Exploring the potential therapeutic effect of heat-killed mycobacterium aurum on glycemic management and glucose metabolism in streptozotocin-induced diabetic BALB/c mice

Abstract

In the past few years, there has been a heightened interest in exploiting the immunomodulatory properties of mycobacteria to manage diabetes. In this context, Bacillus Calmette-Guerin (BCG), the live attenuated strain of Mycobacterium bovis, has been reported to optimize glycemic control in patients with type 1 diabetes and to reduce hyperglycemia in several experimental animal models of diabetes. Lately, heat-killed (HK) Mycobacterium aurum (M. aurum) was developed as a natural supplement with a capacity to reduce or prevent stress-induced inflammation; however, its bioactive properties are yet to be revealed. Therefore, our current study aimed to evaluate the therapeutic anti-diabetic potential of HK M. aurum in streptozotocin (STZ)-induced diabetic mice. Male BALB/c mice were divided into 3 groups: the vehicle group (CB + BBS) received one dose (intraperitoneal administration) of citrate buffer (CB) followed by 6 doses (intradermal administration) of borate buffer saline (BBS) , the untreated diabetic group (STZ + BBS) was injected with a single high dose (150 mg/Kg) (intraperitoneal administration) of STZ followed by 6 doses of BBS, and the treated diabetic group (STZ + HK M. aurum) received a single high dose (150 mg/Kg) (intraperitoneal administration) of STZ followed by 6 doses of HK M. aurum. Body weight, glycemia, and urine glucose were measured on a weekly basis. At week 6, all mouse groups were evaluated for their serum insulin levels using ELISA as well as for their liver catalase (CAT), lactate dehydrogenase (LDH), uncoupling protein 2 (UCP2) and skeletal muscle LDH, UCP3 and GLUT4 protein expression levels by western blot. Administration of HK M. aurum to normal non-diabetic mice did not result in significant alterations in their blood glucose levels. We also found that HK M. aurum-treated diabetic mice exhibited lower blood glucose levels and higher serum insulin levels as compared to untreated diabetic mice. Treatment of diabetic mice with 6 doses of HK M. aurum restored the altered protein expression levels of their liver UCP2 and LDH as well as of their skeletal muscle UCP3 and LDH. Our findings demonstrate a novel ability for HK M. aurum to lower hyperglycemia and to ameliorate dysregulated expression of metabolism-related proteins in STZ-induced diabetic mice. In conclusion, these results suggest that HK M. aurum can be used as a potential therapeutic agent for the management of diabetes.