Cell Metab：VGF的C端肽段TLQP-21或可治疗二型糖尿病

7月3日，国际知名期刊Cell Metabolism发表了美国杜克大学研究人员的成果，VGF衍生的一个肽段TLQP-21可以缓解二型糖尿病的发展，它主要通过增强胰岛β细胞的存活和功能发挥作用。

胰岛β细胞功能的退化是二型糖尿病发展的最后一步。研究人员发现，在大鼠胰岛中过表达转录因子Nkx6.1有双重作用，即葡萄糖刺激的胰岛素分泌增加（GSIS，glucose-stimulated insulin secretion），胰岛β细胞复制增加。

进一步的研究发现，Nkx6.1可显著地提高大鼠胰岛中的激素原VGF的表达量，而TLQP-21是VGF的C端肽段。在大鼠和人的胰岛中， TLQP-21都可增强GSIS，提高葡萄糖耐受。在前驱糖尿病的大鼠胰岛中慢性注射TLQP-21可保护胰岛细胞和缓解糖尿病的发生。

随后的体外实验发现，TLQP-21与GLP-1R激动剂的作用机制方面有很多类似之处，如增强GSIS、增强血糖控制、减少胰岛细胞凋亡，但无抑制胃排空和增加心率的功能。因此，TLQP-21或许可以用于治疗二型糖尿病。

doi:10.1016/j.cmet.2012.05.011
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Diabetes via Enhancement of Islet β-Cell Survival and Function

Samuel B. Stephens1, 2, Jonathan C. Schisler1, 5, Hans E. Hohmeier1, 3, Jie An1, Albert Y. Sun4, Geoffrey S. Pitt2, 4, Christopher B. Newgard1

Deterioration of functional islet β-cell mass is the final step in progression to Type 2 diabetes. We previously reported that overexpression of Nkx6.1 in rat islets has the dual effects of enhancing glucose-stimulated insulin secretion (GSIS) and increasing β-cell replication. Here we show that Nkx6.1 strongly upregulates the prohormone VGF in rat islets and that VGF is both necessary and sufficient for Nkx6.1-mediated enhancement of GSIS. Moreover, the VGF-derived peptide TLQP-21 potentiates GSIS in rat and human islets and improves glucose tolerance in vivo. Chronic injection of TLQP-21 in prediabetic ZDF rats preserves islet mass and slows diabetes onset. TLQP-21 prevents islet cell apoptosis by a pathway similar to that used by GLP-1, but independent of the GLP-1, GIP, or VIP receptors. Unlike GLP-1, TLQP-21 does not inhibit gastric emptying or increase heart rate. We conclude that TLQP-21 is a targeted agent for enhancing islet β-cell survival and function.