Journal article
Adipose differentiation-related protein regulates lipids and insulin in pancreatic islets
American journal of physiology: endocrinology and metabolism, Vol.299(2), pp.E249-E257
08/2010
DOI: 10.1152/ajpendo.00646.2009
PMCID: PMC2928510
PMID: 20484013
Abstract
The excess accumulation of lipids in islets is thought to contribute to the development of diabetes in obesity by impairing β-cell function. However, lipids also serve a nutrient function in islets, and fatty acids acutely increase insulin secretion. A better understanding of lipid metabolism in islets will shed light on complex effects of lipids on β-cells. Adipose differentiation-related protein (ADFP) is localized on the surface of lipid droplets in a wide range of cells and plays an important role in intracellular lipid metabolism. We found that ADFP was highly expressed in murine β-cells. Moreover, islet ADFP was increased in mice on a high-fat diet (3.5-fold of control) and after fasting (2.5-fold of control), revealing dynamic changes in ADFP in response to metabolic cues. ADFP expression was also increased by addition of fatty acids in human islets. The downregulation of ADFP in MIN6 cells by antisense oligonucleotide (ASO) suppressed the accumulation of triglycerides upon fatty acid loading (56% of control) along with a reduction in the mRNA levels of lipogenic genes such as diacylglycerol
O
-acyltransferase-2 and fatty acid synthase. Fatty acid uptake, oxidation, and lipolysis were also reduced by downregulation of ADFP. Moreover, the reduction of ADFP impaired the ability of palmitate to increase insulin secretion. These findings demonstrate that ADFP is important in regulation of lipid metabolism and insulin secretion in β-cells.
Details
- Title: Subtitle
- Adipose differentiation-related protein regulates lipids and insulin in pancreatic islets
- Creators
- D. M Faleck - Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PennsylvaniaK Ali - Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PennsylvaniaR Roat - Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PennsylvaniaM. J Graham - Isis Pharmaceuticals, Carlsbad, California; andR. M Crooke - Isis Pharmaceuticals, Carlsbad, California; andR Battisti - Department of Internal Medicine, Strelitz Diabetes Center, Eastern Virginia Medical School, Norfolk, VirginiaE Garcia - Department of Internal Medicine, Strelitz Diabetes Center, Eastern Virginia Medical School, Norfolk, VirginiaR. S Ahima - Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PennsylvaniaY Imai - Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
- Resource Type
- Journal article
- Publication Details
- American journal of physiology: endocrinology and metabolism, Vol.299(2), pp.E249-E257
- DOI
- 10.1152/ajpendo.00646.2009
- PMID
- 20484013
- PMCID
- PMC2928510
- NLM abbreviation
- Am J Physiol Endocrinol Metab
- ISSN
- 0193-1849
- eISSN
- 1522-1555
- Publisher
- American Physiological Society
- Language
- English
- Date published
- 08/2010
- Academic Unit
- Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984094746002771
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