Plotkin Balbina J, Halkyard Scott, Spoolstra Emily, Micklo Amanda, Kaminski Amber, Sigar Ira M, Konaklieva Monika I
Department of Microbiology and Immunology, Midwestern University, Downers Grove, IL 60515, USA.
Department of Chemistry, American University, Washington, DC 20016, USA.
Biology (Basel). 2023 Nov 15;12(11):1432. doi: 10.3390/biology12111432.
During the management of patients in acute trauma the resulting transient hyperglycemia is treated by administration of insulin. Since the effect of insulin, a quorum sensing compound, together with glucose affects biofilm formation in a concentration-specific manner, we hypothesize that the insulin/glucose ratio over the physiologic range modulates biofilm formation potentially influencing the establishment of infection through biofilm formation.
A variety of Gram-positive and Gram-negative bacteria were grown in peptone (1%) yeast nitrogen base broth overnight in 96-well plates with various concentrations of glucose and insulin. Biofilm formation was determined by the crystal violet staining procedure. Expression of insulin binding was determined by fluorescent microscopy (FITC-insulin). Controls were buffer alone, insulin alone, and glucose alone.
Overall, maximal biofilm levels were measured at 220 mg/dL of glucose, regardless of insulin concentration (10, 100, 200 µU/mL) of the organism tested. In general, insulin with glucose over the range of 160-180 mg/dL exhibited a pattern of biofilm suppression. However, either above or below this range, the presence of insulin in combination with glucose significantly modulated (increase or decrease) biofilm formation in a microbe-specific pattern. This modulation appears for some organisms to be reflective of the glucose-regulated intrinsic expression of bacterial insulin receptor expression.
Insulin at physiologic levels (normal and hyperinsulinemic) in combination with glucose can affect biofilm formation in a concentration-specific and microbe-specific manner. These findings may provide insight into the importance of co-regulation of the insulin/glucose ratio in patient management.
在急性创伤患者的治疗过程中，通过注射胰岛素来治疗由此产生的短暂高血糖症。由于胰岛素（一种群体感应化合物）与葡萄糖的共同作用会以浓度特异性方式影响生物膜形成，我们推测生理范围内的胰岛素/葡萄糖比值会调节生物膜形成，从而可能通过生物膜形成影响感染的发生。
将多种革兰氏阳性菌和革兰氏阴性菌在含有1%蛋白胨的酵母氮源肉汤中于96孔板中过夜培养，加入不同浓度的葡萄糖和胰岛素。通过结晶紫染色法测定生物膜形成情况。通过荧光显微镜（异硫氰酸荧光素标记的胰岛素）测定胰岛素结合的表达。对照组分别为单独的缓冲液、单独的胰岛素和单独的葡萄糖。
总体而言，无论所测试微生物的胰岛素浓度（10、100、200 μU/mL）如何，在葡萄糖浓度为220 mg/dL时测得最大生物膜水平。一般来说，葡萄糖浓度在160 - 180 mg/dL范围内时，胰岛素与葡萄糖共同作用表现出生物膜抑制模式。然而，在此范围之上或之下，胰岛素与葡萄糖共同存在会以微生物特异性模式显著调节（增加或减少）生物膜形成。对于某些微生物而言，这种调节似乎反映了细菌胰岛素受体表达的葡萄糖调节内在表达。
生理水平（正常和高胰岛素血症）的胰岛素与葡萄糖共同作用可通过浓度特异性和微生物特异性方式影响生物膜形成。这些发现可能有助于深入了解在患者治疗中共同调节胰岛素/葡萄糖比值的重要性。
