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Altered function of insulin receptor substrate-1–deficient mouse islets and cultured β-cell lines
Rohit N. Kulkarni, … , Douglas Hanahan, C. Ronald Kahn
Rohit N. Kulkarni, … , Douglas Hanahan, C. Ronald Kahn
Published December 15, 1999
Citation Information: J Clin Invest. 1999;104(12):R69-R75. https://doi.org/10.1172/JCI8339.
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Altered function of insulin receptor substrate-1–deficient mouse islets and cultured β-cell lines

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Abstract

Insulin receptor substrate–1 (IRS-1) is pivotal in mediating the actions of insulin and growth factors in most tissues of the body, but its role in insulin-producing β islet cells is unclear. Freshly isolated islets from IRS-1 knockout mice and SV40-transformed IRS-1–deficient β-cell lines exhibit marked insulin secretory defects in response to glucose and arginine. Furthermore, insulin expression is reduced by about 2-fold in the IRS-1–null islets and β-cell lines, and this defect can be partially restored by transfecting the cells with IRS-1. These data provide evidence for an important role of IRS-1 in islet function and provide a novel functional link between the insulin signaling and insulin secretion pathways.

Authors

Rohit N. Kulkarni, Jonathon N. Winnay, Molly Daniels, Jens C. Brüning, Sarah N. Flier, Douglas Hanahan, C. Ronald Kahn

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Figure 3

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Islet morphology and electron microscopy. (a) Sections of pancreas were ...
Islet morphology and electron microscopy. (a) Sections of pancreas were stained for non–β cells using a cocktail antibody as described in Methods. Representative sections of pancreas from WT and IRS-1–/– mice show an approximately 2-fold increase in islet size in the latter. (b) Representative section of pancreas from an IRS-1–/– mouse stained for insulin as described in Methods shows insulin staining of β cells in the islets. Spotty insulin staining can be observed throughout the exocrine pancreas, indicating the presence of insulin-containing cells. (c) Electron microscopic examination of β cells in islets from IRS-1–/– mice was performed as described. A scant electron dense granulation pattern was observed in IRS-1–/– β cells compared with WT cells. An increased number of autophagic vacuoles (arrows) were observed in individual IRS-1–/– β cells. A representative photograph is shown. ×9,690.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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