Effect of Hyperglycemia on Neuroligin - 2 mediated Insulin Secretion and In Silico Indentification of Small Molecule Activators of Neuroligin - 2

Abstract

Insulin, a peptide hormone, plays an important role in maintaining glucose homeostasis. It is produced and secreted by β cells. Diabetes mellitus has been characterized with hyperglycemia, and loss of Insulin in T1D, and in eventual stages of T2D. The decrease in Insulin is often associated with loss of β-cell mass. However, recent studies also show that the decrease in insulin levels are not only due to the loss of β cell mass, but also due to reduced insulin secretion in the alive β-cell mass. Insulin secretion occurs through exocytosis of LDCVs. β cells share a common linage with neurons, and thus also have a conserved mechanism of exocytosis consisting of docking, priming, and fusion, along with common proteins participating in the process. Neuroligin-2 is said to have an effect on the docking machinery recruitment. The present study aimed to assess effect of Hyperglycemia in Neuroligin-2 mediated Insulin secretion, in essence, figuring out how Neurolgiin-2 is affected in hyperglycemic conditions, and in turn does it affect the insulin secretion or not. This was done by assessing gene expression of the Neuroligin-2 in hyperglycemic conditions, and to assess its effect on insulin levels, upregulation and downregulation of Neuroligin was to be done, followed by assessment of insulin levels. However this phase of the study remained incomplete, and thus is inconclusive. Other than this, the study also aimed to find out viable candidates for therapeutic agents, which target Neuroligin-2. This was done by screening out candidate phytochemicals from various plants and through docking studies, interaction with neuroligin-2 was analyzed. This study found 11 candidates which may interact and affect Neuroligin-2 mediated insulin secretion.