Characterization of glucose sensing neuroendocrine cells

Abstract

Sensory cells located in the pancreas, the liver, the stomach and the intestines sense nutrient and peptide levels. A change in blood glucose concentration is one of the primary signals monitored by this cell type and alterations in the sensing capabilities of these glucose sensing cells may underlie the pathophysiology associated with obesity and diabetes. To understand how these glucose sensing cells function and what components are essential for maintaining glucose homeostatic mechanisms in the body, we characterized these cells by isolating and characterized the responses of these cells to glucose using functional assays. The principal glucose sensing cells of interest for our research were the neurons located within the hypothalamus, which are believed to integrate signals from sensory cells throughout the body to maintain energy homeostasis. We proposed that the mechanisms by which hypothalamic neurons sense glucose are similar to those used by pancreatic beta cells. By suggesting that hypothalamic neurons and pancreatic beta cells use similar mechanisms to sense and respond to changes in glucose levels, we hoped to identify the shared components to help us learn more about this unique and rare cell type. We found that the enzyme glucokinase (GK) was expressed throughout all stages of development along with the GLUT-1, GLUT-3 and GLUTX-1 glucose transporters, but that the liver form of GKRP was not found in the hypothalamus. The enzyme GK was also found in tissues of the distal stomach and proximal intestine of adult rats. Each of the 3 methods we employed, RT-PCR, in vitro functional assays and the development of a transgenic animal enabled us to initiate a line of research that may one day lead to a further understanding of how the body maintains energy homeostasis.