Chronic and acute effects of thiazolidinediones BM13.1258 and BM15.2054 onrat skeletal muscle glucose metabolism

Citation
C. Furnsinn et al., Chronic and acute effects of thiazolidinediones BM13.1258 and BM15.2054 onrat skeletal muscle glucose metabolism, BR J PHARM, 128(6), 1999, pp. 1141-1148
Citations number
32
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BRITISH JOURNAL OF PHARMACOLOGY
ISSN journal
00071188 → ACNP
Volume
128
Issue
6
Year of publication
1999
Pages
1141 - 1148
Database
ISI
SICI code
0007-1188(199911)128:6<1141:CAAEOT>2.0.ZU;2-0
Abstract
1 New thiazolidinediones BM13.1258 and BM15.2054 were studied with regard t o their PPAR gamma-agonistic activities and to their acute and chronic effe cts on glucose metabolism in soleus muscle strips from lean and genetically obese rats. 2 Both BM13.1258 and BM15.2054 revealed to be potent PPAR gamma-activators in transient transfection assays in vitro. 3 In insulin-resistant obese rats, but not in lean rats, 10 days of oral tr eatment with either compound increased the stimulatory effect of insulin on muscle glycogen synthesis to a similar extent (insulin-induced increment i n mu mol glucose incorporated into glycogen g(-1) h(-1): control, + 1.19 +/ - 0.28; BM13.1258, + 2.50 +/- 0.20; BM15.2054, + 2.55 +/- 0.46; P < 0.05 vs control each). 4 In parallel to insulin sensitization, mean glucose oxidation increased in sulin-independently in response to BM13.1258 (to 191 and 183% of control in the absence and presence of insulin, respectively; P < 0.01 each), which w as hardly seen in response to BM15.2054 (to 137 and 124% of control, respec tively; ns). 5 Comparable effects on PPAR gamma activation and on amelioration of insuli n resistance by BM13.1258 and BM15.2054 were therefore opposed by different effects on glucose oxidation. 6 In contrast to chronic oral treatment, acute exposure of muscles to BM13. 1258 or BM15.2054 in vitro elicited a distinct catabolic response of glucos e metabolism in specimens from both lean and obese rats. 7 The results provide evidence that BM13.1258 and BM15.2054 can affect musc le glucose metabolism via more than one mechanism of action. 8 Further efforts are required to clarify, to what extent the activation of PPAR gamma are involved sensitization via thiazolidinediones. other mechan isms besides insulin in the antidiabetic actions of thiazolidinediones.