GLP-1 and GLP-2 as Yin and Yang of Intestinal Lipoprotein Production
| Autor: | Gustavo J. Hein, Khosrow Adeli, Joanne Hsieh, Christopher Baker, Sarah Farr |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
endocrine system
0303 health sciences medicine.medical_specialty Endocrinology Diabetes and Metabolism digestive oral and skin physiology 030209 endocrinology & metabolism Lipid metabolism Proglucagon Biology Glucagon-like peptide-2 Glucagon-like peptide-1 Intestinal absorption 3. Good health 03 medical and health sciences 0302 clinical medicine Endocrinology Postprandial Internal medicine Internal Medicine medicine hormones hormone substitutes and hormone antagonists 030304 developmental biology Lipoprotein Chylomicron |
| Zdroj: | Diabetes. 62:373-381 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db12-0202 |
| Popis: | The glucagon-like peptides (GLP-1 and GLP-2) are processed from the proglucagon polypeptide and secreted in equimolar amounts but have opposite effects on chylomicron (CM) production, with GLP-1 significantly reducing and GLP-2 increasing postprandial chylomicronemia. In the current study, we evaluated the apparent paradoxical roles of GLP-1 and GLP-2 under physiological conditions in the Syrian golden hamster, a model with close similarity to humans in terms of lipoprotein metabolism. A short (30-min) intravenous infusion of GLP-2 resulted in a marked increase in postprandial apolipoprotein B48 (apoB48) and triglyceride (TG) levels in the TG-rich lipoprotein (TRL) fraction, whereas GLP-1 infusion decreased lipid absorption and levels of TRL-TG and apoB48. GLP-1 and GLP-2 coinfusion resulted in net increased lipid absorption and an increase in TRL-TG and apoB48. However, prolonged (120-min) coinfusion of GLP-1 and GLP-2 decreased postprandial lipemia. Blocking dipeptidyl peptidase-4 activity resulted in decreased postprandial lipemia. Interestingly, fructose-fed, insulin-resistant hamsters showed a more pronounced response, including possible hypersensitivity to GLP-2 or reduced sensitivity to GLP-1. In conclusion, under normal physiological conditions, the actions of GLP-2 predominate; however, when GLP-1 activity is sustained, the hypolipidemic action of GLP-1 predominates. Pharmacological inhibition of GLP-1 degradation tips the balance toward an inhibitory effect on intestinal production of atherogenic CM particles. |
| Databáze: | OpenAIRE |
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