Document Detail


Glucose-dependent Insulinotropic Polypeptide (GIP): From prohormone to actions in endocrine pancreas and adipose tissue.
MedLine Citation:
PMID:  22142579     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
The present thesis consists of one published article and one draft manuscript. Interest in the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) was reignited by the discovery that GIP receptor deficient mice were unable to gain weight in response to high fat feeding. However, the path from processing of the prohormone to regulation of secretion and establishment of its role in the complicated network of mediators involved in energy mobilization is not fully understood. The biologically active GIP1-42 was found in vivo to be dependent on processing from the immature prohormone by proprotein convertase 1/3 (PC1/3) in the intestinal K-cell. Even so, ~50% of GIP immunoreactive cells do not express PC1/3 raising the possibility that subsets of K-cells exist in which the precursor may be cleaved at alternative sites. Cell line studies did demonstrate that another convertase in endocrine cell types, PC2, mediated cleavage at alternative sites liberating larger and smaller GIP fragments. It was possible to detect fragments of similar size in gel filtration extracts of murine upper jejunum, but the identity, mechanism of processing and function of these immunoreactivities remains uncertain. Once correctly processed GIP1-42 is secreted in response to food intake. The K-cell is believed to directly sense and respond to nutrients in the intestine, but as the molecular profiling of this cell type has just begun, the nutrient sensing machinery and possible feedback regulation are still poorly characterized. When secreted to the blood stream, GIP acts as a mediator of energy mobilization in a complex network with other hormones. An acute and established function of GIP is to exert its incretin function thereby enhancing glucose stimulated insulin secretion necessary for prompt disposal of nutrients, yet GIP also stimulates glucagon secretion to increase blood glucose. In the diabetic state the insulinotropic effect of GIP is impaired and an early inexpedient glucagon stimulation in response to a meal further counteracts effects of insulin and worsens glycaemic control. A demonstration that GIP receptor deficient mice were resistant to diet induced obesity let to the categorization of GIP as a fat promoting hormone and direct insulin-mimetic effects in adipose tissue has been proposed. We were able to demonstrate a redundancy for the GIP receptor in incorporation of lipids into adipocytes. We also observed that GIP receptor deficient mice could respond normally to high fat feeding with increased fat mass, but failed to increase lean mass. Mice with rescue of the GIP receptor in adipose tissue normalized the body composition in response to high fat diet, but the mice had a lower total body weight. In contrast, the GIP receptor expressed in the pancreatic beta-cell was able to promote lean mass gain on a low fat diet, but not on a high fat diet. Overall, we have established principal requirements for GIP maturation. Furthermore, we have demonstrated that neither beta-cell nor adipocyte GIP receptor expression can replace the endogenous GIP receptor in regulation of body weight and body composition.
Authors:
Randi Ugleholdt
Related Documents :
8880419 - Breed differences in boar taint: relationship between tissue levels boar taint compound...
15729899 - Utilization of ensiled sweet potato (ipomoea batatas (l.) lam.) leaves as a protein sup...
11063299 - Feeder location did not affect performance of weanling pigs in large groups.
12413089 - Low-phytic acid barley improves calcium and phosphorus utilization and growth performan...
3598719 - Isoleucine requirement of young growing male guinea pigs.
7730179 - The effects of spray-dried blood meal on growth performance of the early-weaned pig.
12075589 - Igf2 genotype and obesity in men and women across the adult age span.
17969379 - Apolipoproteins a-i and b: biosynthesis, role in the development of atherosclerosis and...
8858459 - Anti-toxoplasma effect of pyrimethamine, trimethoprim and sulphonamides alone and in co...
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Danish medical bulletin     Volume:  58     ISSN:  1603-9629     ISO Abbreviation:  Dan Med Bull     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-06     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0066040     Medline TA:  Dan Med Bull     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  B4368     Citation Subset:  IM    
Affiliation:
Department of Biomedical Sciences, Cellular and Metabolic Research Section, University of Copenhagen, Faculty of Health Sciences, Blegdamsvej 3B build. 12.2, 2200 Copenhagen N, Denmark. randi@ugleholdt.com.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Birth outcome in women with ulcerative colitis and Crohn's disease, and pharmacoepidemiological aspe...
Next Document:  Pain and convalescence following laparoscopic ven-tral hernia repair.