Muscarinic control of MIN6 pancreatic β cells is enhanced by impaired amino acid signaling.
We have shown recently that the class C G protein-coupled receptor T1R1/T1R3 taste receptor complex is an early amino acid sensor in MIN6 pancreatic β cells. Amino acids are unable to activate ERK1/2 in β cells in which T1R3 has been depleted. The muscarinic receptor agonist carbachol activated ERK1/2 better in T1R3-depleted cells than in control cells. Ligands that activate certain G protein-coupled receptors in pancreatic β cells potentiate glucose-stimulated insulin secretion. Among these is the M3 muscarinic acetylcholine receptor, the major muscarinic receptor in β cells. We found that expression of M3 receptors increased in T1R3-depleted MIN6 cells and that calcium responses were altered. To determine whether these changes were related to impaired amino acid signaling, we compared responses in cells exposed to reduced amino acid concentrations. M3 receptor expression was increased, and some, but not all, changes in calcium signaling were mimicked. These findings suggest that M3 acetylcholine receptors are increased in β cells as a mechanism to compensate for amino acid deficiency.
From the Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9041.
Marcy L
ML
Guerra
From the Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9041.
Eric M
EM
Wauson
From the Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9041.
Kathleen
K
McGlynn
From the Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9041 Melanie.Cobb@UTSouthwestern.edu.
Melanie H
MH
Cobb
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D043587:Receptor, Muscarinic M3 / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D000596:Amino Acids; D043587:Receptor, Muscarinic M3; D043562:Receptors, G-Protein-Coupled; C431926:taste receptors, type 1; D002217:Carbachol; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D002118:Calcium
Calcium; Diabetes; ERK; G Protein-coupled Receptors (GPCR); mTOR Complex (mTORC)