Cam M C, Li W M, McNeill J H
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Metabolism. 1997 Jul;46(7):769-78. doi: 10.1016/s0026-0495(97)90121-9.
Streptozotocin (STZ)-diabetic rats treated with vanadium can remain euglycemic for up to 20 weeks following withdrawal from vanadium treatment. In this study, we examined the effects of short-term vanadium treatment in preventing or reversing the STZ-induced diabetic state. Male Wistar rats were untreated (D) or treated (DT) with vanadyl sulfate for 1 week before administering STZ. Treatment was subsequently maintained for 3 days (DT3) or 14 days (DT14) post-STZ, after which vanadium was withdrawn. At 4 to 5 weeks post-STZ and following long-term withdrawal from vanadium, DT14 rats demonstrated levels of food and fluid intake and glucose tolerance that were not significantly different from those of age-matched untreated nondiabetic rats, and had significantly reduced glycemic levels in the fed state compared with D and DT3 groups. The proportion of animals that were euglycemic (fed plasma glucose < 9.0 mmol/L) was significant in DT14 (five of 10) relative to D (one of 10) and DT3 (one of 10) (P = .01). All euglycemic animals had an improved pancreatic insulin content that, albeit low (12% of control), was strongly linked to euglycemia in the fed state (r = -.91, P < .0001). Moreover, the highly significant correlation persisted with the analysis of untreated STZ-rats alone (r = -.95, P < .0001). Similarly, improvements in glucose tolerance and insulin secretory function in euglycemic rats were strongly correlated with small changes in residual insulin content. Hence, as vanadium pretreatment did not prevent STZ-induced beta-cytotoxicity, the vanadium-induced amelioration of the diabetic state appears to be secondary to the preservation of a functional portion of pancreatic beta cells that initially survived STZ toxicity. The partial preservation of pancreatic beta cells, albeit small in proportion to the total insulin store, was both critical and sufficient for a long-term reversal of the diabetic state. These results suggest that apparently modest effects in preserving residual pancreatic insulin content can have profound consequences on glucose homeostasis and may bear important implications for interventions that have "limited" protective effects on beta cells.
用链脲佐菌素（STZ）诱导糖尿病的大鼠在停止钒治疗后，血糖正常状态可维持长达20周。在本研究中，我们检测了短期钒治疗对预防或逆转STZ诱导的糖尿病状态的影响。雄性Wistar大鼠在给予STZ前未接受治疗（D组）或用硫酸氧钒治疗1周（DT组）。STZ注射后，治疗持续3天（DT3组）或14天（DT14组），之后停止钒治疗。在STZ注射后4至5周以及长期停止钒治疗后，DT14组大鼠的食物和液体摄入量及葡萄糖耐量水平与年龄匹配的未治疗非糖尿病大鼠无显著差异，且与D组和DT3组相比，进食状态下血糖水平显著降低。与D组（10只中的1只）和DT3组（10只中的1只）相比，DT14组（10只中的5只）血糖正常（进食时血浆葡萄糖<9.0 mmol/L）的动物比例显著更高（P = 0.01）。所有血糖正常的动物胰腺胰岛素含量均有所改善，尽管含量较低（为对照组的12%），但与进食状态下的血糖正常密切相关（r = -0.91，P < 0.0001）。此外，仅对未治疗的STZ诱导糖尿病大鼠进行分析时，这种高度显著的相关性依然存在（r = -0.95，P < 0.0001）。同样，血糖正常大鼠的葡萄糖耐量和胰岛素分泌功能改善与残余胰岛素含量的微小变化密切相关。因此，由于钒预处理未能预防STZ诱导的β细胞毒性，钒诱导的糖尿病状态改善似乎继发于胰腺β细胞功能部分的保留，这些β细胞最初在STZ毒性中存活下来。胰腺β细胞的部分保留，尽管与总胰岛素储备相比比例较小，但对于糖尿病状态的长期逆转至关重要且足够。这些结果表明，在保留残余胰腺胰岛素含量方面看似适度的作用可能对葡萄糖稳态产生深远影响，并且可能对那些对β细胞具有“有限”保护作用的干预措施具有重要意义。
