Dysregulation of glucose homeostasis in PICK1-deficient mice.

<p>(A) Impaired glucose tolerance in PICK1-deficient mice. OGTT was done in 10–13-wk-old WT (+/+) and PICK1-deficient mice (−/−) after overnight fast. White circles, PICK1 +/+; black circles, PICK1 −/−. The inset shows area under curve (AUC). Data are means ± SE (<i>n</i> = 9). **<i>p</i><0.01. (B) Mice deficient in PICK1 display decreased insulin secretion during OGTT. White bars, PICK1 +/+: black bars, PICK1 −/−. Data are means ± SE. *<i>p</i><0.05. (C) Mice deficient in PICK1 (27–29 wk) display preserved or even improved insulin sensitivity in the ITT. White circles, PICK1 +/+; black circles, PICK1 −/−. Data are means ± SE (<i>n</i> = 9–11). AUC was significantly lower for the PICK1-deficient mice compared to WT mice. *<i>p</i><0.05. (D) The protein expression level of the insulin receptor as determined by quantification of Western blots on liver samples from 35–38-wk-old mice after overnight fasting was significantly increased in PICK1-deficient mice (−/−) compared to WT (+/+) mice (means ± SE, *<i>p</i> = 0.024). Western blots with insulin receptor and actin immunoreactivity of two representative samples out of 13 PICK−/− and 10 PICK+/+ samples are shown below. (E) The plasma levels of triglycerides (TG) after overnight fasting were significantly decreased in PICK1-deficient mice (−/−) compared to WT (+/+) mice (154±15 versus 103±9, <i>n</i> = 10–13, **<i>p</i> = 0.0056).