120-OR: Dapagliflozin Increases Adiponectin and Its Receptors, and Reduces Inflammation and Ceramide Synthesis Enzymes in the Obese Prediabetic Dog
| Autor: | Morvarid Kabir, V. Sashi Gopaul, Hsiu-Chiung Yang, Cathryn M. Kolka, Richard N. Bergman |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Adiponectin business.industry Endocrinology Diabetes and Metabolism Insulin medicine.medical_treatment Adipose tissue Type 2 diabetes Streptozotocin medicine.disease chemistry.chemical_compound Endocrinology chemistry Internal medicine Adipocyte Internal Medicine medicine Lipolysis Dapagliflozin business medicine.drug |
| Zdroj: | Diabetes. 70 |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | Sodium glucose cotransporter-2 (SGLT2) inhibitors promote urinary glucose excretion, consequently reducing blood glucose. Previously we showed that 6 weeks of Dapagliflozin (Dapa) treatment improved insulin sensitivity and prevented weight gain. In addition, Dapa promoted adipose tissue (AT) beiging, lipolysis and decreased adipocyte size primarily in the visceral (VIS) depot in a canine model of mild type 2 diabetes. Little is known about the effects of Dapa on AT inflammation and ceramide synthesis in both the subcutaneous (SC) and VIS fat depots. Twelve dogs were fed a high fat diet for 6 weeks, then received a single low dose of streptozotocin (18.5mg/kg) to induce mild type 2 diabetes. Animals were then exposed to Dapa (n=6, 1.25mg/kg) or placebo (n=6) once per day for 6 weeks, while remaining on the high fat diet. At the end of the treatment, fasting plasma parameters were measured, and SC and VIS fat biopsies were obtained for molecular studies. Dapa increased adiponectin, adiponectin receptors 1 and 2 gene expression by 90%, 74% and 69% ( In conclusion, Dapa promoted adiponectin and its receptors, decreased inflammation and enzymes involved in ceramide synthesis mainly in the VIS depot. These changes were independent of fasting glucose and insulin. Thus, for the first time we are beginning to identify mechanisms by which Dapa enhances AT function in regulating energy homeostasis and improving AT inflammation in mild type 2 diabetes canine model. Disclosure M. Kabir: None. R. N. Bergman: None. V. Gopaul: None. H. Yang: Employee; Self; AstraZeneca. C. M. Kolka: Research Support; Self; AstraZeneca. Funding National Institutes of Health |
| Databáze: | OpenAIRE |
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