JCI - Altered function of insulin receptor substrate-1–deficient mouse islets and cultured β-cell lines

Altered function of insulin receptor substrate-1–deficient mouse islets and cultured β-cell lines

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

J Clin Invest. 1999; 104(12):R69–R75 doi:10.1172/JCI8339

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Figure 5

Reduced dose- and time-dependent glucose-stimulated insulin secretion in IRS-1–deficient islets. (a) Insulin secretion in response to glucose shows a dose-dependent decrease in insulin secretion in size-matched islets isolated from IRS-1^–/– and IRS-1^+/– mice compared with WT controls. Insulin secretion is expressed as a percent of the islet insulin content. Values are means ± SEM (n = 4–6). *P < 0.05 versus WT; ⁁P < 0.01 versus IRS-1^+/–. (b) Incubation of islets in the presence of 8.3 mM glucose showed a decreased insulin secretion in IRS-1^–/– and IRS-1^+/– islets compared with WT islets up to 60 minutes. Insulin secretion in IRS-1^–/– was lower even when compared with IRS-1^+/– islets at 30 and 60 minutes. Values are means ± SEM (n = 4–6). *P < 0.05 versus WT; ⁁P < 0.02 versus IRS-1^+/–; **P < 0.05 versus IRS-1^+/– or IRS-1^–/–. (c) Incubation of islets in 8.3 mM glucose showed a suppression of glucagon in all 3 groups. No significant differences in suppression could be observed between islets isolated from WT, IRS-1^–/–, and IRS-1^+/– mice. Values are means ± SEM (n = 4–6).