Differential effects of sodium-glucose cotransporter 2 inhibitor and low-carbohydrate diet on body composition and metabolic profile in obese diabetic db/db mice

IntroductionTreatment using sodium-glucose cotransporter (SGLT) 2 inhibitor and low-carbohydrate diet (LCD) for obesity and type 2 diabetes are similar in terms of carbohydrate limitation. However, their mechanisms of action differ, and the effects on the body remain unclear. We investigated the eff...

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Published in:BMJ open diabetes research & care 2020-09, Vol.8 (1), p.e001303
Main Authors: Kusakabe, Toru, Yokota, Shigefumi, Shimizu, Mika, Inoue, Takayuki, Tanaka, Masashi, Ohue-Kitano, Ryuji, Muranaka, Kazuya, Yamakage, Hajime, Wada, Hiromichi, Hasegawa, Koji, Satoh-Asahara, Noriko
Format: Article
Language:English
Subjects:
Blood pressure
Body composition
Calories
Carbohydrates
Diabetes
Diet
Experiments
Glucose
Insulin
Insulin resistance
Liver
Metabolism
Musculoskeletal system
Obesity
Pancreas
Plasma
Rodents
Variance analysis
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Summary:IntroductionTreatment using sodium-glucose cotransporter (SGLT) 2 inhibitor and low-carbohydrate diet (LCD) for obesity and type 2 diabetes are similar in terms of carbohydrate limitation. However, their mechanisms of action differ, and the effects on the body remain unclear. We investigated the effects of SGLT2 inhibitor and LCD on body composition and metabolic profile using the db/db mouse model for obesity and type 2 diabetes.Research design and methodsEight-week-old male db/db mice were divided into four groups: mice receiving normal diet and vehicle or canagliflozin (Cana) administration and mice receiving LCD and vehicle or Cana administration for 8 weeks. Consumed calories were adjusted to be equal among the groups.ResultsBoth Cana administration and LCD feeding resulted in significant weight gain. Cana administration significantly decreased plasma glucose levels and increased plasma insulin levels with preservation of pancreatic β cells. However, LCD feeding did not improve plasma glucose levels but deteriorated insulin sensitivity. LCD feeding significantly reduced liver weight and hepatic triglyceride content; these effects were not observed with Cana administration. Combined treatment with LCD did not lead to an additive increase in blood β-ketone levels.ConclusionsSGLT2 inhibitors and LCD exert differential effects on the body. Their combined use may achieve better metabolic improvements in obesity and type 2 diabetes.
ISSN:2052-4897
2052-4897
DOI:10.1136/bmjdrc-2020-001303