TY - JOUR
T1 - Fatty acid translocase (FAT/CD36) is localized on insulin-containing granules in human pancreatic β-cells and mediates fatty acid effects on insulin secretion
AU - Noushmehr, Houtan
AU - D'Amico, Eugenio
AU - Farilla, Loredana
AU - Hui, Hongxiang
AU - Wawrowsky, Kolja A.
AU - Mlynarski, Wojciech
AU - Doria, Alessandro
AU - Abumrad, Nada A.
AU - Perfetti, Riccardo
PY - 2005/2
Y1 - 2005/2
N2 - The membrane receptor FAT/CD30 facilitates the major fraction of long-chain fatty acid (FA) uptake by muscle and adipose tissues. In line with the well-known effects of FA metabolism on carbohydrate utilization and insulin responsiveness, altered expression of CB36 has been linked to phenotypic features of the metabolic syndrome including insulin resistance and dyslipidemia. FA metabolism is also known to significantly affect insulin secretion. However, the role of CD36 in this process remains unknown, since its expression levels and function in the pancreas have not been explored. In the present study, freshly isolated human islets and a mouse-derived β-cell line (MIN6) were shown positive for CD36 expression by RT-PCR, Western blot, and immunofluorescence. The identity of flue PCS product was confirmed by microsequencing. The identified transcript was translated and the protein was expressed and subjected to the known posttranslational glycosylation. Fluorescence resonance energy transfer analysis and subcelular protein fractionation indicated that insulin and CD36 are colocalized in the secretory granules of β-cells. Islet CD36 functioned in FA uptake because tins process was blocked by the irreversible CB30 inhibitor sulfosuccinimidyl-oleate. More importantly, sulfosuccinimidyl-oleate reversed enhancing and inhibiting effects, respectively, of acute and long-term palmitate incubations on glucose-dependent insulin secretion. In conclusion, our study demonstrates that human islets express CD36 in the plasma membrane as wel as in the insulin secretory granules. CD36 activity appears important for uptake of FA into β-cells as wel as for mediating their modulatory effects on insulin secretion.
AB - The membrane receptor FAT/CD30 facilitates the major fraction of long-chain fatty acid (FA) uptake by muscle and adipose tissues. In line with the well-known effects of FA metabolism on carbohydrate utilization and insulin responsiveness, altered expression of CB36 has been linked to phenotypic features of the metabolic syndrome including insulin resistance and dyslipidemia. FA metabolism is also known to significantly affect insulin secretion. However, the role of CD36 in this process remains unknown, since its expression levels and function in the pancreas have not been explored. In the present study, freshly isolated human islets and a mouse-derived β-cell line (MIN6) were shown positive for CD36 expression by RT-PCR, Western blot, and immunofluorescence. The identity of flue PCS product was confirmed by microsequencing. The identified transcript was translated and the protein was expressed and subjected to the known posttranslational glycosylation. Fluorescence resonance energy transfer analysis and subcelular protein fractionation indicated that insulin and CD36 are colocalized in the secretory granules of β-cells. Islet CD36 functioned in FA uptake because tins process was blocked by the irreversible CB30 inhibitor sulfosuccinimidyl-oleate. More importantly, sulfosuccinimidyl-oleate reversed enhancing and inhibiting effects, respectively, of acute and long-term palmitate incubations on glucose-dependent insulin secretion. In conclusion, our study demonstrates that human islets express CD36 in the plasma membrane as wel as in the insulin secretory granules. CD36 activity appears important for uptake of FA into β-cells as wel as for mediating their modulatory effects on insulin secretion.
UR - http://www.scopus.com/inward/record.url?scp=12744274513&partnerID=8YFLogxK
U2 - 10.2337/diabetes.54.2.472
DO - 10.2337/diabetes.54.2.472
M3 - Article
C2 - 15677505
AN - SCOPUS:12744274513
SN - 0012-1797
VL - 54
SP - 472
EP - 481
JO - Diabetes
JF - Diabetes
IS - 2
ER -