Secretion of glycated insulin from pancreatic beta-cells in diabetes represents a novel aspect of beta-cell dysfunction and glucose toxicity

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Abstract

Hyperglycaemia, a significant pathophysiological state in diabetes mellitus, may contribute to defective pancreatic beta-cell function, secretion and action of insulin through glycation of important regulatory proteins. This paper highlights recent data supporting the concept that pancreatic beta-cell dysfunction is associated with increased glycation of functional proteins. The pancreatic beta-cell provides a highly favourable environment for the intracellular glycation of insulin which is a relatively rapid, glucose-dependent process. Using a novel radioimmunoassay and immunocytochemical techniques, glycated insulin has been shown to be stored and secreted from pancreatic beta-cells in both human and animal models of diabetes. Glycated insulin represents a significant proportion of total circulating insulin in type 2 diabetes and may have impaired metabolic clearance compared with native insulin. Since glycation of insulin disturbs normal cellular function and results in decreased biological activity, it may play a significant contributory role in the insulin resistance and glucose intolerance of type 2 diabetes. Further studies are necessary to evaluate the possible significance of glycated insulin in both the pathophysiology of diabetes and future therapeutic approaches.
LanguageEnglish
PagesS61-S69
JournalDiabetes and Metabolism
Volume28
Issue number6, Par
Publication statusPublished - Dec 2002

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Insulin-Secreting Cells
Insulin
Glucose
Type 2 Diabetes Mellitus
Glucose Intolerance
Hyperglycemia
Radioimmunoassay
Insulin Resistance
Diabetes Mellitus
Proteins
Animal Models
glycosylated insulin

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title = "Secretion of glycated insulin from pancreatic beta-cells in diabetes represents a novel aspect of beta-cell dysfunction and glucose toxicity",
abstract = "Hyperglycaemia, a significant pathophysiological state in diabetes mellitus, may contribute to defective pancreatic beta-cell function, secretion and action of insulin through glycation of important regulatory proteins. This paper highlights recent data supporting the concept that pancreatic beta-cell dysfunction is associated with increased glycation of functional proteins. The pancreatic beta-cell provides a highly favourable environment for the intracellular glycation of insulin which is a relatively rapid, glucose-dependent process. Using a novel radioimmunoassay and immunocytochemical techniques, glycated insulin has been shown to be stored and secreted from pancreatic beta-cells in both human and animal models of diabetes. Glycated insulin represents a significant proportion of total circulating insulin in type 2 diabetes and may have impaired metabolic clearance compared with native insulin. Since glycation of insulin disturbs normal cellular function and results in decreased biological activity, it may play a significant contributory role in the insulin resistance and glucose intolerance of type 2 diabetes. Further studies are necessary to evaluate the possible significance of glycated insulin in both the pathophysiology of diabetes and future therapeutic approaches.",
author = "Aine McKillop and Yasser Abdel-Wahab and MH Mooney and Finbarr O'Harte and Peter Flatt",
note = "Workshop on the Endocrine Pancreas, BRUSSELS, BELGIUM, DEC 08, 2001",
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journal = "Diabetes and Metabolism",
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T1 - Secretion of glycated insulin from pancreatic beta-cells in diabetes represents a novel aspect of beta-cell dysfunction and glucose toxicity

AU - McKillop, Aine

AU - Abdel-Wahab, Yasser

AU - Mooney, MH

AU - O'Harte, Finbarr

AU - Flatt, Peter

N1 - Workshop on the Endocrine Pancreas, BRUSSELS, BELGIUM, DEC 08, 2001

PY - 2002/12

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N2 - Hyperglycaemia, a significant pathophysiological state in diabetes mellitus, may contribute to defective pancreatic beta-cell function, secretion and action of insulin through glycation of important regulatory proteins. This paper highlights recent data supporting the concept that pancreatic beta-cell dysfunction is associated with increased glycation of functional proteins. The pancreatic beta-cell provides a highly favourable environment for the intracellular glycation of insulin which is a relatively rapid, glucose-dependent process. Using a novel radioimmunoassay and immunocytochemical techniques, glycated insulin has been shown to be stored and secreted from pancreatic beta-cells in both human and animal models of diabetes. Glycated insulin represents a significant proportion of total circulating insulin in type 2 diabetes and may have impaired metabolic clearance compared with native insulin. Since glycation of insulin disturbs normal cellular function and results in decreased biological activity, it may play a significant contributory role in the insulin resistance and glucose intolerance of type 2 diabetes. Further studies are necessary to evaluate the possible significance of glycated insulin in both the pathophysiology of diabetes and future therapeutic approaches.

AB - Hyperglycaemia, a significant pathophysiological state in diabetes mellitus, may contribute to defective pancreatic beta-cell function, secretion and action of insulin through glycation of important regulatory proteins. This paper highlights recent data supporting the concept that pancreatic beta-cell dysfunction is associated with increased glycation of functional proteins. The pancreatic beta-cell provides a highly favourable environment for the intracellular glycation of insulin which is a relatively rapid, glucose-dependent process. Using a novel radioimmunoassay and immunocytochemical techniques, glycated insulin has been shown to be stored and secreted from pancreatic beta-cells in both human and animal models of diabetes. Glycated insulin represents a significant proportion of total circulating insulin in type 2 diabetes and may have impaired metabolic clearance compared with native insulin. Since glycation of insulin disturbs normal cellular function and results in decreased biological activity, it may play a significant contributory role in the insulin resistance and glucose intolerance of type 2 diabetes. Further studies are necessary to evaluate the possible significance of glycated insulin in both the pathophysiology of diabetes and future therapeutic approaches.

M3 - Article

VL - 28

SP - S61-S69

JO - Diabetes and Metabolism

T2 - Diabetes and Metabolism

JF - Diabetes and Metabolism

SN - 1262-3636

IS - 6, Par

ER -