The effect of endurance training with crocin consumption on the levels of MFN2 and DRP1 gene expression and glucose and insulin indices in the muscle tissue of diabetic rats

Abstract

This study aimed to investigate the effect of crocin consumption, high-intensity interval training (HIIT), and low-intensity continuous training (LICT) and their interactive effect on the gene expression of Mfn2 and Drp1 in the skeletal muscle and serum glucose and insulin indices in high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic rats. Fifty-six adult rats were divided into eight groups of seven subjects: crocin consumption, HIIT, LICT, HIIT with crocin, LICT with crocin, diabetic control, healthy control, and sham (placebo). At the end of the course (5 months), metabolic indices were measured. Moreover, the Mfn2 and Drp1 gene expression levels in all groups were measured using RT-PCR. The statistical analysis showed that in the exercise training (HIIT and LICT) and the crocin consumption groups, the glucose and insulin indices significantly improved (p = .005). Moreover, in these groups, the levels of gene expression of Mfn2 and Drp1 significantly increased and decreased, respectively (p = .001). Exercise training and crocin consumption appear to, either in combination or individually, have a beneficial effect on mitochondrial dynamics and diabetes by improving the mitochondrial fusion and fission indices (Mfn2 and Drp1), and by modifying the insulin resistance index and glucose homeostasis. Practical applicationsMfn2 and Drp1, as the main regulators of the mitochondrial fusion and fission, play an important role in maintaining mitochondrial dynamics and type 2 diabetes. Thus, the regulation of mitochondrial dynamics is an intricate process that retains the balance between mitochondrial fission and fusion, and any disturbance in this balance can lead to mitochondrial-associated diseases including insulin resistance and T2D. There is evidence that herbal antioxidants Including crocin and exercise training help improve the mitochondrial activity and insulin sensitivity in T2D. Considering the importance of the two Drp1 and Mfn1 genes in the mitochondrial dynamic pathway and coding the proteins that play a key role in relation to T2D, this study primarily examined the interactive effects of endurance training (HIIT and LICT) along with crocin consumption on the expression the genes mentioned above; the results obtained in this study can provide a new approach to the treatment of HFD + STZ-induced diabetic rats. K E Y W O R D Scrocin, Drp1, Mfn2, T2D, training

Diabetes Mellitus, Mitochondrial Dysfunction and Ca2+-Dependent Permeability Transition Pore

“…There is increasing evidence that altered insulin signaling in cells may contribute to changes in the level of proteins responsible for mitochondrial fusion and in the structure of the mitochondrial network. It has been shown that the expression of MFN2and OPA1 is significantly decreased in many tissues of diabetic animals [ 29 , 30 , 32 , 33 , 36 , 87 , 88 , 89 ]. Treatment with the mitochondrial fusion promoter-M1 increases the expression of OPA1, promotes mitochondrial fusion, enhances mitochondrial respiratory capacity, and reduces the rate of ROS production by mitochondria [ 90 ].…”

“…At the same time, the function of the mitochondrial fission machinery in diabetes is enhanced. In particular, increased expression of DRP1 and FIS1 is observed [ 28 , 30 , 31 , 32 , 33 , 34 , 87 , 89 ]. In cultured skeletal muscle cells and cortical neurons, genetic and pharmacological inhibition of Drp1 was shown to attenuate palmitate-induced mitochondrial fragmentation and insulin resistance [ 91 , 92 ].…”

Effects of high intensity interval exercise on cerebrovascular function: A systematic review

“…The search methods resulted in 67 articles. After removal of duplicates, 15[40-53] articles were identified in PubMed and 5[54-58] new articles in CINAHL. During the initial screening of titles/abstracts, 11 articles were excluded due to HIIE not being the primary experimental protocol performed (n=6), studies not measuring cerebral arteries (n=4) and an animal study (n=1).…”

The Effect of Endurance Training with Crocin Consumption on the Levels of AMPK and NRF1 Gene Expression in the Soleus Muscles of Diabetic Rats

“…LICT started in the first week at 25 minutes and reached 50 minutes in the last week. In addition, the whole size of training activities (severity, time, and repetition) was coordinated between the two groups of LICT and HIIT (11). Also, crocin utilization groups received 25 mg/kg of crocin (Sigma Company, USA) daily for eight weeks.…”

“…Also, crocin utilization groups received 25 mg/kg of crocin (Sigma Company, USA) daily for eight weeks. Crocin was administered intraperitoneally and dissolved in normal saline (11). To control the effects of crocin injection on the variables of the study, the sham group received crocin solvent intraperitoneally each day.…”