Abdel-Halim S M, Guenifi A, Luthman H, Grill V, Efendic S, Ostenson C G
Department of Endocrinology, Karolinska Hospital and Institute, Stockholm, Sweden.
Diabetes. 1994 Feb;43(2):281-8. doi: 10.2337/diab.43.2.281.
The impact of genetic factors and maternal diabetes on glucose tolerance and pancreatic beta-cell function was studied in first generation (F1) offspring generated in crosses between the spontaneously diabetic Goto-Kakizaki (GK)-Wistar rat and normoglycemic control Wistar rats (W). The (GK x W) F1 hybrids were offspring of either male GK (mGK) and female Wistar (fW) (mGK x fW) or male Wistar (mW) and female GK (fGK) (mW x fGK) rats. Already at 8 days of age, blood glucose levels were elevated in GK (7.6 +/- 0.5 vs. 4.8 +/- 0.3 mM in W; P < 0.001) and in F1 rats (6.0 +/- 0.3 in mGK x fW and 6.6 +/- 0.4 mM in mW x fGK; both P < 0.01 vs. W). In 2-month-old male rats, glucose (2 g/kg, intraperitoneally) markedly increased blood glucose levels after 60 min in GK rats (18.1 +/- 0.6 vs. 5.5 +/- 0.3 mM in W; P < 0.001) and moderately increased levels in F1 rats (9.9 +/- 0.9 in mGK x fW and 11.6 +/- 1.0 mM in mW x fGK, both P < 0.01 vs. W). Similar patterns were obtained in female rats. Repeated backcrossing of F1 with W rats successively improved glucose tolerance. In perfused pancreases of male rats, the 20-min insulin response to 16.7 mM glucose was -7.44 +/- 5.18 pmol in GK rats, 71.57 +/- 12.25 pmol in W rats, 9.00 +/- 0.89 pmol in mGK x fW rats, and 18.20 +/- 3.97 pmol in mW x fGK rats.(ABSTRACT TRUNCATED AT 250 WORDS)
在自发性糖尿病的Goto-Kakizaki(GK)-Wistar大鼠与正常血糖的对照Wistar大鼠(W)杂交产生的第一代(F1)后代中,研究了遗传因素和母体糖尿病对葡萄糖耐量和胰腺β细胞功能的影响。(GK×W)F1杂种是雄性GK(mGK)和雌性Wistar(fW)(mGK×fW)或雄性Wistar(mW)和雌性GK(fGK)(mW×fGK)大鼠的后代。在8日龄时,GK大鼠(7.6±0.5 vs. W大鼠的4.8±0.3 mM;P<0.001)和F1大鼠(mGK×fW中为6.0±0.3,mW×fGK中为6.6±0.4 mM;两者与W相比P<0.01)的血糖水平就已升高。在2月龄雄性大鼠中,葡萄糖(2 g/kg,腹腔注射)使GK大鼠60分钟后的血糖水平显著升高(18.1±0.6 vs. W大鼠的5.5±0.3 mM;P<0.001),使F1大鼠的血糖水平适度升高(mGK×fW中为9.9±0.9,mW×fGK中为11.6±1.0 mM,两者与W相比P<0.01)。在雌性大鼠中也获得了类似的模式。F1与W大鼠反复回交可逐渐改善葡萄糖耐量。在雄性大鼠的灌注胰腺中,对16.7 mM葡萄糖的20分钟胰岛素反应在GK大鼠中为-7.44±5.18 pmol,在W大鼠中为71.57±12.25 pmol,在mGK×fW大鼠中为9.00±0.89 pmol,在mW×fGK大鼠中为18.20±3.97 pmol。(摘要截断于250字)