separation. The contribution of proinsulin to the total IRI was approximately 10{\%}. Proinsulin represented 27-28{\%} of the total glycated IRI. These data indicate that the glycation of insulin and proinsulin occurs within the pancreatic islets and is elevated in both insulin-deficient and insulin-resistant diabetic animal models.",
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Abdel-Wahab, Y, O'Harte, F, Ratcliff, H, McClenaghan, N, Barnett, CR & Flatt, P 1996, 'Glycation of insulin in the islets of Langerhans of normal and diabetic animals', Diabetes, vol. 45, no. 11, pp. 1489-1496.

Glycation of insulin in the islets of Langerhans of normal and diabetic animals. / Abdel-Wahab, Yasser; O'Harte, Finbarr; Ratcliff, H; McClenaghan, Neville; Barnett, CR; Flatt, Peter.

In: Diabetes, Vol. 45, No. 11, 11.1996, p. 1489-1496.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Glycation of insulin in the islets of Langerhans of normal and diabetic animals

AU - Abdel-Wahab, Yasser

AU - O'Harte, Finbarr

AU - Ratcliff, H

AU - McClenaghan, Neville

AU - Barnett, CR

AU - Flatt, Peter

PY - 1996/11

Y1 - 1996/11

N2 - The glycation of immunoreactive insulin (IRI) was assessed in extracts of pancreas and islets from control and hyperglycemic animal models. Glycated and nonglycated IRI were separated by affinity chromatography and quantified by radioimmunoassay. Hydrocortisone-treated Wistar rats (80 mg . kg(-1) . day(-1)) and obese hyperglycemic (ob/ob) mice showed significant increases in plasma glucose (P <0.001), percentage glycated hemoglobin (P <0.001), plasma IRI (P <0.01), and total pancreatic IRI content (P <0.01), compared with their respective controls. These diabetic groups also demonstrated significant increases (P <0.05) in the percentage of glycated pancreatic IRI above the controls. Streptozotocin-treated (200 mg/kg) swiss TO mice exhibited significant increases in plasma glucose (P <0.001), glycated hemoglobin (P <0.001), and percentage glycated pancreatic IRI (P <0.05), compared with untreated controls, despite a marked decrease in both plasma IRI (P <0.001) and total pancreatic IRI content (P <0.001). Significant elevations in the percentage of glycated IRI were also observed in islets isolated from obese hyperglycemic (ob/ob) mice (P <0.001), compared with islets from lean controls, and when lean mouse islets were cultured in hyperglycemic media for 24 h (33.3 vs. 5.6 mmol/l D-glucose; P <0.001). The contribution of glycated plus nonglycated insulin and proinsulin to the total IRI was estimated in lean and obese mouse pancreatic extracts following high-performance liquid chromatography separation. The contribution of proinsulin to the total IRI was approximately 10%. Proinsulin represented 27-28% of the total glycated IRI. These data indicate that the glycation of insulin and proinsulin occurs within the pancreatic islets and is elevated in both insulin-deficient and insulin-resistant diabetic animal models.

AB - The glycation of immunoreactive insulin (IRI) was assessed in extracts of pancreas and islets from control and hyperglycemic animal models. Glycated and nonglycated IRI were separated by affinity chromatography and quantified by radioimmunoassay. Hydrocortisone-treated Wistar rats (80 mg . kg(-1) . day(-1)) and obese hyperglycemic (ob/ob) mice showed significant increases in plasma glucose (P <0.001), percentage glycated hemoglobin (P <0.001), plasma IRI (P <0.01), and total pancreatic IRI content (P <0.01), compared with their respective controls. These diabetic groups also demonstrated significant increases (P <0.05) in the percentage of glycated pancreatic IRI above the controls. Streptozotocin-treated (200 mg/kg) swiss TO mice exhibited significant increases in plasma glucose (P <0.001), glycated hemoglobin (P <0.001), and percentage glycated pancreatic IRI (P <0.05), compared with untreated controls, despite a marked decrease in both plasma IRI (P <0.001) and total pancreatic IRI content (P <0.001). Significant elevations in the percentage of glycated IRI were also observed in islets isolated from obese hyperglycemic (ob/ob) mice (P <0.001), compared with islets from lean controls, and when lean mouse islets were cultured in hyperglycemic media for 24 h (33.3 vs. 5.6 mmol/l D-glucose; P <0.001). The contribution of glycated plus nonglycated insulin and proinsulin to the total IRI was estimated in lean and obese mouse pancreatic extracts following high-performance liquid chromatography separation. The contribution of proinsulin to the total IRI was approximately 10%. Proinsulin represented 27-28% of the total glycated IRI. These data indicate that the glycation of insulin and proinsulin occurs within the pancreatic islets and is elevated in both insulin-deficient and insulin-resistant diabetic animal models.

M3 - Article

VL - 45

SP - 1489

EP - 1496

JO - Diabetes

T2 - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 11

ER -