title: Exercise adds to metformin and acarbose efficacy in db/db mice.
abstract: Physical exercise is frequently recommended for the treatment of type 2 diabetes, whether as primary therapy with diet modification or as an adjunct to drug therapy. We hypothesized that mild exercise would enhance the glucose-lowering effects of 2 oral antihyperglycemic drugs, metformin and acarbose, in an animal model of type 2 diabetes. Eight-week-old male C57BL/Ks (db/db) mice were sorted into control and exercise groups and dosed daily for 4 weeks with vehicle, metformin (150 mg/kg/d), or acarbose (40 mg/kg/d). Exercise consisted of swimming (initially 5 min/d and ultimately 1 h/d for the last 2 weeks). Exercise, metformin, and acarbose independently reduced serum glucose concentrations 15% to 25% compared with the respective controls (P <.0001), but the effect on glucose concentration of combining drug therapy with exercise was no greater than the sum of the individual effects. Exercise training independently increased muscle glycogen (30%; P <.05) and liver glycogen (250%; P <.05) levels and slightly reduced serum high-density lipoprotein cholesterol (-8%; P <.05), whereas drug treatment had no effect on these variables. In addition, exercise but not drug treatment prevented the approximately 30% decline in serum insulin concentrations that occurred in the control animals (P <.05). Twenty-four hours after the last drug or exercise treatment, oral glucose tolerance and hemoglobin A1c were not significantly different between groups. Treatment also did not greatly affect triglyceride, glycerol, or total cholesterol concentrations. In conclusion, exercise and drug therapy independently decreased serum glucose in db/db mice, and these effects did not appear to be synergistic. In addition, exercise training maintained serum insulin concentrations and increased tissue glycogen storage. These results suggest that exercise has the potential to add to the efficacy of oral antihyperglycemic drugs.
authors.affiliation: Shaman Pharmaceuticals, Inc, South San Francisco, CA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Tang
authors.forename: M J
authors.initials: MJ
authors.lastname: Reed
mesh_terms: D020909:Acarbose / Q000627:therapeutic use*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D004195:Disease Models, Animal; D004435:Eating; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018482:Muscle, Skeletal / Q000378:metabolism; D005082:Physical Exertion / Q000502:physiology; D013550:Swimming; D016896:Treatment Outcome
chemical_list: D020909:Acarbose; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D006003:Glycogen; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D008687:Metformin