Cilostazol, a phosphodiesterase inhibitor, improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty Rat, a model of spontaneous NIDDM.
OBJECTIVE
Angiotensin converting enzyme inhibitors and alpha1-adrenergic blockers improve insulin sensitivity, the mechanism of which was considered, at least in part, to be due to the increased blood flow to muscle. The present study aimed to clarify whether cilostazol, a phosphodiesterase inhibitor, improves insulin sensitivity in a model of spontaneous non-insulin dependent diabetes mellitus (NIDDM), Otsuka Long-Evans Tokushima Fatty (OLETF) rat.


METHODS
OLETF rats were divided into the two groups at the age of 16 weeks: the cilostazol-supplemented group (cilostazol 40 mg/kg/day) and the normal-diet group. As a non-diabetic control, we used Long-Evans-Tokushima-Otsuka rats (non-diabetic rats). Oral glucose tolerance test and hyperinsulinemic euglycemic clamp was performed at the ages of 23 and 25 weeks, respectively. Serum levels of lipids and leptin were measured.


RESULTS
Body weight and abdominal fat was increased in OLETF rats but cilostazol supplementation did not alter them. Insulin sensitivity, as measured by the hyperinsulinemic euglycemic clamp technique, was significantly decreased in OLETF rats (glucose infusion rate: 73.5 +/- 10.0 vs. 41.5 +/- 9.8 micromol/min/kg body weight, p < 0.01). Cilostazol supplementation improved insulin sensitivity partially but significantly 51.0 +/- 5.7 micromol/min/kg body weight, p < 0.05) in OLETF rats at 25 weeks of age, although it did not decrease serum levels of glucose, lipids or leptin. However, this effect was not observed in non-diabetic rats.


CONCLUSIONS
Cilostazol, which is used in diabetic patients for the treatment of obstructive disease of artery, is expected to have a beneficial effect on insulin sensitivity in NIDDM.
Nakaya
Y
Y
Department of Nutrition, School of Medicine, University of Tokushima, Tokushima City, Japan. nakaya@nutr.med.tokushima-u.ac.jp
Minami
A
A
Sakamoto
S
S
Niwa
Y
Y
Ohnaka
M
M
Harada
N
N
Nakamura
T
T
D000005:Abdomen; D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D000077407:Cilostazol; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D004032:Diet; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance; D007333:Insulin Resistance; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D051381:Rats; D020334:Rats, Inbred OLETF / Q000502:physiology*; D012016:Reference Values; D013777:Tetrazoles / Q000627:therapeutic use*
D001786:Blood Glucose; D010726:Phosphodiesterase Inhibitors; D013777:Tetrazoles; D000077407:Cilostazol