Dept. of Anatomy, Cellular Biology, Physiology and Biophysics, Institute of Biology, State University of Campinas, Campinas, Brazil.
Am J Physiol Regul Integr Comp Physiol. 2010 Feb;298(2):R320-8. doi: 10.1152/ajpregu.00256.2009. Epub 2009 Nov 11.
Insulin resistance during pregnancy is counteracted by enhanced insulin secretion. This condition is aggravated by obesity, which increases the risk of gestational diabetes. Therefore, pancreatic islet functionality was investigated in control nonpregnant (C) and pregnant (CP), and cafeteria diet-fed nonpregnant (Caf), and pregnant (CafP) obese rats. Isolated islets were used for measurements of insulin secretion (RIA), NAD(P)H production (MTS), glucose oxidation ((14)CO(2) production), intracellular Ca(2+) levels (fura-2 AM), and gene expression (real-time PCR). Impaired glucose tolerance was clearly established in Caf and CafP rats at the 14th wk on a diet. Insulin secretion induced by direct depolarizing agents such as KCl and tolbutamide and increasing concentrations of glucose was significantly reduced in Caf, compared with C islets. This reduction was not observed in islets from CP and CafP rats. Accordingly, the glucose oxidation and production of reduced equivalents were increased in CafP islets. The glucose-induced Ca(2+) increase was significantly lower in Caf and higher in CafP, compared with all other groups. CP and CafP islets demonstrated an increased Ca(2+) oscillation frequency, compared with both C and Caf islets, and the amplitude of oscillations was augmented in CafP, compared with Caf islets. In addition, Ca(v)alpha1.2 and SERCA2a mRNA levels were reduced in Caf islets. Ca(v)alpha1.2, but not SERCA2a, mRNA was normalized in CafP islets. In conclusion, cafeteria diet-induced obesity impairs insulin secretion. This alteration is related to the impairment of Ca(2+) handling in pancreatic islets, in especial Ca(2+) influx, a defect that is reversed during pregnancy allowing normalization of insulin secretion.
胰岛素抵抗在怀孕期间会被增强的胰岛素分泌所抵消。肥胖会加重这种情况，增加妊娠糖尿病的风险。因此，研究了对照组非妊娠（C）和妊娠（CP）、 cafeteria 饮食喂养非妊娠（Caf）和妊娠（CafP）肥胖大鼠的胰岛功能。分离的胰岛用于胰岛素分泌（RIA）、NAD（P）H 产生（MTS）、葡萄糖氧化（（14）CO（2）产生）、细胞内 Ca（2+）水平（fura-2 AM）和基因表达（实时 PCR）的测量。在节食第 14 周时，Caf 和 CafP 大鼠明显出现糖耐量受损。与 C 胰岛相比，KCl 和甲苯磺丁脲等直接去极化剂和葡萄糖浓度增加诱导的胰岛素分泌明显减少。在 CP 和 CafP 大鼠的胰岛中未观察到这种减少。因此，CafP 胰岛的葡萄糖氧化和还原当量产生增加。与所有其他组相比，Caf 和 CafP 胰岛的葡萄糖诱导的 Ca（2+）增加显著降低。与 C 和 Caf 胰岛相比，CP 和 CafP 胰岛的 Ca（2+）振荡频率增加，与 Caf 胰岛相比，CafP 胰岛的振荡幅度增加。此外，Caf 胰岛的 Ca（v）alpha1.2 和 SERCA2a mRNA 水平降低。与 Caf 胰岛相比，CafP 胰岛的 Ca（v）alpha1.2，但不是 SERCA2a，mRNA 水平正常化。总之， cafeteria 饮食诱导的肥胖会损害胰岛素分泌。这种改变与胰岛 Ca（2+）处理的损害有关，特别是 Ca（2+）内流，这一缺陷在怀孕期间得到纠正，允许胰岛素分泌正常化。
