Vanderbilt University School of Medicine

Jacobson, David Aaron , Ph.D.
Assistant Professor of Molecular Physiology and Biophysics

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Phone Number: 615-875-7655


Jacobson, David's picture

Office Address   Mailing Address

7425B MRB IV


Research Keywords
Islet, Action potential, Calcium channels, Potassium channels, Phosphorylation, Sumoylation,Diabetes,Ion transport,Physiology

Research Specialty
Secretagogue induced mechanisms regulating pancreatic islet electrical activity and hormone secretion

Research Description
Maintaining physiological blood glucose levels is a complex process critically dependent on insulin secretion. Glucose stimulation of pancreatic beta-cells results in orchestrated electrical signaling that triggers insulin secretion. Our interest is in understanding how beta-cell ion channels are regulated during glucose stimulation and how these mechanisms become perturbed in diabetes.

Research on secretagogue modulation of beta-cell ion channels has primarily focused on the ATP sensitive potassium channel, KATP, which is an essential ion channel for normal glucose stimulated insulin secretion (GSIS). However, rodents with nonfunctional KATP channels and diabetic patients treated with blockers to KATP still exhibit glucose regulated insulin secretion. Thus KATP independent glucose responsive mechanisms play an important role during GSIS in humans. The mechanism(s) for this is unknown; however, as calcium is required for insulin secretion the mechanism must in part be coupled to calcium influx. Therefore, we are investigating the ion channels and their molecular mechanisms of regulation, independent of KATP, that help modulate secretagogue induced calcium influx and insulin secretion. The focus of this research is primarily on voltage-dependent calcium channels (CaV) and leak potassium channels. This research will test hypotheses concerning glucose and G-protein dependent regulation of islet electrical activity by CaV channel phosphorylation and modulation of islet membrane potential by leak potassium channels. These studies utilize molecular biology, genetics, fluorescent microscopy, and electrophysiology techniques on pancreatic islet-cells. Understanding how secretagogues regulate islet electrical activity distinctly from KATP may help to develop new therapies for diabetic patients that target specific elements of the beta-cell excitation-secretion pathway.

Dadi, PK, Luo, B, Vierra, NC, Jacobson, DA. TASK-1 Potassium Channels Limit Pancreatic ??-Cell Calcium Influx and Glucagon Secretion. Mol Endocrinol, 29(5), 777-87, 2015.

Golson, ML, Dunn, JC, Maulis, MF, Dadi, PK, Osipovich, AB, Magnuson, MA, Jacobson, DA, Gannon, M. Activation of FoxM1 revitalizes the replicative potential of aged ?? -cells in male mice and enhances insulin secretion. Diabetes, , , 2015.

Vierra, NC, Dadi, PK, Jeong, I, Dickerson, M, Powell, DR, Jacobson, DA. The type-2 diabetes-associated K+ channel TALK-1 modulates beta-cell electrical excitability, 2nd-phase insulin secretion, and glucose homeostasis. Diabetes, , , 2015.

Dadi, PK, Vierra, NC, Jacobson, DA. Pancreatic beta-cell specific ablation of TASK-1 channels augments glucose-stimulated calcium entry and insulin secretion, improving glucose tolerance. Endocrinology, , en20132051, 2014.

Dadi, PK, Vierra, NC, Ustione, A, Piston, DW, Colbran, RJ, Jacobson, DA. Inhibition of Pancreatic Beta-Cell Ca2+/Calmodulin-dependent Protein Kinase II Reduces Glucose-stimulated Calcium Influx and Insulin Secretion, Impairing Glucose Tolerance. J Biol Chem, 289(18), 12435-45, 2014.

Egnatchik, RA, Leamy, AK, Jacobson, DA, Shiota, M, Young, JD. ER calcium release promotes mitochondrial dysfunction and hepatic cell lipotoxicity in response to palmitate overload. Mol Metab, 3(5), 544-53, 2014.

Raphemot, R, Swale, DR, Dadi, PK, Jacobson, DA, Cooper, P, Wojtovich, AP, Banerjee, S, Nichols, CG, Denton, JS. Direct Activation of Beta-Cell KATP Channels with a Novel Xanthine Derivative. Mol Pharmacol, 85(6), 858-65, 2014.

Baerenwald, DA, Bonnefond, A, Bouatia-Naji, N, Flemming, BP, Umunakwe, OC, Oeser, JK, Pound, LD, Conley, NL, Cauchi, S, Lobbens, S, Eury, E, Balkau, B, Lantieri, O, , , Dadi, PK, Jacobson, DA, Froguel, P, O''Brien, RM. Multiple functional polymorphisms in the G6PC2 gene contribute to the association with higher fasting plasma glucose levels. Diabetologia, 56(6), 1306-16, 2013.

Fridlyand, LE, Jacobson, DA, Philipson, LH. Ion channels and regulation of insulin secretion in human beta-cells: a computational systems analysis. Islets, 5(1), 1-15, 2013.

Kaihara, KA, Dickson, LM, Jacobson, DA, Tamarina, N, Roe, MW, Philipson, LH, Wicksteed, B. Beta-Cell-specific protein kinase A activation enhances the efficiency of glucose control by increasing acute-phase insulin secretion. Diabetes, 62(5), 1527-36, 2013.

Pound, LD, Oeser, JK, O''Brien, TP, Wang, Y, Faulman, CJ, Dadi, PK, Jacobson, DA, Hutton, JC, McGuinness, OP, Shiota, M, O''Brien, RM. G6PC2: a negative regulator of basal glucose-stimulated insulin secretion. Diabetes, 62(5), 1547-56, 2013.

Denton, JS, Jacobson, DA. Channeling dysglycemia: ion-channel variations perturbing glucose homeostasis. Trends Endocrinol Metab, 23(1), 41-8, 2012.

Pound, LD, Sarkar, SA, Ustione, A, Dadi, PK, Shadoan, MK, Lee, CE, Walters, JA, Shiota, M, McGuinness, OP, Jacobson, DA, Piston, DW, Hutton, JC, Powell, DR, O''Brien, RM. The physiological effects of deleting the mouse SLC30A8 gene encoding zinc transporter-8 are influenced by gender and genetic background. PLoS One, 7(7), e40972, 2012.

Jacobson, DA, Mendez, F, Thompson, M, Torres, J, Cochet, O, Philipson, LH. Calcium-activated and voltage-gated potassium channels of the pancreatic islet impart distinct and complementary roles during secretagogue induced electrical responses. J Physiol, , , 2010.

Deriy, LV, Gomez, EA, Jacobson, DA, Wang, X, Hopson, JA, Liu, XY, Zhang, G, Bindokas, VP, Philipson, LH, Nelson, DJ. The granular chloride channel ClC-3 is permissive for insulin secretion. Cell Metab, 10(4), 316-23, 2009.

Fridlyand, LE, Jacobson, DA, Kuznetsov, A, Philipson, LH. A model of action potentials and fast Ca2+ dynamics in pancreatic beta-cells. Biophys J, 96(8), 3126-39, 2009. PMCID:2718303

Jacobson, DA, Wicksteed, BL, Philipson, LH. The alpha-cell conundrum: ATP-sensitive K+ channels and glucose sensing. Diabetes, 58(2), 304-6, 2009. PMCID:2628601

Bao, S, Jacobson, DA, Wohltmann, M, Bohrer, A, Jin, W, Philipson, LH, Turk, J. Glucose homeostasis, insulin secretion, and islet phospholipids in mice that overexpress iPLA2beta in pancreatic beta-cells and in iPLA2beta-null mice. Am J Physiol Endocrinol Metab, 294(2), E217-29, 2008. PMCID:2268609

David A. Jacobson and Louis H. Philipson. Ion Channels and Insulin secretion. Pancreatic Beta Cells in Health and Disease, , 91-110, 2008.

Jacobson, DA, Kuznetsov, A, Lopez, JP, Kash, S, Amm??l??, CE, Philipson, LH. Kv2.1 ablation alters glucose-induced islet electrical activity, enhancing insulin secretion. Cell Metab, 6(3), 229-35, 2007. PMCID:2699758

Jacobson, DA, Philipson, LH. TRP channels of the pancreatic beta cell. Handb Exp Pharmacol, (179), 409-24, 2007. PMCID:2699758

Jacobson, DA, Philipson, LH. Action potentials and insulin secretion: new insights into the role of Kv channels. Diabetes Obes Metab, 9 Suppl 2, 89-98, 2007. PMCID:2628601

Jacobson, DA, Weber, CR, Bao, S, Turk, J, Philipson, LH. Modulation of the pancreatic islet beta-cell-delayed rectifier potassium channel Kv2.1 by the polyunsaturated fatty acid arachidonate. J Biol Chem, 282(10), 7442-9, 2007. PMCID:2044499

Jacobson, DA, Cho, J, Landa, LR, Tamarina, NA, Roe, MW, Buxbaum, JD, Philipson, LH. Downstream regulatory element antagonistic modulator regulates islet prodynorphin expression. Am J Physiol Endocrinol Metab, 291(3), E587-95, 2006. PMCID:2044499

Postdoctoral Position Available

Postdoctoral Position Details
Positions in islet biology and electrophysiology are currently available.

Updated Date

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