oxyntomodulin and Sarcopenia

Dulaglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, is widely used to treat diabetes. However, its effects on muscle wasting due to aging are poorly understood. In the current study, we investigated the therapeutic potential and underlying mechanism of dulaglutide in muscle wasting in aged mice. Dulaglutide improved muscle mass and strength in aged mice. Histological analysis revealed that the cross-sectional area of the tibialis anterior (TA) in the dulaglutide-treated group was thicker than that in the vehicle group. Moreover, dulaglutide increased the shift toward middle and large-sized fibers in both young and aged mice compared to the vehicle. Dulaglutide increased myofiber type I and type IIa in young (18.5% and 8.2%) and aged (1.8% and 19.7%) mice, respectively, compared to the vehicle group. Peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), a master regulator of mitochondrial biogenesis, decreased but increased by dulaglutide in aged mice. The expression of atrophic factors such as myostatin, atrogin-1, and muscle RING-finger protein-1 was decreased in aged mice, whereas that of the myogenic factor, MyoD, was increased in both young and aged mice following dulaglutide treatment. In aged mice, optic atrophy-1 (OPA-1) protein was decreased, whereas Toll-like receptor-9 (TLR-9) and its targeting inflammatory cytokines (interleukin-6 [IL-6] and tumor necrosis factor-α [TNF-α]) were elevated in the TA and quadriceps (QD) muscles. In contrast, dulaglutide administration reversed this expression pattern, thereby significantly attenuating the expression of inflammatory cytokines in aged mice. These data suggest that dulaglutide may exert beneficial effects in the treatment of muscle wasting due to aging.

Topics: Aging; Animals; Glucagon-Like Peptides; GTP Phosphohydrolases; Humans; Hypoglycemic Agents; Immunoglobulin Fc Fragments; Interleukin-6; Male; Mice; Muscle Proteins; Muscle, Skeletal; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Recombinant Fusion Proteins; Sarcopenia; Signal Transduction; SKP Cullin F-Box Protein Ligases; Toll-Like Receptor 9; Tumor Necrosis Factor-alpha

To evaluate the effect of dulaglutide on body composition in type 2 diabetes mellitus (T2DM) patients undergoing hemodialysis (HD).. Twenty-one T2DM patients on HD, who had been treated with insulin and newly added teneligliptin (N = 10) or dulaglutide (N = 11), were enrolled. Body composition changes, such as fat mass (FM) and skeletal muscle mass (SMM), glycated albumin (GA), and insulin doses were compared before and after six months of treatment with teneligliptin or dulaglutide.. The percentage changes of GA and insulin doses were comparable between the teneliglipin and dulaglutide groups. Conversely, although FM and SMM did not change in the teneligliptin group (from 15.7 kg to 14.1 kg, P = 0.63 and 18.6 kg to 18.9 kg, P = 0.16, respectively), those in the dulaglutide group significantly decreased (from 21.9 kg to 18.9 kg, P = 0.037 and 21.0 kg to 20.2 kg, P = 0.011, respectively).. Six months of dulaglutide treatment significantly reduced not only FM but also SMM, although changes in GA and insulin doses were comparable with those in the teneligliptin group. Dulaglutide may have the effect of promoting sarcopenia; therefore, it may be carefully used in T2DM patients on HD.

Topics: Aged; Body Composition; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Glucagon-Like Peptides; Humans; Immunoglobulin Fc Fragments; Male; Middle Aged; Pyrazoles; Recombinant Fusion Proteins; Renal Dialysis; Renal Insufficiency, Chronic; Sarcopenia; Thiazolidines