Raile K, Klammt J, Garten A, Laue S, Blüher M, Kralisch S, Klöting N, Kiess W
Hospital for Children and Adolescents, Leipzig, Germany.
Regul Pept. 2006 Jul 15;135(1-2):30-8. doi: 10.1016/j.regpep.2006.03.004. Epub 2006 Apr 27.
The function and survival of pancreatic beta-cells strongly depend on glucose concentration and on autocrine secretion of peptide growth factors. NGF and its specific receptors TrkA and p75NTR play a pivotal role in islet survival and glucose-dependent insulin secretion. We therefore investigated whether or not glucose concentration influences expression of TrkA and p75NTR in rat islets and in INS-1E beta-cells at the mRNA and protein level (INS-1E).
Gene expression of the NGF receptors TrkA and p75NTR but also of the metabolic gene liver-type pyruvate kinase (L-PK) and the neurotrophin receptors TrkB and TrkC was studied by semi-quantitative PCR and by real-time PCR in islets and INS-1E beta-cells.
In rat islets, high glucose exposure (25 mmol/l) increased gene expression of TrkA, p75NTR and L-PK. Expression of TrkA, p75NTR and L-PK reflected insulin secretion at the respective glucose concentration. In rat INS-1E insulinoma cells, expression of L-PK and p75NTR was suppressed by low glucose as in the islets, while expression of TrkA was strongly increased by low glucose levels and thus was regulated differently than in islets. Expression of TrkB and TrkC was not regulated by glucose concentration at all. TrkA protein was regulated in the same fashion as its mRNA expression, while p75NTR protein was not significantly regulated within 24 h.
Glucose interacts with gene expression of TrkA and p75NTR that are strongly involved in beta-cell growth and glucose-dependent insulin secretion. The fact that TrkA expression is regulated the opposite way in islets and in INS-1E beta-cells might reflect their specific grade of differentiation and tendency to proliferate.
胰腺β细胞的功能和存活强烈依赖于葡萄糖浓度以及肽生长因子的自分泌。神经生长因子（NGF）及其特异性受体酪氨酸激酶A（TrkA）和p75神经营养因子受体（p75NTR）在胰岛存活和葡萄糖依赖性胰岛素分泌中起关键作用。因此，我们研究了葡萄糖浓度是否会在mRNA和蛋白质水平上影响大鼠胰岛及INS-1Eβ细胞（INS-1E）中TrkA和p75NTR的表达。
通过半定量PCR和实时PCR研究胰岛及INS-1Eβ细胞中NGF受体TrkA和p75NTR的基因表达，同时研究代谢基因肝型丙酮酸激酶（L-PK）以及神经营养因子受体酪氨酸激酶B（TrkB）和酪氨酸激酶C（TrkC）的基因表达。
在大鼠胰岛中，高糖暴露（25 mmol/l）可增加TrkA、p75NTR和L-PK的基因表达。TrkA、p75NTR和L-PK的表达反映了各自葡萄糖浓度下的胰岛素分泌情况。在大鼠INS-1E胰岛素瘤细胞中，与胰岛情况一样，低糖会抑制L-PK和p75NTR的表达，而低糖水平会强烈增加TrkA的表达，因此其调控方式与胰岛不同。TrkB和TrkC的表达根本不受葡萄糖浓度的调控。TrkA蛋白的调控方式与其mRNA表达相同，而p75NTR蛋白在24小时内未受到显著调控。
葡萄糖与TrkA和p75NTR的基因表达相互作用，而这二者在β细胞生长和葡萄糖依赖性胰岛素分泌中发挥重要作用。TrkA在胰岛和INS-1Eβ细胞中的表达调控方式相反，这一事实可能反映了它们不同的分化程度和增殖倾向。
