The sibutramine metabolite M2 improves muscle glucose uptake and reduces hepatic glucose output: preliminary data.
The satiety agent sibutramine acts in part through a primary amine metabolite, M2. To investigate whether M2 could affect glycaemia independently of satiety and weight loss, groups of normal mice received a single dose of M2 (1 or 10 mg/kg) and food was withheld. Compared with controls (who received vehicle only), M2 (10 mg/kg) decreased basal plasma glucose concentrations, with a maximal decrease of about 25% at 48 hours (p < 0.05). Soleus muscles were isolated from the mice at intervals: insulin-mediated glucose uptake by the muscles from controls progressively decreased over 24 hours whereas uptake was maintained by muscles from M2-treated mice. Hepatic gluconeogenesis was reduced about 40% by liver snips isolated from M2-treated mice after 24 hours (p < 0.05). These preliminary results suggest that the M2 metabolite of sibutramine can reduce glycaemia, maintain insulin-mediated muscle glucose uptake and reduce hepatic gluconeogenesis independently of satiety and weight loss.
Coletta
Dawn K
DK
Division of Diabetes, Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, USA. richardsond2@uthscsa.edu
Bates
Sarah H
SH
Jones
Robert B
RB
Bailey
Clifford J
CJ
D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects; D003503:Cyclobutanes / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005943:Gluconeogenesis / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D001067:Appetite Depressants; D001786:Blood Glucose; D003503:Cyclobutanes; D007004:Hypoglycemic Agents; D007328:Insulin; D005947:Glucose; C058254:sibutramine