Cruz-Cruz Iskra, Bernate-Obando Germán, Larqué Carlos, Escalona Rene, Pinto-Almazán Rodolfo, Velasco Myrian
Neuroscience Division, Department of Cognitive Neuroscience, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad Universitaria, AP 70-253 Coyoacán, México City 04510, Mexico.
Embriology and Genetics Deparment, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad Universitaria, AP 70-253 Coyoacán, México City 04510, Mexico.
Metabolites. 2022 Apr 18;12(4):365. doi: 10.3390/metabo12040365.
Metabolic syndrome (MS) is a cluster of metabolic signs that increases the risk of developing type 2 two diabetes mellitus and cardiovascular diseases. MS leads to pancreatic beta cell exhaustion and decreased insulin secretion through unknown mechanisms in a time-dependent manner. ATP-sensitive potassium channels (K channels), common targets of anti-diabetic drugs, participate in the glucose-stimulated insulin secretion, coupling the metabolic status and electrical activity of pancreatic beta cells. We investigated the early effects of MS on the conductance, ATP and glybenclamide sensitivity of the K channels. We used rats fed with a high-sucrose diet (HSD) for 8 weeks as a MS model. In excised membrane patches, control and HSD channels showed similar unitary conductance and ATP sensitivity pancreatic beta cells in their K channels In contrast, MS produced variability in the sensitivity to glybenclamide of K channels. We observed two subpopulations of pancreatic beta cells, one with similar (Gly1) and one with increased (Gly2) glybenclamide sensitivity compared to the control group. This study shows that the early effects of MS produced by consuming high-sugar beverages can affect the pharmacological properties of K channels to one of the drugs used for diabetes treatment.
代谢综合征(MS)是一组代谢体征,会增加患2型糖尿病和心血管疾病的风险。MS会导致胰腺β细胞耗竭,并通过未知机制以时间依赖性方式降低胰岛素分泌。ATP敏感性钾通道(K通道)是抗糖尿病药物的常见靶点,参与葡萄糖刺激的胰岛素分泌,将胰腺β细胞的代谢状态与电活动联系起来。我们研究了MS对K通道的电导、ATP和格列本脲敏感性的早期影响。我们将喂食高糖饮食(HSD)8周的大鼠用作MS模型。在切除的膜片中,对照和HSD通道在其K通道中显示出相似的单通道电导和ATP敏感性胰腺β细胞。相比之下,MS使K通道对格列本脲的敏感性产生了差异。我们观察到胰腺β细胞有两个亚群,与对照组相比,一个亚群对格列本脲的敏感性相似(Gly1),另一个亚群对格列本脲的敏感性增加(Gly2)。这项研究表明,饮用高糖饮料产生的MS早期影响可使K通道对一种糖尿病治疗药物的药理特性产生改变。