Advanced Glycation Endproduct in Soleus Muscle of Diabetic Sedentary and Diabetic, Endurance-trained Rats

Abstract

Carboxymethyl-lysine (CML) is an advanced glycation end product (AGE), the accumulation of which has been implicated in the etiology of diabetes complications. The presence of CML is related to the binding of sugars to proteins or lipids, and also is a marker of oxidative stress. It has previously been shown that the contractile properties of skeletal muscle are altered in animal models of diabetes. Immunohistochemistry has also identified increased accumulation of CML in theplantaris muscles of diabetic animals. Aim: This study aims to further explore the accumulation of CML in diabetic animals with and without insulin, and with endurance training. METHODS: Animals were randomly divided into control and diabetes groups, and into sedentary and trained subgroups (DNI-diabetes/no insulin, DS-diabetes sedentary, DE-diabetes exercise, CS-control sedentary, CE-control exercise). Diabetes was induced by intravenous administration of streptozotocin. The sedentary animals were allowed their usual cage-based activity. One diabetes group was not given insulin (DNI), the other two diabetes groups received insulin. The exercise groups ran on a treadmill for 5 days/week at 27 m/min. The experimental period was 12 weeks. At the end of the experimental period the animals were sacrificed; the soleus muscle was excised and snap-frozen in liquid nitrogen. Muscle cross-sections were immunolabelled for CML. Muscle fibers labelling for CML were then quantified. RESULTS: Immuno labelling for CML was quantified as follows (expressed as percentage of total number of myofibers counted): DNI: 25.3%, CS: 4.1 %, DS: 4.6%, CE: 4.3%, DE: 3.2%. CONCLUSION: The greatest accumulation of AGE was in the soleus of the DNI group, and may be linked to the severity of disordered glucose metabolism, and/or to increased oxidative stress. The quantities of CML immunolabelling in the other diabetes groups were significantly lower than in the DNI group. This result appears to be related to the administration of insulin, which influences both glucose and protein metabolism. Since the amount of CML immunolabelling was similar between DS and DE groups, it appears that insulin may have a greater effect on CML accumulation than does endurance exercise.