Protective effect of metformin in CD1 mice placed on a high carbohydrate-high fat diet.
A high carbohydrate-high fat (HC-HF) diet-associated with hyperinsulinemia has been previously reported to induce accelerated growth of prostate cancer in a xenograft model. High energy supply and insulin/insulin growth factor-1 axis are two of the mechanisms proposed. We hypothesize that metformin may have a protective effect against prostate cancer progression by affecting metabolisms associated with high energy intake. In the present study, animals were randomized into five groups, receiving a HC-HF diet with 50, 100, or 250mg/kg body weight (mg/kg) metformin in drinking water, a standard diet or HC-HF diet alone. Animals on the HC-HF diet developed obesity and insulin resistance. They had significantly higher body weight, fasting blood glucose at an upper level of normal range, higher insulin secretion and utilization, and fatty degeneration of the liver. Metformin at the doses employed significantly reduced food and water consumption; however, only a dose of 250mg/kg showed a significant reduction in body weight gain and suppression of gluconeogenesis as well remarkably reduced insulin secretion. There was no observed metformin-related hepato-toxicity in any of the groups. In summary, metformin at various doses exhibits protective effects on the metabolic disorder caused by the HC-HF diet with the most effective protection at a dose of 250mg/kg. These effects may explain its translational role relating to its anti-neoplastic potential.
Hou
Min
M
Division of Urology, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
Venier
Natalie
N
Sugar
Linda
L
Musquera
Mireia
M
Pollak
Michael
M
Kiss
Alex
A
Fleshner
Neil
N
Klotz
Laurence
L
Venkateswaran
Vasundara
V
D000818:Animals; D004032:Diet / Q000009:adverse effects*; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000009:adverse effects*; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D051379:Mice; D008815:Mice, Inbred Strains; D009765:Obesity / Q000150:complications; D011471:Prostatic Neoplasms / Q000209:etiology / Q000517:prevention & control*; D015430:Weight Gain / Q000187:drug effects
D004040:Dietary Carbohydrates; D004041:Dietary Fats; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin