Glucose In Tubules Research Articles

PCSK9 Contributes to the Cholesterol, Glucose, and Insulin2 Homeostasis in Seminiferous Tubules and Maintenance of Immunotolerance in Testis.

The PCSK9 contribution to cholesterol and immunotolerance homeostasis and response to glucose, and insulin in testis and hypophysis were studied using Pcsk9-deficient (−/−) and transgenic [Tg (PCSK9)] mice, and diabetic, obese ob/ob and db/db mice. The spermatids/spermatozoa acrosome, peritubular vessels, and epididymal adipocytes were PCSK9- and LDL-R-positive. The pro-PCSK9/PCSK9 ratio was high in interstitial tissue-fractions (ITf) and spermatozoa and low in seminiferous tubule-fractions (STf) in normal adult mice. This ratio decreased in ITf in ob/ob and db/db mice but increased in tubules in ob/ob mice. Deleting pcsk9 lowered cholesterol in serum but increased testicular cholesterol. Furthermore, HMGCoA-red, ACAT-2 and LDL-R turnover increased whereas SR-BI decreased in ITf; in tubules, ABCA1 decreased and 160 kDa LDL-R increased in Pcsk9 −/− mice. Excess testicular cholesterol could result from increased cholesterol synthesis and uptake with reduction in SR-BI-mediated efflux in ITf and from the overload of apoptotic cells, lowered ABCA1-mediated efflux and stimulated LDL-R protein synthesis in tubules in Pcsk9 −/− mice. Concomitantly with the cholesterol accumulation, tubules showed infiltrates of immune cells, elevated IL-17A and IL-17RA, and changes in the immunotolerance homeostasis. PCSK9 deficiency decreased glucose in tubules and spermatozoa while increasing insulin2 in ITf and tubules not serum. Moreover, IR-α, and IR-β augmented in tubules but decreased in the anterior pituitary; IR-α increased whereas IR-β decreased in ITf. The histology and cholesterol levels were normal in Tg (PCSK9) mouse testis. The excess cholesterol creates a milieu favorable to the action of high IL-17A and IL-17RA, the development of inflammatory conditions and self-tolerance breakdown in testis.

Glucose, insulin, insulin receptor subunits \u03b1 and \u03b2 in normal and spontaneously diabetic and obese ob/ob and db/db infertile mouse\xa0testis and hypophysis

BackgroundType 2 diabetes touches young subjects of reproductive age in epidemic proportion. This study assesses glucose, total InsulinT, Insulin2 and insulin receptor subunits α and β in testis during mouse development then, in the spontaneously type 2 diabetes models associated with infertility db/db and ob/ob mice. IR-β and α were also assessed in spermatozoa (SPZ), anterior pituitary (AP) and serum.MethodsSerum 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.ResultsDevelopment: 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-β peaked in 28-day-old ITf and 14-day-old STf. One hundred thirty five kDa IR-α 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-β and 135 kDa IR-α decreased in db/db and ob/ob ITf. Only 110 kDa IR-β dropped in db/db and ob/ob STf and AP. One hundred ten kDa IR-β fell in db/db and ob/ob SPZ. One hundred ten kDa sIR-α rose in the db/db and ob/ob mouse sera.ConclusionInsulin regulates glucose in tubules not in the interstitium. The mouse interstitium contains InsulinT and Insulin2 whereas tubules contain Insulin2. Decreased 110 kDa IR-β and 135 kDa IR-α 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-β levels were insufficient to stimulate downstream effectors in AP and tubules. IR-α shedding increased in db/db and ob/ob mice.