Irisin is a hormone secreted by skeletal muscle following physical activity or excess of saturated fatty acids, able to promote energy expenditure and improve metabolic homeostasis. Serum irisin levels are reduced in type 2 diabetes (T2D), while exogenous irisin administration improves glycemic control in diabetic mice. We have previously demonstrated that irisin promotes beta-cell viability and insulin secretory function. This study investigated serum irisin levels in T2D patients according to their antidiabetes treatment. 127 T2D patients were enrolled and stratified by antidiabetes therapy: diet only (17); metformin only (met, 37); met plus sulfonylureas (5); met plus pioglitazone (7); met plus GLP-1 receptor agonists (GLP-1RAs, 31); met plus DPP-4 inhibitors (DPP-4i, 15); and met plus SGLT2 inhibitors (SGLT2i, 15). The control group included 36 sex-, and BMI-matched subjects without diabetes. T2D patients showed lower irisin levels than controls (21.5 [10.1-50.8] vs. 29.1 [14.1-43.5] ng/mL, P<0.01). Serum irisin levels were positively associated with diabetes duration (r=0.214, P<0.05) and negatively associated with total (r=-0.196, P<0.05) and LDL cholesterol (r=-0.214, P<0.05). Patients treated with met plus GLP-1RAs or DPP-4i showed increased serum irisin levels (28.1 [12.4-50.8] and 25.8 [13.2-37.8] ng/mL, respectively) compared to patients treated with diet or met (19.8 [13.5-40.5] and 16.9 [10.7-28.8] ng/ml, respectively; P<0.05), or with other diabetes therapies. Interestingly, in vitro treatment of human skeletal muscle cells with 10 nM exendin-4 resulted in enhanced irisin release in the culture medium compared to control.

In conclusion, in T2D GLP-1-based therapies significantly increase serum irisin to levels comparable to those of nondiabetic subjects, possibly through GLP-1 receptor-mediated stimulation of irisin release by skeletal muscle cells. Irisin may thus represent a new factor in the mechanism of action of GLP-1-based therapies.

Disclosure

A. Natalicchio: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Sanofi. S. Perrini: None. L. Laviola: Advisory Panel; Self; A. Menarini Diagnostics, Abbott, AstraZeneca, Lilly Diabetes, Novo Nordisk Inc., Roche Diabetes Care, Sanofi-Aventis, Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Medtronic. F. Giorgino: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk, Roche Diabetes Care, Sanofi, Research Support; Self; Lilly Diabetes, Roche Diabetes Care. N. Marrano: None. G. Biondi: None. A. Montedoro: None. G. Le grazie: None. L. Di gioia: None. F. Guarini: None. A. Borrelli: None. A. Cignarelli: None.

Funding

European Union–European Social Fund; PON R&I (2014-2020); AIM (1810057)

© 2021 by the American Diabetes Association
2021
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