| First Author | Fraenkel M | Year | 2006 |
| Journal | J Endocrinol | Volume | 189 |
| Issue | 3 | Pages | 519-28 |
| PubMed ID | 16731783 | Mgi Jnum | J:109083 |
| Mgi Id | MGI:3625680 | Doi | 10.1677/joe.1.06656 |
| Citation | Fraenkel M, et al. (2006) Sex-steroid milieu determines diabetes rescue in pttg-null mice. J Endocrinol 189(3):519-28 |
| abstractText | Male mice that are pttg-null develop sexually dimorphic diabetes with hypoinsulinemia secondary to reduced post-natal -cell proliferation and an inability to expand islet cell mass with aging. We therefore examined the effects of sex-steroid manipulation on diabetes development in pttg(-/-) male mice. Surgical gonadectomy was followed by implantation of 90-day slow-release pellets releasing 17beta-estradiol (0.36 mg/pellet), placebo or dihydrotestosterone (DHT; 12.5 mg/pellet). Mean fasting blood sugars at the end of the study were 414 +/- 54 mg/dl for pttg(-/-) controls and 371 +/- 14 mg/dl for pttg(-/-) mice gonad-ectomized and treated with DHT compared with 124 +/- 40 and 85 +/- 12 mg/dl in gonadectomized pttg(-/-) males treated with placebo or estradiol, respectively (P < 0.01 compared with control pttg(-/-)). Gonadectomy with and without estradiol treatment did not increase the very low circulating insulin levels in pttg-null males (fasting insulin 0.44 +/- 0.04 ng/ml in pttg(-/-) controls, 0.47 +/- 0.07 and 0.4 ng/ml in pttg(-/-) gonadectomized males treated with placebo or estradiol, respectively). Gonadectomy increased serum adiponectin levels (4.9 +/- 008 mug/ml in pttg(-/-) controls versus 13 +/- 0.08 and 7.5 +/- 0.6 mug/ml in pttg(-/-) gonadectomized males treated with placebo or estradiol, respectively; P < 0.001 and P < 0.05), accompanied by increased insulin sensitivity. The results show that gonadectomy delayed, and gonadectomy with additional estradiol treatment prevented, diabetes development in pttg(-/-) males, possibly through increased insulin sensitivity mediated by elevated serum adiponectin levels. Male-selective effects of disrupted beta-cell proliferation in the absence of pttg are restored by sex-steroid effects on peripheral insulin sensitivity. |
