VASODILATION OF RAT RETINAL MICROVESSELS INDUCED BY MONOBUTYRIN - DYSREGULATION IN DIABETES

被引:16
作者
HALVORSEN, YDC
BURSELL, SE
WILKISON, WO
CLERMONT, AC
BRITTIS, M
MCGOVERN, TJ
SPIEGELMAN, BM
机构
[1] HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115
[2] HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115
[3] HARVARD UNIV,SCH MED,BEETHAM EYE INST,BOSTON,MA 02115
[4] HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115
[5] HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02115
关键词
ADIPOCYTE; ANGIOGENESIS; DIABETES; LIPID; VASODILATION;
D O I
10.1172/JCI116908
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
1-Butyryl-glycerol (monobutyrin) is a simple lipid product of adipocytes with angiogenic activity. Recent studies have shown that the biosynthesis of this compound is tightly linked to lipolysis, a process associated with changes in blood flow. We now present data indicating that monobutyrin is an effective vasodilator of rodent blood vessels using a fluorescent retinal angiogram assay. The vasodilatory activity of monobutyrin is potent (ED50 = 3.3 x 10(-7) M), dose dependent, and stereospecific. Because diabetes represents a catabolic, lipolytic state with numerous vascular complications, we examined the action and regulation of monobutyrin in insulin-deficient diabetic rats. Serum levels of monobutyrin in streptozotocin-induced diabetic rats were greatly elevated compared to normal animals. At the same time, the retinal vessels of the diabetic animals develop a resistance to the vasodilatory activity of monobutyrin. These results demonstrate a role for monobutyrin in the control of vascular tone and suggest a possible involvement in the pathology of diabetes.
引用
收藏
页码:2872 / 2876
页数:5
相关论文
共 25 条
[1]   RETINAL MICROCIRCULATION IN PATIENTS WITH DIABETES-MELLITUS - DYNAMIC AND MORPHOLOGICAL ANALYSIS OF PERIFOVEAL CAPILLARY NETWORK [J].
AREND, O ;
WOLF, S ;
JUNG, F ;
BERTRAM, B ;
POSTGENS, H ;
TOONEN, H ;
REIM, M .
BRITISH JOURNAL OF OPHTHALMOLOGY, 1991, 75 (09) :514-518
[2]   EVALUATING RETINAL CIRCULATION USING VIDEO FLUORESCEIN ANGIOGRAPHY IN CONTROL AND DIABETIC RATS [J].
BURSELL, SE ;
CLERMONT, AC ;
SHIBA, T ;
KING, GL .
CURRENT EYE RESEARCH, 1992, 11 (04) :287-295
[3]  
CASTELLOT JJ, 1982, P NATL ACAD SCI-BIOL, V79, P5597, DOI 10.1073/pnas.79.18.5597
[4]   HEPARIN POTENTIATION OF 3T3-ADIPOCYTE STIMULATED ANGIOGENESIS - MECHANISMS OF ACTION ON ENDOTHELIAL-CELLS [J].
CASTELLOT, JJ ;
KAMBE, AM ;
DOBSON, DE ;
SPIEGELMAN, BM .
JOURNAL OF CELLULAR PHYSIOLOGY, 1986, 127 (02) :323-329
[5]   POTENT STIMULATION OF VASCULAR ENDOTHELIAL CELL-GROWTH BY DIFFERENTIATED 3T3 ADIPOCYTES [J].
CASTELLOT, JJ ;
KARNOVSKY, MJ ;
SPIEGELMAN, BM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1980, 77 (10) :6007-6011
[6]   PLASMA-RENIN ACTIVITY AND HYPERTENSION IN DIABETES-MELLITUS [J].
CHRISTLIEB, AR ;
KALDANY, A ;
DELIA, JA .
DIABETES, 1976, 25 (10) :969-974
[7]  
CLERMONT A, 1992, INVEST OPHTH VIS SCI, V33, P1366
[8]  
CLERMONT A, 1989, IEEE ENG MED BIOL SO, V11, P1630
[9]   1-BUTYRYL-GLYCEROL - A NOVEL ANGIOGENESIS FACTOR SECRETED BY DIFFERENTIATING ADIPOCYTES [J].
DOBSON, DE ;
KAMBE, A ;
BLOCK, E ;
DION, T ;
LU, H ;
CASTELLOT, JJ ;
SPIEGELMAN, BM .
CELL, 1990, 61 (02) :223-230
[10]  
FRIEDMAN EA, 1990, DIABETES MELLITUS TH, P684