Glucose, insulin, insulin receptor subunits α and β in normal and spontaneously diabetic and obese ob/ob and db/db infertile mouse testis and hypophysis

Abstract

Background: Type 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. 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-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.

Cx30.2 deletion causes imbalances in testicular Cx43, Cx46, and Cx50 and insulin receptors. Reciprocally, diabetes/obesity alters Cx30.2 in mouse testis

“…Cx43 and Cx50 are upregulated while Cx46 is downregulated in the db/db mouse tubules, whereas the opposite occurs in the interstitial tissue (46). Whether the excess of glucose we measured (46,50) in the diabetic and obese ob/ob and db/db mice alters Cx30.2 in testes is unknown. In the normal mouse, insulin regulates glucose in tubules not in the interstitium (50).…”

“…Whether the excess of glucose we measured (46,50) in the diabetic and obese ob/ob and db/db mice alters Cx30.2 in testes is unknown. In the normal mouse, insulin regulates glucose in tubules not in the interstitium (50). Furthermore, the mouse interstitium contains Insulin Total and Insulin2, whereas tubules contain Insulin2 (50).…”

“…In the normal mouse, insulin regulates glucose in tubules not in the interstitium (50). Furthermore, the mouse interstitium contains Insulin Total and Insulin2, whereas tubules contain Insulin2 (50). The db/db and ob/ob mouse interstitial tissue is characterized by decreased 110-kDa insulin receptors (IR) subunit ␤ (IR␤) and 135-kDa IR␣ subunit levels (50), which suggest a loss of active receptor sites prone to alter the testicular cell insulin binding and response to the hormone and glucose uptake.…”

“…Furthermore, the mouse interstitium contains Insulin Total and Insulin2, whereas tubules contain Insulin2 (50). The db/db and ob/ob mouse interstitial tissue is characterized by decreased 110-kDa insulin receptors (IR) subunit ␤ (IR␤) and 135-kDa IR␣ subunit levels (50), which suggest a loss of active receptor sites prone to alter the testicular cell insulin binding and response to the hormone and glucose uptake. In an attempt to identify Cx30.2 effect on glucose metabolism, we probed the impact of Cx30.2 deficiency on IR subunits ␣ and ␤, the activators of the glucose metabolism signaling pathways in the Cx30.2Ϫ/Ϫ mouse testis.…”

Synbiotic Supplementation Modulates Gut Microbiota, Regulates Beta-catenin Expression and Prevents Weight Gain in Ob/ob Mice

“…The leptin de ciency causing hyperphagia, excessive nutrient intake and reduced energy expenditure leading to the development of MetS, with visceral obesity, IR, mimetizing obesity as well in humans [10]. Due to this phenotype that easily facilitates the development of IR, T2DM and in ammatory response, these animals are used in several experimental studies [11,12]. Due to paucity and the lack of standardization in studies evaluating the supplementation of prebiotics, probiotics and synbiotics in obesity, we proposed a study using an experimental model of leptin de cient obese mice (ob/ ob mice) to test the effects of synbiotic supplementation in this experimental model to evaluate the possible modulation of obesity, gut microbiota, gut integrity, and permeability.…”