This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Meng, Y. X. Articles by Balczon, R. Search for Related Content PubMed PubMed Citation Articles by Meng, Y. X. Articles by Balczon, R.

Suppression of the Expression of a Pancreatic ß-Cell Form of the Kinesin Heavy Chain by Antisense Oligonucleotides Inhibits Insulin Secretion from Primary Cultures of Mouse ß-Cells¹

Department of Structural and Cellular Biology, University of South Alabama, Mobile, Alabama 36688

Address all correspondence and requests for reprints to: Dr. Ron Balczon, Department of Structural and Cellular Biology, University of South Alabama, Mobile, Alabama 36688.

Granular/vesicular transport is thought to be supported by microtubule-based force-generating adenosine triphosphatases such as kinesin. Kinesin is a motor molecule that has been well studied in brain and other neuronal tissues. Although vesicular transport is important for pancreatic ß-cell secretory activities, the role of kinesin in ß-cell function has not been investigated. It is hypothesized that kinesin functions as a translocator that associates with both microtubules and insulin-containing granules in ß-cells and transports the secretory granules from deep within the cytoplasm, where insulin is synthesized and processed, to the surface of ß-cells upon secretory stimulation. To test this hypothesis, a mouse ß-cell kinesin heavy chain complementary DNA was cloned and sequenced. Kinesin expression in primary cultures of mouse ß-cells then was selectively suppressed by antimouse ß-cell kinesin heavy chain antisense oligonucleotide treatment. Analysis of insulin secretion determined that the basal level of insulin secretion from the treated cells was decreased by 50%. Furthermore, glucose-stimulated insulin release from treated ß-cells was reduced by almost 70% after suppression of kinesin expression by antisense treatment. The findings from this study provide the first direct evidence that kinesin, a microtubule-based motor protein, plays an important role in insulin secretion.

This article has been cited by other articles:

				A. S. Narang and R. I. Mahato Biological and biomaterial approaches for improved islet transplantation. Pharmacol. Rev., June 1, 2006; 58(2): 194 - 243. [Abstract] [Full Text] [PDF]

				Y. Uchizono, M. Iwase, U. Nakamura, N. Sasaki, D. Goto, and M. Iida Tacrolimus Impairment of Insulin Secretion in Isolated Rat Islets Occurs at Multiple Distal Sites in Stimulus-Secretion Coupling Endocrinology, May 1, 2004; 145(5): 2264 - 2272. [Abstract] [Full Text] [PDF]

				A. K. Nevins and D. C. Thurmond Glucose regulates the cortical actin network through modulation of Cdc42 cycling to stimulate insulin secretion Am J Physiol Cell Physiol, September 1, 2003; 285(3): C698 - C710. [Abstract] [Full Text] [PDF]

				C.-H. Xia, E. A. Roberts, L.-S. Her, X. Liu, D. S. Williams, D. W. Cleveland, and L. S.B. Goldstein Abnormal neurofilament transport caused by targeted disruption of neuronal kinesin heavy chain KIF5A J. Cell Biol., April 14, 2003; 161(1): 55 - 66. [Abstract] [Full Text] [PDF]

				M. E. Doyle and J. M. Egan Pharmacological Agents That Directly Modulate Insulin Secretion Pharmacol. Rev., March 1, 2003; 55(1): 105 - 131. [Abstract] [Full Text] [PDF]

				M. J. Donelan, G. Morfini, R. Julyan, S. Sommers, L. Hays, H. Kajio, I. Briaud, R. A. Easom, J. D. Molkentin, S. T. Brady, et al. Ca2+-dependent Dephosphorylation of Kinesin Heavy Chain on beta -Granules in Pancreatic beta -Cells. IMPLICATIONS FOR REGULATED beta -GRANULE TRANSPORT AND INSULIN EXOCYTOSIS J. Biol. Chem., June 28, 2002; 277(27): 24232 - 24242. [Abstract] [Full Text] [PDF]

				A. Varadi, E. K. Ainscow, V. J. Allan, and G. A. Rutter Involvement of conventional kinesin in glucose-stimulated secretory granule movements and exocytosis in clonal pancreatic {beta}-cells J. Cell Sci., January 11, 2002; 115(21): 4177 - 4189. [Abstract] [Full Text] [PDF]

				Q Li, D Hansen, A Killilea, H. Joshi, R. Palazzo, and R Balczon Kendrin/pericentrin-B, a centrosome protein with homology to pericentrin that complexes with PCM-1 J. Cell Sci., January 2, 2001; 114(4): 797 - 809. [Abstract] [PDF]

				E. Bertelli, M. Regoli, F. Gambelli, M. Lucattelli, G. Lungarella, and A. Bastianini GFAP Is Expressed as a Major Soluble Pool Associated with Glucagon Secretory Granules in A-cells of Mouse Pancreas J. Histochem. Cytochem., September 1, 2000; 48(9): 1233 - 1242. [Abstract] [Full Text]

				Y. Kanai, Y. Okada, Y. Tanaka, A. Harada, S. Terada, and N. Hirokawa KIF5C, a Novel Neuronal Kinesin Enriched in Motor Neurons J. Neurosci., September 1, 2000; 20(17): 6374 - 6384. [Abstract] [Full Text] [PDF]