Long-term inhibition of protein tyrosine kinase impairs electrophysiologic activity and a rapid component of exocytosis in pancreatic beta cells

Zhao, Yu-Feng, Keating, Damien J, Hernandez, Maria, Feng, Dan Dan, Zhu, Yulong and Chen, Chen (2005) Long-term inhibition of protein tyrosine kinase impairs electrophysiologic activity and a rapid component of exocytosis in pancreatic beta cells. Journal of Molecular Endocrinology, 35 1: 49-59. doi:10.1677/jme.1.01779


Author Zhao, Yu-Feng
Keating, Damien J
Hernandez, Maria
Feng, Dan Dan
Zhu, Yulong
Chen, Chen
Title Long-term inhibition of protein tyrosine kinase impairs electrophysiologic activity and a rapid component of exocytosis in pancreatic beta cells
Journal name Journal of Molecular Endocrinology   Check publisher's open access policy
ISSN 1479-6813
0952-5041
Publication date 2005
Year available 2005
Sub-type Article (original research)
DOI 10.1677/jme.1.01779
Volume 35
Issue 1
Start page 49
End page 59
Total pages 11
Place of publication Bristol, England
Publisher Society for Endocrinology
Collection year 2005
Language eng
Subject 110306 Endocrinology
110201 Cardiology (incl. Cardiovascular Diseases)
111201 Cancer Cell Biology
Abstract Dysfunction of pancreatic -cells is a fundamental feature in the pathogenesis of type 2 diabetes. As insulin receptor signaling occurs via protein tyrosine kinase (PTK), we investigated the role of PTK activity in the etiology of -cell dysfunction by inhibiting PTK activity in primary cultured mouse pancreatic -cells and INS-1 cells with genistein treatment over 24 h. Electrophysiologic recordings showed genistein treatment significantly attenuated ATP-sensitive K+ (KATP) and voltage-dependent Ca2+ currents, and depolarized the resting membrane potential in primary -cells. When stimulated by high glucose, genistein-treated -cells exhibited a time delay of both depolarization and Ca2+ influx, and were unable to fire action potentials, as well as displaying a reduced level of Ca2+ influx and a loss of Ca2+ oscillations. Semiquantitative PCR analysis revealed decreased expression of KATP and L-type Ca2+ channel mRNA in genistein-treated islets. PTK inhibition also significantly reduced the rapid component of secretory vesicle exocytosis, as indicated by membrane capacitance measurements, and this is likely to be due to the reduced Ca2+ current amplitude in these cells. These results illustrate that compromised PTK activity contributes to pancreatic -cell dysfunction and may be involved in the etiology of type 2 diabetes.
References Akiyama T, Ishida J, Nakagawa S, Ogawara H, Watanabe S, Itoh N, Shibuya M & Fukami Y 1987 Genistein, a specific inhibitor of tyrosine-specific protein kinases. Journal of Biological Chemistry 262 5592–5595. Ammon HP, Reiber C & Verspohl EJ 1991 Indirect evidence for short-loop negative feedback of insulin secretion in the rat. Journal of Endocrinology 128 27–34. Ashcroft FM & Rorsman P 1989 Electrophysiology of the pancreatic -cell. Progress in Biophysics and Molecular Biology 54 87–143. Ashcroft FM & Rorsman P 2004 Molecular defects in insulin secretion in type-2 diabetes. Reviews in Endocrine and Metabolic Disorders 5 135–142. Ashcroft SJ 2000 The -cell KATP channel. Journal of Membrane Biology 176 187–206. Aspinwall CA, Qian WJ, Roper MG, Kulkarni RN, Kahn CR & Kennedy RT 2000 Roles of insulin receptor substrate-1, phosphatidylinositol 3-kinase, and release of intracellular Ca2+ stores in insulin-stimulated insulin secretion in -cells. Journal of Biological Chemistry 275 22331–22338. Bokvist K, Eliasson L, Ammala C, Renstrom E & Rorsman P 1995 Co-localization of L-type Ca2+ channels and insulin-containing secretory granules and its significance for the initiation of exocytosis in mouse pancreatic -cells. EMBO Journal 14 50–57. Borge PD, Moibi J, Greene SR, Trucco M, Young RA, Gao Z & Wolf BA 2002 Insulin receptor signaling and sarco/endoplasmic reticulum calcium ATPase in -cells. Diabetes 51 S427-S433. de Souza CJ, Capotorto JV, Cornell-Kennon S, Wu YJ, Steil GM, Trivedi N & Weir GC 2000 -cell dysfunction in 48-hour glucose-infused rats is not a consequence of elevated plasma lipid or islet triglyceride levels. Metabolism 49 755–759. Easom RA 2000 -granule transport and exocytosis. Seminars in Cell and Developmental Biology 11 253–266. Elahi D, Nagulesparan M, Hershcopf RJ, Muller DC, Tobin JD, Blix PM, Rubenstein AH, Unger RH & Andres R 1982 Feedback inhibition of insulin secretion by insulin: relation to the hyperinsulinemia of obesity. New England Journal of Medicine 306 1196–1202. Gilon P, Yakel J, Gromada J, Zhu Y, Henquin JC & Rorsman P 1997 G protein-dependent inhibition of L-type Ca2+ currents by acetylcholine in mouse pancreatic -cells. Journal of Physiology 499 65–76. Gopel S, Kanno T, Barg S, Galvanovskis J & Rorsman P 1999 Voltage-gated and resting membrane currents recorded from -cells in intact mouse pancreatic islets. Journal of Physiology 521 717–728. Gu Y, Preston MR, Magnay J, El Haj AJ & Publicover SJ 2001 Hormonally-regulated expression of voltage-operated Ca2+ channels in osteocytic (MLO-Y4) cells. Biochemical and Biophysical Research Communications 282 536–542. Jacqueminet S, Briaud I, Rouault C, Reach G & Poitout V 2000 Inhibition of insulin gene expression by long-term exposure of pancreatic -cells to palmitate is dependent on the presence of a stimulatory glucose concentration. Metabolism 49 532–536. Jonas JC, Plant TD, Gilon P, Detimary P, Nenquin M & Henquin JC 1995 Multiple effects and stimulation of insulin secretion by the tyrosine kinase inhibitor genistein in normal mouse islets. British Journal of Pharmacology 114 872–880. Jonas JC, Sharma A, Hasenkamp W, Ilkova H, Patane G, Laybutt R, Bonner-Weir S & Weir GC 1999 Chronic hyperglycemia triggers loss of pancreatic cell differentiation in an animal model of diabetes. Journal of Biological Chemistry 274 14112–14121. Josefsen K, Stenvang JP, Kindmark H, Berggren PO, Horn T, Kjaer T & Buschard K 1996 Fluorescence-activated cell sorted rat islet cells and studies of the insulin secretory process. Journal of Endocrinology 149 145–154. Kanno T, Ma X, Barg S, Eliasson L, Galvanovskis J, Gopel S, Larsson M, Renstrom E & Rorsman P 2004 Large dense-core vesicle exocytosis in pancreatic -cells monitored by capacitance measurements. Methods 33 302–311. Kulkarni RN, Bruning JC, Winnay JN, Postic C, Magnuson MA & Kahn CR 1999a Tissue-specific knockout of the insulin receptor in pancreatic cells creates an insulin secretory defect similar to that in type 2 diabetes. Cell 96 329–339. Kulkarni RN, Winnay JN, Daniels M, Bruning JC, Flier SN, Hanahan D & Kahn CR 1999b Altered function of insulin receptor substrate-1-deficient mouse islets and cultured -cell lines. Journal of Clinical Investigation 104 R69-R75. Kulkarni RN, Holzenberger M, Shih DQ, Ozcan U, Stoffel M, Magnuson MA & Kahn CR 2002 -cell-specific deletion of the Igf1 receptor leads to hyperinsulinemia and glucose intolerance but does not alter -cell mass. Nature Genetics 31 111–115. Larsson O, Kindmark H, Brandstrom R, Fredholm B & Berggren PO 1996 Oscillations in KATP channel activity promote oscillations in cytoplasmic free Ca2+ concentration in the pancreatic cell. PNAS 93 5161–5165. Leibiger B, Leibiger IB, Moede T, Kemper S, Kulkarni RN, Kahn CR, de Vargas LM & Berggren PO 2001 Selective insulin signaling through A and B insulin receptors regulates transcription of insulin and glucokinase genes in pancreatic cells. Molecular Cell 7 559–570. 58 Y-F ZHAO and others · Impairment of -cell function by genistein Journal of Molecular Endocrinology (2005) 35, 49–59 www.endocrinology-journals.org Liu M & Shapiro ME 1995 A new method for isolation of murine islets with markedly improved yields. Transplant Proceedings 27 3208–3210. Matthews DR 2001 Insulin resistance and -cell function – a clinical perspective. Diabetes, Obesity and Metabolism 3 S28-S33. Mears D 2004 Regulation of insulin secretion in islets of Langerhans by Ca2+ channels. Journal of Membrane Biology 200 57–66. Merglen A, Theander S, Rubi B, Chaffard G, Wollheim CB & Maechler P 2004 Glucose sensitivity and metabolism-secretion coupling studied during two-year continuous culture in INS-1E insulinoma cells. Endocrinology 145 667–678. Nie GY, Li Y, Minoura H, Findlay JK & Salamonsen LA 2003 Specific and transient up-regulation of proprotein convertase 6 at the site of embryo implantation and identification of a unique transcript in mouse uterus during early pregnancy. Biology of Reproduction 68 439–447. Plant TD 1988 Properties and calcium-dependent inactivation of calcium currents in cultured mouse pancreatic -cells. Journal of Physiology 404 731–747. Poitout V & Robertson RP 2002 Minireview: secondary -cell failure in type 2 diabetes – a convergence of glucotoxicity and lipotoxicity. Endocrinology 143 339–342. Prentki M, Tornheim K & Corkey BE 1997 Signal transduction mechanisms in nutrient-induced insulin secretion. Diabetologia 40 S32-S41. Rhodes CJ & White MF 2002 Molecular insights into insulin action and secretion. European Journal of Clinical Investigation 32 S3-S13. Rolland JF, Henquin JC & Gilon P 2002 Feedback control of the ATP-sensitive K+ current by cytosolic Ca2+ contributes to oscillations of the membrane potential in pancreatic -cells. Diabetes 51 376–384. Roper MG, Qian WJ, Zhang BB, Kulkarni RN, Kahn CR & Kennedy RT 2002 Effect of the insulin mimetic L-783,281 on intracellular Ca2+ and insulin secretion from pancreatic -cells. Diabetes 51 S43-S49. Rorsman P 1997 The pancreatic -cell as a fuel sensor: an electrophysiologist’s viewpoint. Diabetologia 40 487–495. Schulla V, Renstrom E, Feil R, Feil S, Franklin I, Gjinovci A, Jing XJ, Laux D, Lundquist I, Magnuson MA, Obermuller S, Olofsson CS, Salehi A, Wendt A, Klugbauer N, Wollheim CB, Rorsman P & Hofmann F 2003 Impaired insulin secretion and glucose tolerance in cell-selective Cav1·2 Ca2+ channel null mice. EMBO Journal 22 3844–3854. Tokuyama Y, Sturis J, DePaoli AM, Takeda J, Stoffel M, Tang J, Sun X, Polonsky KS & Bell GI 1995 Evolution of -cell dysfunction in the male Zucker diabetic fatty rat. Diabetes 44 1447–1457. van Haeften TW 2002 Early disturbances in insulin secretion in the development of type 2 diabetes mellitus. Molecular and Cellular Endocrinology 197 197–204. Weyer C, Bogardus C, Mott DM & Pratley RE 1999 The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. Journal of Clinical Investigation 104 787–794. Wiser O, Trus M, Hernandez A, Renstrom E, Barg S, Rorsman P & Atlas D 1999 The voltage sensitive Lc-type Ca2+ channel is functionally coupled to the exocytotic machinery. PNAS 96 248–253.
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Biomedical Sciences Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 6 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 13 Jan 2009, 13:10:27 EST by Marianne Steentsma on behalf of School of Biomedical Sciences