Lactate-induced autophagy activation: unraveling the therapeutic impact of high-intensity interval training on insulin resistance in type 2 diabetic rats

• Published in: Scientific reports Vol. 14; no. 1; pp. 1108 - 11
• Main Authors: Pirani, Hossein, Soltany, Afsaneh, Hossein Rezaei, Maryam, Khodabakhshi Fard, Adeleh, Nikooie, Rohollah, Khoramipoor, Kimya, Chamari, Karim, Khoramipour, Kayvan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11-01-2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/443; 631/80; Animal models; Animals; Autophagy; Autophagy - physiology; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - therapy; Disease control; Extracellular signal-regulated kinase; Glucose; High fat diet; High-Intensity Interval Training; Humanities and Social Sciences; Insulin; Insulin Resistance; Interval training; Kinases; Lactic Acid; Male; Mammals - metabolism; Microtubule-associated protein 1; multidisciplinary; Protein kinase; Proteins; Pyruvates; Pyruvic acid; Rapamycin; Rats; Rats, Wistar; Ribosomal protein S6; Ribosomal protein S6 kinase; Ribosomal Protein S6 Kinases, 70-kDa - metabolism; Science; Science (multidisciplinary); Serum levels; Signal transduction; Soleus muscle; Streptozocin; TOR protein; TOR Serine-Threonine Kinases - metabolism; Training
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-50589-0

Impaired autophagy is a hallmark of diabetes. The current study proposed to investigate if high intensity interval training (HIIT) induced lactate accumulation could stimulate autophagy in type 2 diabetic male rats. 28 male Wistar rats were randomly assigned into four groups: Healthy Control (CO), Diabetes Control (T2D), Exercise (EX), and Diabetes + Exercise (T2D + EX). Diabetes was induced by feeding high-fat diet and administrating single dose of streptozotocin (35 mg/kg). After becoming diabetic, the animals in the exercise groups (EX and T2D + EX) performed an eight-week HIIT (4–10 interval, 80–100% Vmax, 5 days per week). Serum levels of lactate, glucose and insulin as well as the levels of lactate, pyruvate, lactate transporter monocarboxylate transporter 1 (MCT1), phosphorylated mitogen-activated protein kinases (p-MAP 1 and 2), phosphorylated extracellular signal-regulated protein kinases 1 and 2 (p-ERK 1 and 2), mammalian target of rapamycin (p-mTOR), ribosomal protein S6 kinase beta-1 (p-70S6k), p90 ribosomal S6 kinases (p-90RSK), autophagy related 7 (ATG7), Beclin-1, microtubule-associated protein 1A/1B, and 2A/2B -light chain 3 levels (LC3-I), (LC3- II), (LC3I/LC3II) in soleus muscle were measured. Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and serum glucose was lower in T2D + EX compared to T2D group (
P
 < 0.0001). While serum and soleus muscle levels of lactate was not different between T2D and T2D + Ex, the levels of Pyruvate (
P
 < 0.01), MCT1, p-ERK1/2, p-mTOR, p70S6k, P-90RSK, ATG7, LC3-II, and LC3-II/LC3I ratios were higher in T2D + EX compared to T2D group (
P
 < 0.0001). We concluded that eight weeks of high-intensity interval training could activated ERK/P90SRK while inhibiting mTOR/P70S6K signaling pathway in lactate dependent manner. It means increased autophagy which resulted in improve insulin resistance (IR) and reduce blood glucose.