NDLI: Actions of novel antidiabetic thiazolidinedione, T-174, in animal models of non-insulin-dependent diabetes mellitus (NIDDM) and in cultured muscle cells

Content Provider	PubMed Central
Author	Arakawa, Kenji Ishihara, Tomomi Aoto, Masamichi Inamasu, Masanori Saito, Akira Ikezawa, Katsuo
Copyright Year	1998
Abstract	The antihyperglycaemic effect and the possible mechanism of action of T-174, a novel thiazolidinedione derivative, was determined in vivo and in vitro. Oral administration of T-174 markedly improved hyperglycaemia, hyperinsulinaemia, hyperlipidaemia, and glucose intolerance in genetically obese and diabetic yellow KK (KK-Ay) mice (0.2–15.5 mg kg−1 day−1, for 7 days) and Zucker fatty rats (1.4–11.4 mg kg−1 day−1, for 6 days). The ED50 values for the glucose lowering action of T-174 and pioglitazone, another thiazolidinedione antidiabetic, were 1.8 and 29 mg kg−1 day−1, respectively in KK-Ay mice; T-174 was about 16 times more potent than pioglitazone. The hypoglycaemic effect of exogenous insulin in KK-Ay mice was enhanced after the administration of T-174. A hyperinsulinaemic euglycaemic clamp study in Zucker fatty rats showed an amelioration of whole-body insulin resistance by the T-174 treatment. Insulin-stimulated glucose metabolism was enhanced in adipocytes from KK-Ay mice treated with T-174. The insulin receptor number of the adipocytes was increased without a change in the affinity of the receptor. The hypomagnesaemia in KK-Ay mice was completely restored by T-174. In cultured L6 myotubes, glucose consumption and [3H]-2-deoxy-glucose transport were enhanced by T-174 (EC50; 6 and 4 μM, respectively). Combination of insulin with T-174 was additive to stimulate glucose disposal. These results suggest that the antihyperglycaemic effect of T-174 was mediated by enhanced insulin action. This was associated with amelioration of the hypomagnesaemia and T-174 directly increased basal and insulin-stimulated glucose utilization by cultured muscle cells.
Related Links	http://dx.doi.org/10.1038/sj.bjp.0702066
Ending Page	436
Page Count	8
Starting Page	429
File Format	PDF
ISSN	00071188
Journal	British Journal of Pharmacology
Issue Number	3
Volume Number	125
Language	English
Publisher Date	1998-10-01
Access Restriction	Open
Subject Keyword	Pharmacology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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