1. ¹Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
2. ²Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN, USA
3. ³VA Tennessee Valley Healthcare System, Nashville, TN, USA

Correspondence: Dr AC Powers, Division of Diabetes, Endocrinology, and Metabolism, 715 PRB, Vanderbilt University, Nashville, TN 37232, USA. E-mail: Al.Powers@vanderbilt.edu

Received 17 September 2002; Accepted 17 February 2003.

Abstract

Glucagon-like peptide 1 (GLP-1) is released from neuroendocrine cells in the intestine in the postprandial state and augments glucose-stimulated insulin secretion from pancreatic cells. To develop non- cells that exhibit physiologically regulated insulin secretion, we coexpressed the GLP-1 receptor and human insulin in primary rat pituitary cells using adenovirus-mediated gene transfer. The transduced cells were analyzed in a perifusion system and after transplantation into mice. Normal pituitary cells do not express the GLP-1 receptor as shown by the absence of GLP-1 receptor mRNA and the inability of GLP-1 to stimulate pituitary hormone secretion. Following transduction with an adenovirus carrying the GLP-1 receptor cDNA, the pituitary cells expressed functional GLP-1 receptors as reflected by the ability of GLP-1 to stimulate secretion of pituitary hormones. When both the GLP-1 receptor and human insulin were introduced, GLP-1 stimulated cosecretion of human insulin and endogenous pituitary hormones. GLP-1 was similar in potency to the hypothalamic-releasing hormones and stimulated hormone secretion in a dose-dependent fashion. In contrast to pancreatic cells, the hormone-releasing effect of GLP-1 on transduced pituitary cells was not dependent on the concentration of extracellular glucose. After transplantation of pituitary cells coexpressing human insulin and GLP-1 receptor into mice, enteral glucose stimulated insulin secretion. These results demonstrate a new approach to engineer physiologically regulated insulin secretion by non- cells.