Nateglinide, a non-sulfonylurea rapid insulin secretagogue, increases pancreatic islet blood flow in rats.
We studied whether the rapid hypoglycemic action of nateglinide is associated with an increase in islet blood flow. Islet blood flow was measured using the two-colour microsphere method. Orally administered nateglinide with glucose acutely increased islet blood flow to levels greater than those after glucose alone or tolbutamide with glucose in conscious Sprague-Dawley rats (percent increase at 10 min after oral administration; nateglinide+glucose, 125+/-25%; glucose, 33+/-11%, p<0.001; tolbutamide+glucose, 42+/-23%, p<0.01). Nateglinide administered with non-metabolisable 3-O-methylglucose also increased islet blood flow (61+/-17%). The stimulated islet blood flow significantly correlated with serum insulin levels. N(G)-monomethyl-L-arginine, a nitric oxide synthase inhibitor, completely inhibited the increase in islet blood flow induced by nateglinide with glucose. Intravenously administered nateglinide did not significantly affect the already increased islet blood flow in diabetic Otsuka Long-Evans Tokushima Fatty rats. Our results indicated that nateglinide acutely increased islet blood flow at least in part through a nitric oxide-dependent mechanism.
Iwase
Masanori
M
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. iwase@intmed2.med.kyushu-u.ac.jp
Nakamura
Udai
U
Uchizono
Yuji
Y
Nohara
Sakae
S
Sasaki
Nobuhiro
N
Sonoki
Kazuo
K
Iida
Mitsuo
M
D019325:3-O-Methylglucose / Q000008:administration & dosage / Q000494:pharmacology; D000284:Administration, Oral; D000758:Anesthesia; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003243:Consciousness; D003510:Cyclohexanes / Q000008:administration & dosage / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D041981:Gastrointestinal Tract / Q000098:blood supply / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D000077715:Nateglinide; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D020334:Rats, Inbred OLETF; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D014044:Tolbutamide / Q000008:administration & dosage / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology
D001786:Blood Glucose; D003510:Cyclohexanes; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D019325:3-O-Methylglucose; D019323:omega-N-Methylarginine; D000077715:Nateglinide; D010649:Phenylalanine; D014044:Tolbutamide; D019001:Nitric Oxide Synthase; D005947:Glucose