Comparison of voglibose and nateglinide for their acute effects on insulin secretion and free fatty acid levels in OLETF rat portal blood after sucrose loading.
OBJECTIVE
Short-term hypoglycemic effects of single dose voglibose and nateglinide were compared after sucrose loading in spontaneously diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats.


METHODS
After a 17-h fasting period, the animals received 0.06 mg/kg of voglibose (VOG group, n = 6), 50 mg/kg of nateglinide (NAT group, n = 6), or 0.5% methyl cellulose (control group, n = 6), immediately followed by 2.5 g/kg of sucrose.


RESULTS
Compared to control group values, glucose levels after sucrose loading were significantly decreased in the portal blood in the VOG group and in the peripheral blood in the NAT and VOG groups. The portal glucose AUC0-120 min was significantly lower in the VOG group than in the control and NAT groups, whereas the peripheral glucose AUC0-120 min was significantly lower in the VOG and NAT groups than in the control group. Portal insulin levels in the VOG group were significantly decreased compared to the control group. However, portal insulin levels in the NAT group were acutely increased, peaking 15 min after sucrose loading. Portal FFA levels were decreased in the NAT group 15, 30, and 60 min after sucrose loading; no FFA reductions were seen in the VOG group.


CONCLUSIONS
Although both drugs produced similar hypoglycemic effects after sucrose loading in the peripheral blood, these drugs generated vastly different results in portal blood. Reduced FFA in the portal blood, observed after single administration of nateglinide, may have a favorable impact not only on glucose metabolism but also on lipid metabolism.
Mori
Yutaka
Y
Department of Internal Medicine, National Higashi Utsunomiya Hospital, Kawachi-gun, Tochigi, Japan. moriyutakajp@yahoo.co.jp
Kitahara
Yoshirou
Y
Miura
Kyouko
K
Tajima
Naoko
N
D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D003510:Cyclohexanes / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007294:Inositol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology*; D011169:Portal Vein; D019518:Postprandial Period; D051381:Rats; D020334:Rats, Inbred OLETF; D012636:Secretory Rate / Q000187:drug effects; D013395:Sucrose / Q000008:administration & dosage* / Q000378:metabolism
D001786:Blood Glucose; D003510:Cyclohexanes; D004791:Enzyme Inhibitors; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D000077715:Nateglinide; D010649:Phenylalanine; D007294:Inositol; D013395:Sucrose; C102817:voglibose