Pharmacology, Toxicology and Clinical Pharmacy


Possible New Strategies for the Treatment of Congenital Hyperinsulinism

Jelena Sikimic, Theresa Hoffmeister, Anne Gresch, Julia Kaiser, Winfried Barthlen, Carmen Wolke, Ilse Wieland, Uwe Lendeckel, Peter Krippeit-Drews, Martina Düfer and Gisela Drews

Front. Endocrinol., 27 October 2020 |

Acyl-Ghrelin Influences Pancreatic β-Cell Function by Interference with KATP Channels.

Kaiser J, Krippeit-Drews P, Drews G.

Diabetes. 2020 Nov 5:db200231. doi: 10.2337/db20-0231.

Approved LXR agonists exert unspecific effects on pancreatic β-cell function.

Maczewsky J, Kaiser J, Krippeit-Drews P, Drews G.

Endocrine. 2020 Jun;68(3):526-535. doi: 10.1007/s12020-020-02241-4. Epub 2020 Mar 7. 

ATP-binding without hydrolysis switches sulfonylurea receptor 1 (SUR1) to outward-facing conformations that activate KATP channels.

Sikimic J, McMillen TS, Bleile C, Dastvan F, Quast U, Krippeit-Drews P, Drews G, Bryan J.

J Biol Chem. 2018 Dec 26. pii: jbc.RA118.005236. doi: 10.1074/jbc.RA118.005236. [Epub ahead of print]

TGR5 Activation Promotes Stimulus-Secretion Coupling of Pancreatic Beta-Cells via a PKA-Dependent Pathway.

Maczewsky J, Kaiser J, Gresch A, Gerst F, Düfer M, Krippeit-Drews P, Drews G.

Diabetes. 2018 Nov 8. pii: db180315. doi: 10.2337/db18-0315. [Epub ahead of print]

ATP mediates a negative autocrine signal on stimulus-secretion coupling in mouse pancreatic β-cells.

Bauer C, Kaiser J, Sikimic J, Krippeit-Drews P, Düfer M, Drews G.

Endocrine. 2018 Sep 18. doi: 10.1007/s12020-018-1731-0. [Epub ahead of print]

Energy depletion and not ROS formation is a crucial step of glucolipotoxicity (GLTx) in pancreatic beta cells.
Barroso Oquendo M, Layer N, Wagner R, Krippeit-Drews P, Drews G.
Pflugers Arch. 2018, 470:537-547.

Atrial Natriuretic Peptide Affects Stimulus-Secretion Coupling of Pancreatic β-Cells.
Undank S, Kaiser J, Sikimic J, Düfer M, Krippeit-Drews P, Drews G.
Diabetes. 2017, 66:2840-2848.

The LXR Ligand T0901317 Acutely Inhibits Insulin Secretion by Affecting Mitochondrial Metabolism.
Maczewsky J, Sikimic J, Bauer C, Krippeit-Drews P, Wolke C, Lendeckel U, Barthlen W, Drews G.
Endocrinology. 2017, 158:2145-2154.

The Angiotensin-(1-7)/Mas Axis Improves Pancreatic β-Cell Function in Vitro and in Vivo.
Sahr A, Wolke C, Maczewsky J, Krippeit-DrewsP, Tetzner A, Drews G, Venz S, Gürtler S, van den Brandt J, Berg S, Döring P, Dombrowski F, Walther T, Lendeckel U.
Endocrinology. 2016 157:4677-4690.

Evidence against a Ca2+-induced potentiation of dehydrogenase activity in pancreatic beta-cells.
Drews G, Bauer C, Edalat A, Düfer M, Krippeit-Drews P.
Pflügers Arch. 2015 467:2389-2397.

Mitochondrial succinate dehydrogenase is involved in stimulus-secretion coupling and endogenous ROS formation in murine beta cells.
Edalat A, Schulte-Mecklenbeck P, Bauer C, Undank S, Krippeit-Drews P, Drews G, Düfer M.
Diabetologia. 2015 58:1532-1541.

Human Islets Exhibit Electrical Activity on Microelectrode Arrays (MEA).
Schönecker S, Kraushaar U, Guenther E, Gerst F, Ullrich S, Häring HU, Königsrainer A, Barthlen W, Drews G, Krippeit-Drews P.
Exp Clin Endocrinol Diabetes. 2015 123:296-298.

Role of FXR in β-cells of lean and obese mice.
Schittenhelm B, Wagner R, Kähny V, Peter A, Krippeit-Drews P, Düfer M, Drews G.
Endocrinology. 2015 156:1263-1271.

Long-term culture and functionality of pancreatic islets monitored using microelectrode arrays.
Schönecker S, Kraushaar U, Düfer M, Sahr A, Härdtner C, Guenther E, Walther R, Lendeckel U, Barthlen W, Krippeit-Drews P, Drews G.
"Integrative biology: quantitative biosciences from nano to macro" Integr Biol (Camb). 2014 6:540-544.

Glitazones exert multiple effects on β-cell stimulus-secretion coupling.
Düfer M, Noack K, Edalat A, Krippeit-Drews P, Drews G.
"Molecular pharmacology"Mol Pharmacol. 2013 83:51-60.

The significance of the nuclear farnesoid X receptor (FXR) in β cell function.
Düfer M, Hörth K, Krippeit-Drews P, Drews G.
"Islets" Islets. 2012 4:333-338. Review.

H₂O₂ lowers the cytosolic Ca²⁺ concentration via activation of cGMP-dependent protein kinase Iα.
Müller PM, Gnügge R, Dhayade S, Thunemann M, Krippeit-Drews P, Drews G, Feil R.
"Free radical biology & medicine"Free Radic Biol Med. 2012 53:1574-1583.

Role of K(ATP) channels in β-cell resistance to oxidative stress.
Drews G, Düfer M.
"Diabetes, obesity & metabolism" Diabetes Obes Metab, 2012 Suppl 3:120-128

Bile acids acutely stimulate insulin secretion of mouse β-cells via farnesoid X receptor activation and K(ATP) channel inhibition.
Düfer M, Hörth K, Wagner R, Schittenhelm B, Prowald S, Wagner TF, Oberwinkler J, Lukowski R, Gonzalez FJ, Krippeit-Drews P, Drews G.
"Diabetes" Diabetes. 2012 61:1479-1489

Rapid functional evaluation of beta-cells by extracellular recording of membrane potential oscillations with microelectrode arrays.
Pfeiffer T, Kraushaar U, Düfer M, Schönecker S, Haspel D, Günther E, Drews G, Krippeit-Drews
"Pflugers Archiv: European journal of physiology" Pflügers Arch - EJP. 2011 462:835-840.

Activation of the AMP-activated protein kinase enhances glucose-stimulated insulin secretion in mouse β-cells.
Düfer M, Noack K, Krippeit-Drews P, Drews G.
"Islets" Islets. 2010 2:156-63.

BK channels affect glucose homeostasis and cell viability of murine pancreatic beta cells.
Düfer M, Neye Y, Hörth K, Krippeit-Drews P, Hennige A, Widmer H, McClafferty H, Shipston MJ, Häring HU, Ruth P, Drews G.
Diabetologia. 2011 54:423-432

Oxidative stress and beta-cell dysfunction.
Drews G, Krippeit-Drews P, Düfer M.
Pflügers Arch -EJP. 2010 Jul 23. [Epub ahead of print]

The Gq/G11-mediated signaling pathway is critical for autocrine potentiation of insulin secretion in mice.
Sassmann A, Gier B, Gröne HJ, Drews G, Offermanns S, Wettschureck N.
J Clin Invest. 2010 May 3. pii: 41541. doi: 10.1172/JCI41541. [Epub ahead of print]

Activation of the AMP-activated protein kinase enhances glucose-stimulated insulin secretion in mouse beta-cell
Martina Düfer, Katja Noack, Peter Krippeit-Drews and Gisela Drews
Islets 2010;2:1-9

Overexpression of kinase-negative protein kinase Cdelta in pancreatic beta-cells protects mice from diet-induced glucose intolerance and beta-cell dysfunction.
Hennige AM, Ranta F, Heinzelmann I, Düfer M, Michael D, Braumüller H, Lutz SZ, Lammers R, Drews G, Bosch F, Häring HU, Ullrich S.
Diabetes. 2010;59:119-127

Electrophysiology of islet cells.
Drews G, Krippeit-Drews P, Düfer M.
"Advances in experimental medicine and biology"Adv Exp Med Biol. 2010;654:115-63

Suppression of KATP channel activity protects murine pancreatic beta cells against oxidative stress.
Gier B, Krippeit-Drews P, Sheiko T, Aguilar-Bryan L, Bryan J, Düfer M, Drews G.
"The Journal of clinical investigation" J Clin Invest. 2009;119:3246-3256

Enhanced glucose tolerance by SK4 channel inhibition in pancreatic beta-cells.
Düfer M, Gier B, Wolpers D, Krippeit-Drews P, Ruth P, Drews G.
"Diabetes" Diabetes. 2009;58:1835-1843.

Activation of the Na+/K+-ATPase by insulin and glucose as a putative negative feedback mechanism in pancreatic beta-cells.
Düfer M, Haspel D, Krippeit-Drews P, Aguilar-Bryan L, Bryan J, Drews G.
"Pflugers Archiv: European journal of physiology" Pflugers Arch. 2009;457:1351-1360.

Regulation of calcineurin activity in insulin-secreting cells: stimulation by Hsp90 during glucocorticoid-induced apoptosis.
Ranta F, Düfer M, Stork B, Wesselborg S, Drews G, Häring HU, Lang F, Ullrich S.
Cell Signal. 2008;20:1780-1786

An adenylate kinase is involved in KATP channel regulation of mouse pancreatic beta cells.
Schulze DU, Düfer M, Wieringa B, Krippeit-Drews P, Drews G.
"Diabetologia"Diabetologia. 2007;50:2126-2134.

The KATP channel is critical for calcium sequestration into non-ER compartments in mouse pancreatic beta cells.
Dufer M, Haspel D, Krippeit-Drews P, Kelm M, Ranta F, Nitschke R, Ullrich S, Aguilar-Bryan L, Bryan J, Drews G.
"Cellular physiology and biochemistry: international journal of experimental cellular physiology, biochemistry, and pharmacology" Cell Physiol Biochem. 2007;20:65-74.

Resveratrol binds to the sulfonylurea receptor (SUR) and induces apoptosis in a SUR subtype-specific manner.
Hambrock A, de Oliveira Franz CB, Hiller S, Grenz A, Ackermann S, Schulze DU, Drews G, Osswald H.
J Biol Chem. 2007;282:3347-3356

ABCC8 and ABCC9: ABC transporters that regulate K+ channels.
Bryan J, Muñoz A, Zhang X, Düfer M, Drews G, Krippeit-Drews P, Aguilar-Bryan L.
"Pflugers Archiv: European journal of physiology" Pflügers Arch. 2007 Feb;453:703-718.

HIV protease inhibitors: suppression of insulin secretion by inhibition of voltage-dependent K+ currents and anion currents.
Neye Y, Düfer M, Drews G, Krippeit-Drews P.
"The Journal of pharmacology and experimental therapeutics" J Pharmacol Exp Ther. 2006;316:106-112.

Dexamethasone induces cell death in insulin-secreting cells, an effect reversed by exendin-4.
Ranta F, Avram D, Berchtold S, Düfer M, Drews G, Lang F, Ullrich S.
Diabetes. 2006;55:1380-1390

Crosstalk between membrane potential and cytosolic Ca2+ concentration in beta cells from Sur1-/- mice.
Haspel D, Krippeit-Drews P, Aguilar-Bryan L, Bryan J, Drews G, Düfer M.
"Diabetologia" Diabetologia. 2005;48:913-921.

Direct interference of HIV protease inhibitors with pancreatic beta-cell function.
Düfer M, Neye Y, Krippeit-Drews P, Drews G.
"Naunyn-Schmiedeberg's archives of pharmacology" Naunyn Schmiedebergs Arch Pharmacol. 2004;369:583-590.

Oscillations of membrane potential and cytosolic Ca2+ concentration in SUR1-/- beta cells.
Düfer M, Haspel D, Krippeit-Drews P, Aguilar-Bryan L, Bryan J, Drews G.
"Diabetologia" Diabetologia. 2004;47:488-498.

Palmitate-induced Ca2+-signaling in pancreatic beta-cells.
Remizov O, Jakubov R, Düfer M, Krippeit Drews P, Drews G, Waring M, Brabant G, Wienbergen A, Rustenbeck I, Schöfl C.
"Molecular and cellular endocrinology" Mol Cell Endocrinol. 2003;212:1-9

Phosphocreatine as a determinant of KATP channel activity in pancreatic beta-cells.
Krippeit-Drews P, Bäcker M, Düfer M, Drews G.
"Pflugers Archiv: European journal of physiology" Pflügers Arch. 200 ;445:556-562.

Methyl pyruvate stimulates pancreatic beta-cells by a direct effect on KATP channels, and not as a mitochondrial substrate.
Düfer M, Krippeit-Drews P, Buntinas L, Siemen D, Drews G.
"The Biochemical journal" Biochem J. 2002;368:817-825.

Inhibition of mitochondrial function affects cellular Ca2+ handling in pancreatic B-cells.
Düfer M, Krippeit-Drews P, Drews G.
"Pflugers Archiv: European journal of physiology" Pflügers Arch. 2002;444:236-243.

Diabetogenic effect of cyclosporin A is mediated by interference with mitochondrial function of pancreatic B-cells.
Düfer M, Krippeit-Drews P, Lembert N, Idahl LA, Drews G.
"Molecular pharmacology" Mol Pharmacol. 2001;60:873-879

Stimulation of leukotriene synthesis in intact polymorphonuclear cells by the 5-lipoxygenase inhibitor 3-oxo-tirucallic acid.
Boden SE, Schweizer S, Bertsche T, Düfer M, Drews G, Safayhi H.
Mol Pharmacol. 2001;60:267-273

Contrasting effects of alloxan on islets and single mouse pancreatic beta-cells.
Drews G, Krämer C, Düfer M, Krippeit-Drews P.
Biochem J. 2000;352:389-397

Dual effect of NO on KATP current of mouse pancreatic B-cells: stimulation by deenergizing mitochondria and inhibition by direct interaction with the channel.
Drews G, Krämer C, Krippeit-Drews P.
"Biochimica et biophysica acta" Biochim Biophys Acta. 2000;1464:62-68

Parallel oscillations of intracellular calcium activity and mitochondrial membrane potential in mouse pancreatic B-cells.
Krippeit-Drews P, Düfer M, Drews G.
Biochem Biophys Res Commun. 2000;267:179-183

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