Dapagliflozin restores insulin and growth hormone secretion in obese mice

in Journal of Endocrinology
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  • 1 School of Biomedical Sciences, University of Queensland, St Lucia, Brisbane, Australia
  • 2 School of Information Technology and Electrical Engineering, University of Queensland, St Lucia, Brisbane, Australia
  • 3 Department of Physiology, Monash University, Melbourne, Australia
  • 4 Department of Medicine, Endocrine Research Unit, Mayo School of Graduate Medical Education, Clinical Translational Science Center, Mayo Clinic, Rochester, Minnesota, USA

Correspondence should be addressed to C Chen: chen.chen@uq.edu.au

*(Z Huang and L Huang contributed equally to this work)

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The well-documented hormonal disturbance in a general obese population is characterised by an increase in insulin secretion and a decrease in growth hormone (GH) secretion. Such hormonal disturbance promotes an increase in fat mass, which deteriorates obesity and accelerates the development of insulin resistance and type 2 diabetes. While the pathological consequence is alarming, the pharmaceutical approach attempting to correct such hormonal disturbance remains limited. By applying an emerging anti-diabetic drug, the sodium-glucose cotransporter 2 inhibitor, dapagliflozin (1 mg/kg/day for 10 weeks), to a hyperphagic obese mouse model, we observed a significant improvement in insulin and GH secretion as early as 4 weeks after the initiation of the treatment. Restoration of pathological disturbance of insulin and GH secretion reduced fat accumulation and preserved lean body mass in the obese animal model. Such phenotypic improvement followed with concurrent improvements in glucose and lipid metabolism, insulin sensitivity, as well as the expression of metabolic genes that were regulated by insulin and GH. In conclusion, 10 weeks of treatment with dapagliflozin effectively reduces hyperinsulinemia and restores pulsatile GH secretion in the hyperphagic obese mice with considerable improvement in lipid and glucose metabolism. Promising outcomes from this study may provide insights into drug intervention to correct hormonal disturbance in obesity to delay the diabetes progression.

Supplementary Materials

    • Table S1. qPCR primers sequences
    • Figure S1
    • Figure S2
    • Figure S3
    • Figure S4. Negative controls of the pancreas immunohistochemistry

 

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