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

• Published in: Endocrinology (Philadelphia) 1997-05, Vol.138 (5), p.1979-1987
• Main Authors: Meng, Yuan X, Wilson, Glenn W, Avery, Mary C, Varden, Crysti H, Balczon, Ron
• Format: Article
• Language: English
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/endo.138.5.5139

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 β-cell secretory activities, the role of kinesin in β-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 β-cells and transports the secretory granules from deep within the cytoplasm, where insulin is synthesized and processed, to the surface of β-cells upon secretory stimulation. To test this hypothesis, a mouse β-cell kinesin heavy chain complementary DNA was cloned and sequenced. Kinesin expression in primary cultures of mouse β-cells then was selectively suppressed by antimouse β-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 β-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.