Vasodilation of rat retinal microvessels induced by monobutyrin. Dysregulation in diabetes.
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.
Halvorsen
Y D
YD
Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Bursell
S E
SE
Wilkison
W O
WO
Clermont
A C
AC
Brittis
M
M
McGovern
T J
TJ
Spiegelman
B M
BM
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000818:Animals; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000503:physiopathology*; D005451:Fluorescein Angiography; D005989:Glycerides / Q000494:pharmacology*; D005990:Glycerol / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012171:Retinal Vessels / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D014664:Vasodilation
D043925:Angiogenesis Inducing Agents; D002087:Butyrates; D005989:Glycerides; D020148:Butyric Acid; C063895:1-butyrylglycerol; D006632:Histamine; D005990:Glycerol