title: Decreased blood glucose excursion by nateglinide ameliorated neuropathic changes in Goto-Kakizaki rats, an animal model of non-obese type 2 diabetes.
abstract: In the present study, we examined the effect of long-term suppression of postprandial hyperglycemia and glycemic fluctuation in Goto-Kakizaki (GK) rats, a type 2 diabetic animal model, by nateglinide (NG), a fast-acting hypoglycemic agent, on some measures of neuropathy and compared the outcome with the slow-acting effect of glibenclamide (GC). GK rats fed twice daily were given NG (50 mg/kg) or GC (1 mg/kg) orally before each meal for 24 weeks. The dose of NG and GC was determined by the data of their comparable suppressive effects on hyperglycemia as a total sum of glucose values after glucose load. At the end, there was no significant influence of treatment with NG or GC on body weight, fasting blood glucose, and glycated hemoglobin in GK rats. However, NG treatment suppressed postprandial hyperglycemia by 50% throughout the observation period, whereas this effect was not apparent in GC-treated rats. Delayed motor nerve conduction velocity was normalized by NG treatment, while GC had a partial (50%) effect. GK rats showed elevated contents of sorbitol and 3-deoxyglucosone in the sciatic nerve, and these changes were inhibited by NG treatment. Reduced Na(+)/K(+)-adenosine triphosphatase (ATPase) activity in GK rats was not affected by either NG or GC treatment. These results suggest that meticulous control of postprandial hyperglycemia is essential to inhibit the development of neuropathy in type 2 diabetes.
authors.affiliation: Pharmaceutical Research Laboratories, Ajinomoto, Kawasaki, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Kitahara
authors.forename: Kyoko
authors.initials: K
authors.lastname: Miura
authors.forename: Kaori
authors.initials: K
authors.lastname: Takesue
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Mine
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Wada
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Uchida
authors.forename: Satoru
authors.initials: S
authors.lastname: Ito
authors.forename: Soroku
authors.initials: S
authors.lastname: Yagihashi
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003510:Cyclohexanes / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000097:blood / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D005905:Glyburide / Q000494:pharmacology; D006442:Glycated Hemoglobin / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019518:Postprandial Period; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000378:metabolism; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D003510:Cyclohexanes; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000077715:Nateglinide; D010649:Phenylalanine