Conditional glucagon receptor overexpression has multi-faceted consequences for beta-cell function

Background. Although it is known that the islet expression of glucagon receptors is increased in type 2 diabetes, its implication for beta-cell function is not known. Objective. To determine whether increased beta cell glucagon receptor expression and action influences multiple aspects of beta cell function. Materials/methods. Mice with beta cell specific overexpression of the glucagon receptor (RIP-Gcgr) were subjected to intravenous glucose tolerance tests with acute injections of glucagon or GLP-1. Mice were also subjected to intravenous arginine and carbachol tests and insulin secretory responses were evaluated. Results. The specific beta-cell overexpression of glucagon receptors has a complex and diverse consequence with dissociated consequences on beta-cell secretion depending on the stimulatory secretagogue in that whereas the potentiating effects of GLP-1 and arginine on glucose-stimulated insulin secretion were completely lost, the response to the muscarinic receptor agonist carbachol was largely unaffected and the insulin secretory response to glucose was exaggerated. Conclusion. This suggests that glucagon receptor overexpression, which is seen in hyperglycemia, may have dissociated consequence on beta cell function in its regulation under fasting, after meal and in response to autonomic nervous activation. (C) 2014 Elsevier Inc. All rights reserved.