Glucose, insulin, insulin receptor subunits alpha and beta in normal and spontaneously diabetic and obese ob/ob and db/db infertile mouse testis and hypophysis.

BACKGROUND: Type 2 diabetes touches young subjects of reproductive age in epidemic proportion. This study assesses glucose, total InsulinT, Insulin2 and insulin receptor subunits alpha and beta in testis during mouse development then, in the spontaneously type 2 diabetes models associated with infertility db/db and ob/ob mice. IR-beta and alpha were also assessed in spermatozoa (SPZ), anterior pituitary (AP) and serum. METHODS: Serum and tissue glucose were measured with enzymatic colorimetric assays and InsulinT and Insulin2 by ELISAs in serum, interstitial tissue- (ITf) and seminiferous tubule (STf) fractions in14- > 60-day-old normal and db/db, ob/ob and wild type (WT) mice. IR subunits were assessed by immunoblotting in tissues and by immunoprecipitation followed by immunoblotting in serum. RESULTS: Development: Glucose increased in serum, ITf and STf. InsulinT and Insulin2 dropped in serum; both were higher in STf than in ITf. In > 60-day-old mouse ITf, insulinT rose whereas Insulin2 decreased; InsulinT and Insulin2 rose concurrently in STf. Glucose and insulin were high in > 60-day-old ITf; in STf high insulin2 accompanied low glucose. One hundred ten kDa IR-beta peaked in 28-day-old ITf and 14-day-old STf. One hundred thirty five kDa IR-alpha was high in ITf but decreased in STf. Glucose escalated in db/db and ob/ob sera. Glucose doubled in ITf while being halved in STf in db/db mice. Glucose significantly dropped in db/db and ob/ob mice spermatozoa. InsulinT and Insulin2 rose significantly in the serum, ITf and STf in db/db and ob/ob mice. One hundred ten kDa IR-beta and 135 kDa IR-alpha decreased in db/db and ob/ob ITf. Only 110 kDa IR-beta dropped in db/db and ob/ob STf and AP. One hundred ten kDa IR-beta fell in db/db and ob/ob SPZ. One hundred ten kDa sIR-alpha rose in the db/db and ob/ob mouse sera. CONCLUSION: Insulin regulates glucose in tubules not in the interstitium. The mouse interstitium contains InsulinT and Insulin2 whereas tubules contain Insulin2. Decreased 110 kDa IR-beta and 135 kDa IR-alpha in the db/db and ob/ob interstitial tissue suggest a loss of active receptor sites that could alter the testicular cell insulin binding and response to the hormone. Decreased IR-beta levels were insufficient to stimulate downstream effectors in AP and tubules. IR-alpha shedding increased in db/db and ob/ob mice.