Early-life programming of susceptibility to dysregulation of glucose metabolism and the development of Type 2 diabetes mellitus

There is increasing epidemiological evidence in humans which associates low birthweight with later metabolic disorders, including insulin resistance and glucose intolerance. There is evidence that nutritional and hormonal factors (e.g. maternal protein restriction, exposure to excess maternal glucoc...

Full description

Saved in:
Bibliographic Details
Published in:Biochemical journal 2000-08, Vol.349 Pt 3 (3), p.657-665
Main Authors: Holness, M J, Langdown, M L, Sugden, M C
Format: Article
Language:English
Subjects:
Adult
Animals
Diabetes Mellitus, Type 2 - epidemiology
Diabetes Mellitus, Type 2 - etiology
Diabetes Mellitus, Type 2 - metabolism
Diabetes Mellitus, Type 2 - physiopathology
Embryonic and Fetal Development
Female
Glucose - metabolism
Humans
Insulin - physiology
Islets of Langerhans
Male
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:There is increasing epidemiological evidence in humans which associates low birthweight with later metabolic disorders, including insulin resistance and glucose intolerance. There is evidence that nutritional and hormonal factors (e.g. maternal protein restriction, exposure to excess maternal glucocorticoids) markedly influence intra-uterine growth and development. A picture is also emerging of the biochemical and physiological mechanisms that may underlie these effects. This review focuses on recent research directed towards understanding the molecular basis of the relationship between indices of poor early growth and the subsequent development of glucose intolerance and Type 2 diabetes mellitus using animal models that attempt to recreate the process of programming via an adverse intra-uterine or neonatal environment. Emphasis is on the chain of events and potential mechanisms by which adverse adaptations affect pancreatic-beta-cell insulin secretion and the sensitivity to insulin of key metabolic processes, including hepatic glucose production, skeletal-muscle glucose disposal and adipose-tissue lipolysis. Unravelling the molecular details involved in metabolic programming may provide new insights into the pathogenesis of impaired glucoregulation and Type 2 diabetes.
ISSN:0264-6021
1470-8728
DOI:10.1042/bj3490657