Secretion of glycated insulin from pancreatic beta-cells in diabetes represents a novel aspect of beta-cell dysfunction and glucose toxicity.
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.
McKillop
A M
AM
School of Biomedical Sciences, University of Ulster, Coleraine, N. Ireland, UK BT52 1SA. am.mckillop@ulst.ac.uk
Abdel-Wahab
Y H A
YH
Mooney
M H
MH
O'Harte
F P M
FP
Flatt
P R
PR
D000595:Amino Acid Sequence; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000503:physiopathology*; D006031:Glycosylation; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology; D007328:Insulin / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data
D001786:Blood Glucose; D007328:Insulin; C039522:insulin, glycosylated