title: Strontium fructose 1,6-diphosphate alleviates early diabetic testopathy by suppressing abnormal testicular matrix metalloproteinase system in streptozocin-treated rats.
abstract: OBJECTIVE
  Male hypogonadism is frequently associated with testopathy in patients with type 2 diabetes and in middle-aged males. We hypothesized that abnormal matrix metalloproteinases (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.
  
  
  RESULTS
  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 g-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.
authors.affiliation: College of Life Science and Pharmaceutical Engineering, Nanjing University of Technology, Nanjing, 210009, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Hao-Ran
authors.initials: HR
authors.lastname: Liu
authors.forename: Han-Jie
authors.initials: HJ
authors.lastname: Ying
authors.forename: De-Zai
authors.initials: DZ
authors.lastname: Dai
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Tang
authors.forename: Yin
authors.initials: Y
authors.lastname: Dai
mesh_terms: D000135:Acid Phosphatase / Q000037:antagonists & inhibitors / Q000097:blood; D000818:Animals; D048909:Diabetes Complications / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005635:Fructosediphosphates / Q000494:pharmacology*; D015870:Gene Expression; D006943:Hyperglycemia / Q000139:chemically induced; D007006:Hypogonadism / Q000150:complications / Q000188:drug therapy*; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors / Q000097:blood; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000145:classification / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000008:administration & dosage / Q000633:toxicity*; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors / Q000097:blood; D013737:Testis / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D013739:Testosterone / Q000037:antagonists & inhibitors / Q000097:blood; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors / Q000097:blood
chemical_list: D005635:Fructosediphosphates; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D013739:Testosterone; D013311:Streptozocin; D007770:L-Lactate Dehydrogenase; D013385:Succinate Dehydrogenase; D005723:gamma-Glutamyltransferase; D000135:Acid Phosphatase; D020782:Matrix Metalloproteinases; C029063:fructose-1,6-diphosphate