Strontium fructose 1,6-diphosphate alleviates early diabetic testopathy by suppressing abnormal testicular matrix metalloproteinase system in streptozocin-treated rats

Objectives Male hypogonadism is frequently associated with testopathy in patients with type 2 diabetes and in middle-aged males. We hypothesized that abnormal matrix metailoproteinases (MMPs) and their tissue inhibitors (TIMPs) in testis have large roles to play in male hypogonadism. It has been found in diabetic rats that a novel compound, strontium fructose 1,6-diphosphate (FDP-Sr), with extra high energy supply, could reverse male hypogonadism by normalizing MMP-9 and TIMPs in the testis. We investigated whether FDP-Sr could be promising in treating diabetic testopathy. Methods Adult male Sprague-Dawley rats were administered a single dose of streptozocin (65 mg/kg, i.p.) to induce diabetes. The diabetic rats were treated with FDP-Sr in three doses or testosterone propionate in the final four weeks during the eight-week study. Key findings Serum testosterone, activity of marker enzymes, and mRNA of MMPs and TIMPs and protein of MMP-9 in the testis were detected. After eight weeks, the activity of acid phosphatase, lactate dehydrogenase, succinate dehydrogenase and γ-glutamyl transpeptidase in testis were significantly decreased (P > 0.01), accompanied by down- regulated mRNA and activity of MMP-2 and MMP-9 (P > 0.01) and upregulated mRNA of TIMP-1 and TIMP-2. Downregulated MMP-9 protein and degenerative changes in histology were predominant in diabetic testis. Conclusions FDP-Sr or testosterone propionate significantly normalized expression and activity of the MMPs-TIMPs system to attenuate changes in serum testosterone, marker enzymes and histology in testis. Effects of FDP-Sr were dose-dependent and comparable with those of testosterone propionate. By supplying extra energy, FDP-Sr could be promising in treating diabetic testopathy by normalizing abnormal MMP-9 and its endogenous inhibitors in testes.