Korsgren Erik, Korsgren Olle
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Transplantation. 2016 Jan;100(1):111-5. doi: 10.1097/TP.0000000000000900.
Cure of diabetes and normalization of glucose disposal during intravenous glucose tolerance tests (IVGTT) remains critical for stringent evaluation of novel replacement therapies in type 1 diabetes. Glucose disposal during an IVGTT depends on a complex interaction of both insulin-dependent and -independent mechanisms. Glucose effectiveness, that is, the function of glucose per se, independent of insulin, to stimulate its uptake and suppress endogenous glucose production is less recognized.
To unravel the relative importance of these pathways, rats were injected with streptozotocin to induce diabetes and implanted subcutaneously with slow-release devices of insulin.
These animals demonstrated rapid normalization of blood glucose and perfectly normal glucose disposal during an IVGTT with no differences when compared with nondiabetic controls even though no active c-peptide secretion was detected in plasma and almost no remaining insulin-producing cells were present in the pancreas.
The present study highlights that glucose is the predominant mediator of its own disposal in rodents having only basal and nonglucose-regulated plasma insulin levels. The herein presented results calls for a reassessment how results obtained in the most commonly used experimental models should be interpreted in the development of future replacement therapies in type 1 diabetes.
在1型糖尿病新型替代疗法的严格评估中，糖尿病的治愈以及静脉葡萄糖耐量试验（IVGTT）期间葡萄糖代谢的正常化仍然至关重要。IVGTT期间的葡萄糖代谢取决于胰岛素依赖性和非胰岛素依赖性机制的复杂相互作用。葡萄糖自身效能，即葡萄糖本身独立于胰岛素刺激其摄取并抑制内源性葡萄糖生成的功能，尚未得到充分认识。
为了阐明这些途径的相对重要性，给大鼠注射链脲佐菌素以诱导糖尿病，并皮下植入胰岛素缓释装置。
这些动物在IVGTT期间血糖迅速恢复正常，葡萄糖代谢完全正常，与非糖尿病对照组相比无差异，尽管血浆中未检测到活性C肽分泌，且胰腺中几乎没有剩余的胰岛素产生细胞。
本研究强调，在仅具有基础和非葡萄糖调节血浆胰岛素水平的啮齿动物中，葡萄糖是其自身代谢的主要调节因子。本文呈现的结果呼吁重新评估在1型糖尿病未来替代疗法开发中如何解释最常用实验模型中获得的结果。
