Hyperglycemia in rodent models of type 2 diabetes requires insulin-resistant alpha cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 111; no. 36; pp. 13217 - 13222
• Main Authors: Lee, Young, Berglund, Eric D., Yu, Xinxin, Wang, May-Yun, Evans, Matthew R., Scherer, Philipp E., Holland, William L., Charron, Maureen J., Roth, Michael G., Unger, Roger H.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 09-09-2014; National Acad Sciences
• Subjects: Alpha cells; Animals; Beta cells; Biological Sciences; Blood Glucose - metabolism; Body Temperature - drug effects; Body Weight - drug effects; Cell Line; Ceramides - pharmacology; Cricetinae; Diabetes; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - pathology; Diet; Disease Models, Animal; Feeding Behavior - drug effects; Genetics; Glucagon - metabolism; Glucagon-Secreting Cells - drug effects; Glucagon-Secreting Cells - metabolism; Glucagon-Secreting Cells - pathology; Hyperglycemia; Hyperglycemia - blood; Hyperglycemia - complications; Hyperglycemia - pathology; Hyperinsulinism; Hyperinsulinism - blood; Hyperinsulinism - complications; Hyperinsulinism - pathology; Insulin; Insulin - blood; Insulin - genetics; Insulin - pharmacology; Insulin resistance; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - pathology; Lipogenesis - drug effects; Liver; Male; Mice, Inbred C57BL; Obesity; Proteins; Rats; Receptors, Glucagon - metabolism; RNA, Messenger - blood; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Type 1 diabetes mellitus; Type 2 diabetes mellitus; type two diabetes; insulin resistance
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1409638111

Significance Diet-induced type 2 diabetes (T2D) is becoming a worldwide epidemic. Patients with T2D fail to respond to insulin normally and have elevated blood glucose and insulin. In autoimmune diabetes, blood glucose is elevated due to uncontrolled glucagon, a hormone normally suppressed and opposed by insulin. To study the role of glucagon in T2D, rodent models of the disease were created lacking glucagon action. These animals failed to develop hyperglycemia unless glucagon action was restored or the animals were given the high concentrations of insulin typical of animals with T2D. This indicates that the unopposed glucagon action in T2D is necessary to support elevated blood glucose of diabetes. Suppressing glucagon or its action may benefit patients with T2D.