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Alpha cell function in health and disease: influence of glucagon-like peptide-1

Dunning, B E; Foley, J E and Ahrén, Bo LU (2005) In Diabetologia 48(9). p.1700-1713
Abstract
Although there is abundant evidence that hyperglucagonaemia plays a key role in the development of hyperglycaemia in type 2 diabetes, efforts to understand and correct this abnormality have been overshadowed by the emphasis on insulin secretion and action. However, recognition that the incretin hormone glucagon-like peptide-1 (GLP-1) exerts opposing effects on glucagon and insulin secretion has revived interest in glucagon, the neglected partner of insulin, in the bihormonal hypothesis. In healthy subjects, glucagon secretion is regulated by a variety of nutrient, neural and hormonal factors, the most important of which is glucose. The defect in alpha cell function that occurs in type 2 diabetes reflects impaired glucose sensing. GLP-1... (More)
Although there is abundant evidence that hyperglucagonaemia plays a key role in the development of hyperglycaemia in type 2 diabetes, efforts to understand and correct this abnormality have been overshadowed by the emphasis on insulin secretion and action. However, recognition that the incretin hormone glucagon-like peptide-1 (GLP-1) exerts opposing effects on glucagon and insulin secretion has revived interest in glucagon, the neglected partner of insulin, in the bihormonal hypothesis. In healthy subjects, glucagon secretion is regulated by a variety of nutrient, neural and hormonal factors, the most important of which is glucose. The defect in alpha cell function that occurs in type 2 diabetes reflects impaired glucose sensing. GLP-1 inhibits glucagon secretion in vitro and in vivo in experimental animals, and suppresses glucagon release in a glucose-dependent manner in healthy subjects. This effect is also evident in diabetic patients, but GLP-1 does not inhibit glucagon release in response to hypoglycaemia, and may even enhance it. Early clinical studies with agents acting through GLP-1 signalling mechanisms (e.g. exenatide, liraglutide and vildagliptin) suggest that GLP-1 can improve alpha cell glucose sensing in patients with type 2 diabetes. Therapeutic approaches based around GLP-1 have the potential to improve both alpha cell and beta cell function, and could be of benefit in patients with a broad range of metabolic disorders. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
IGT, dipeptidyl peptidase IV, diabetes treatment, DPP-4, GLP-1, glucagon-like peptide-1, glucagon, incretin, impaired glucose tolerance
in
Diabetologia
volume
48
issue
9
pages
1700 - 1713
publisher
Springer Verlag
external identifiers
  • wos:000231939300003
  • pmid:16132964
  • scopus:24944577486
ISSN
1432-0428
DOI
10.1007/s00125-005-1878-0
language
English
LU publication?
yes
id
9041f109-2a1f-48c3-92d6-44fbbbbe2fea (old id 224545)
date added to LUP
2007-08-02 15:29:23
date last changed
2017-11-05 03:28:55
@article{9041f109-2a1f-48c3-92d6-44fbbbbe2fea,
  abstract     = {Although there is abundant evidence that hyperglucagonaemia plays a key role in the development of hyperglycaemia in type 2 diabetes, efforts to understand and correct this abnormality have been overshadowed by the emphasis on insulin secretion and action. However, recognition that the incretin hormone glucagon-like peptide-1 (GLP-1) exerts opposing effects on glucagon and insulin secretion has revived interest in glucagon, the neglected partner of insulin, in the bihormonal hypothesis. In healthy subjects, glucagon secretion is regulated by a variety of nutrient, neural and hormonal factors, the most important of which is glucose. The defect in alpha cell function that occurs in type 2 diabetes reflects impaired glucose sensing. GLP-1 inhibits glucagon secretion in vitro and in vivo in experimental animals, and suppresses glucagon release in a glucose-dependent manner in healthy subjects. This effect is also evident in diabetic patients, but GLP-1 does not inhibit glucagon release in response to hypoglycaemia, and may even enhance it. Early clinical studies with agents acting through GLP-1 signalling mechanisms (e.g. exenatide, liraglutide and vildagliptin) suggest that GLP-1 can improve alpha cell glucose sensing in patients with type 2 diabetes. Therapeutic approaches based around GLP-1 have the potential to improve both alpha cell and beta cell function, and could be of benefit in patients with a broad range of metabolic disorders.},
  author       = {Dunning, B E and Foley, J E and Ahrén, Bo},
  issn         = {1432-0428},
  keyword      = {IGT,dipeptidyl peptidase IV,diabetes treatment,DPP-4,GLP-1,glucagon-like peptide-1,glucagon,incretin,impaired glucose tolerance},
  language     = {eng},
  number       = {9},
  pages        = {1700--1713},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {Alpha cell function in health and disease: influence of glucagon-like peptide-1},
  url          = {http://dx.doi.org/10.1007/s00125-005-1878-0},
  volume       = {48},
  year         = {2005},
}