Four weeks SGLT2 inhibition improves beta cell function and glucose tolerance without affecting muscle free fatty acid or glucose uptake in subjects with type 2 diabetes.

Autor: Voigt JH; Steno Diabetes Center Aarhus, Aarhus, Denmark., Lauritsen KM; Steno Diabetes Center Aarhus, Aarhus, Denmark.; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.; Danish Diabetes Academy, Odense University Hospital, Odense, Denmark., Pedersen SB; Steno Diabetes Center Aarhus, Aarhus, Denmark.; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark., Hansen TK; Steno Diabetes Center Aarhus, Aarhus, Denmark., Møller N; Steno Diabetes Center Aarhus, Aarhus, Denmark.; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark., Jessen N; Steno Diabetes Center Aarhus, Aarhus, Denmark.; Department of Biomedicine, Aarhus University, Aarhus, Denmark., Laurenti MC; Endocrine Research Unit, Department of Endocrinology, Diabetes and Nutrition, Mayo Clinic, Rochester, Minnesota, USA., Dalla Man C; Department of Information Engineering, University of Padua, Padua, Italy., Vella A; Endocrine Research Unit, Department of Endocrinology, Diabetes and Nutrition, Mayo Clinic, Rochester, Minnesota, USA., Gormsen LC; Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark., Søndergaard E; Steno Diabetes Center Aarhus, Aarhus, Denmark.; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.; Danish Diabetes Academy, Odense University Hospital, Odense, Denmark.; Endocrine Research Unit, Department of Endocrinology, Diabetes and Nutrition, Mayo Clinic, Rochester, Minnesota, USA.
Jazyk: angličtina
Zdroj: Basic & clinical pharmacology & toxicology [Basic Clin Pharmacol Toxicol] 2024 May; Vol. 134 (5), pp. 643-656. Date of Electronic Publication: 2024 Feb 26.
DOI: 10.1111/bcpt.13991
Abstrakt: Aims: Sodium glucose co-transporter-2 (SGLT2) inhibition lowers glucose levels independently of insulin, leading to reduced insulin secretion and increased lipolysis, resulting in elevated circulating free fatty acids (FFAs). While SGLT2 inhibition improves tissue insulin sensitivity, the increase in circulating FFAs could reduce insulin sensitivity in skeletal muscle and the liver. We aimed to investigate the effects of SGLT2 inhibition on substrate utilization in skeletal muscle and the liver and to measure beta-cell function and glucose tolerance.
Methods: Thirteen metformin-treated individuals with type 2 diabetes were randomized to once-daily empagliflozin 25 mg or placebo for 4 weeks in a crossover design. Skeletal muscle glucose and FFA uptake together with hepatic tissue FFA uptake were measured using [ 18 F]FDG positron emission tomography/computed tomography (PET/CT) and [ 11 C]palmitate PET/CT. Insulin secretion and action were estimated using the oral minimal model.
Results: Empagliflozin did not affect glucose (0.73 ± 0.30 vs. 1.16 ± 0.64, μmol/g/min p = 0.11) or FFA (0.60 ± 0.30 vs. 0.56 ± 0.3, μmol/g/min p = 0.54) uptake in skeletal muscle. FFA uptake in the liver (21.2 ± 10.1 vs. 19 ± 8.8, μmol/100 ml/min p = 0.32) was unaffected. Empagliflozin increased total beta-cell responsivity (20 ± 8 vs. 14 ± 9, 10 -9  min -1 , p < 0.01) and glucose effectiveness (2.6 × 10 -2  ± 0.3 × 10 -2 vs. 2.4 × 10 -2  ± 0.3 × 10 -2 , dL/kg/min, p = 0.02).
Conclusions: Despite improved beta-cell function and glucose tolerance, empagliflozin does not appear to affect skeletal muscle FFA or glucose uptake.
(© 2024 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)
Databáze: MEDLINE
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