The Insulin Receptor Talks to Glucagon? Jesper Gromada, Alokesh Duttaroy, Patrik Rorsman  Cell Metabolism  Volume 9, Issue 4, Pages 303-305 (April 2009) DOI: 10.1016/j.cmet.2009.03.008 Copyright © 2009 Elsevier Inc. Terms and Conditions

Figure 1 Plasma Insulin, Glucagon, and Glucose Levels in Response to a Meal in Healthy Individual and Patients with T2DM Blood glucose levels are regulated by carefully orchestrated changes of insulin and glucagon secretion in response to carbohydrate meal ingestion in healthy individuals (Normal). An increased plasma glucose (left) following meal evokes insulin secretion from the β cells (middle); insulin secretion in individuals with T2DM is reduced (red-dotted line). Glucagon secretion is normally suppressed by the elevation of plasma glucose (right; blue line). In diabetic patients, the suppressor effect of glucose is reduced, and it may even stimulate glucagon release (right; red line). Data adapted from Dunning and Gerich (2007). Cell Metabolism 2009 9, 303-305DOI: (10.1016/j.cmet.2009.03.008) Copyright © 2009 Elsevier Inc. Terms and Conditions

Figure 2 Regulation of Glucagon by Insulin in Pancreatic α Cells In normal α cells, glucagon secretion is controlled by autocrine and paracrine processes (left). In addition, glucagon secretion is regulated by intrinsic α cell mechanisms (not shown). Increased glucose levels cause insulin release from β cell that activates α cell insulin receptor (IR). This activates PI3K/AKT pathway to open either KATP channels or recruitment of GABA-activated GABA receptor Cl− channels (GABA R; channels that are activated by GABA released from neighboring β cells). Both processes culminate in membrane hyperpolarization and inhibition of glucagon release. In patients with T2DM (middle), reduced insulin secretion leads to less activation of α cell insulin receptors and downstream processes will be correspondingly reduced, causing oversecretion of glucagon. In αIRKO islets (right) insulin signaling is abolished, and the relief from the paracrine suppression normally exerted via the insulin receptors account for stimulation of glucagon secretion. Cell Metabolism 2009 9, 303-305DOI: (10.1016/j.cmet.2009.03.008) Copyright © 2009 Elsevier Inc. Terms and Conditions