التفاصيل البيبلوغرافية
| العنوان: |
Altered insulin secretion associated with reduced lipolytic efficiency in aP2-/- mice. |
| المؤلفون: |
Scheja, Ludger, Makowski, Liza, Uysal, K. Teoman, Wiesbrock, Sarah M., Shimshek, Derya R., Meyers, Daniel S., Morgan, Maureen, Parker, Rex A., Hotamisligil, Gokhan S., Scheja, L, Makowski, L, Uysal, K T, Wiesbrock, S M, Shimshek, D R, Meyers, D S, Morgan, M, Parker, R A, Hotamisligil, G S |
| المصدر: |
Diabetes; Oct99, Vol. 48 Issue 10, p1987-1994, 8p, 1 Black and White Photograph, 1 Chart, 6 Graphs |
| مصطلحات موضوعية: |
FATTY acid-binding proteins, PROTEIN deficiency, LIPOLYSIS, INSULIN, SECRETION, PROTEIN metabolism, ADIPOSE tissues, ANIMAL experimentation, BETA adrenoceptors, CARRIER proteins, CELL culture, CELL receptors, COMPARATIVE studies, FAT cells, FATTY acids, GENES, GENETIC disorders, LIPID metabolism disorders, RESEARCH methodology, MEDICAL cooperation, MICE, NERVE tissue proteins, PROTEINS, RESEARCH, RESEARCH funding, EVALUATION research |
| مستخلص: |
Recent studies have shown that genetic deficiency of the adipocyte fatty acid-binding protein (aP2) results in minor alterations of plasma lipids and adipocyte development but provides significant protection from dietary obesity-induced hyperinsulinemia and insulin resistance. To identify potential mechanisms responsible for this phenotype, we examined lipolysis and insulin secretion in aP2-/- mice. Beta-adrenergic stimulation resulted in a blunted rise of blood glycerol levels in aP2-/- compared with aP2+/+ mice, suggesting diminished lipolysis in aP2-/- adipocytes. Confirming this, primary adipocytes isolated from aP2-/- mice showed attenuated glycerol and free fatty acid (FFA) release in response to dibutyryl cAMP. The decreased lipolytic response seen in the aP2-/- mice was not associated with altered expression levels of hormone-sensitive lipase or perilipin. The acute insulin secretory response to beta-adrenergic stimulation was also profoundly suppressed in aP2-/- mice despite comparable total concentrations and only minor changes in the composition of systemic FFAs. To address whether levels of specific fatty acids are different in aP2-/- mice, the plasma FFA profile after beta-adrenergic stimulation was determined. Significant reduction in both stearic and cis-11-eicoseneic acids and an increase in palmitoleic acid were observed. The response of aP2-/- mice to other insulin secretagogues such as arginine and glyburide was similar to that of aP2+/+ mice, arguing against generally impaired function of pancreatic beta-cells. Finally, no aP2 expression was detected in isolated pancreatic islet cells. These results provide support for the existence of an adipo-pancreatic axis, the proper action of which relies on the presence of aP2. Consequently, aP2's role in the pathogenesis of type 2 diabetes might involve regulation of both hyperinsulinemia and insulin resistance through its impact on both lipolysis and insulin secretion. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |