Ventromedial hypothalamic lesions change the expression of cell proliferation-related genes and morphology-related genes in rat pancreatic islets

Abstract

Studies in normal rats and ob/ob mice indicated that islet neogenesis does not occur in the intact rodent pancreas. We previously reported that ventromedial hypothalamic (VMH) lesions stimulated cell proliferation of rat pancreatic islet B and acinar cells primarily through a cholinergic receptor mechanism and examined how gene families involved in cell proliferation in total pancreatic tissue are regulated after VMH lesions formation. This study examined how gene families involved in cell proliferation in pancreatic islets alone are regulated after VMH lesions formation. Pancreatic islet RNA was extracted, and differences in gene expression profiles between rats at day 3 after VMH lesioning and sham-VMH-lesioned rats were investigated using DNA microarray and real-time polymerase chain reaction. VMH lesions regulated genes that were involved in functions related to cell cycle and differentiation, growth, binding, apoptosis and morphology in pancreas islets. Real-time polymerase chain reaction also confirmed that gene expression of polo-like kinase 1 (Plk1) and topoisomerase (DNA) II a 170 kDa (Top2a), and stanniocalcin 1 (Stc1) were upregulated at day 3 after the VMH lesions. Ventromedial hypothalamic lesions may change the expression of cell proliferation-related genes and morphology-related genes in rat pancreatic islets.

Gene Expression Analysis in Rat Pancreas Observed with Whole-Transcript Exon Array after Ventromedial Hypothalamic Lesions

“…In comparison, in the Gene 1.0 ST array, the common categories in upregulated genes were immune (19%), metabolism (17%), and morphology (16%), and those in downregulated genes were metabolism (23%), immune (19%), differentiation (10%), and neuron (10%) ( Table 3 ). Consistent with this, we recently reported that using Gene 1.0 ST array in rat pancreatic islets rather than whole pancreatic tissues, VMH lesions affect the expressions of multiple cell proliferation, morphology, metabolism, and immune response genes [8][9][10] . Among the probes identified by these arrays, in downregulated genes, the same probes consisted of only 2 probes: L-threonine dehydrogenase and murinoglobulin 1, but in upregulated genes, the same probes were not found.…”

“…We recently described a technique that reliably improves the amount and quality of RNA extracted from rat pancreas, an RNaserich organ, using RNAlater-ICE [7] . DNA microarray was performed as described previously [8] . In this study, double-stranded complementary DNA was comprised of hybridized Affymetrix GeneChip arrays (Rat Gene 1.0 ST Array; Affymetrix Japan Co., Tokyo, Japan).…”

Identification and functional validation of human islet microRNAs associated with donor trait

“…A previous study had observed upregulation of Top2a in pancreatic islets in a model of ventromedial hypothalamic lesions [50]. NOX5 is a key mediator of human islet insulin secretion, however, in an over-nutrition-induced environment, NOX5 is involved in beta-cell damage [51].…”