Insulinoma induces a hyperinsulinemia-mediated decrease of GLUT2 and GLP1 receptor in normal pancreatic ß-cells.

There have been several clinical reports of transient postoperative hyperglycemia in patients with insulinoma, but the effect of insulinoma on normal ß-cells has not been investigated. We examined the glucose transporter 2 (GLUT2) and glucagon-like peptide 1 receptor (GLP1R) expression in normal pancreatic ß-cells of five patients with insulinoma and five patients with normal glucose tolerance (NGT) as controls. The positive rate of GLUT2-or GLP1R-positive islets in the nontumor area was calculated by the ratio with the analyzed islets. For functional in vitro analyses, q-PCR and Western blotting were performed after insulin loading on MIN6 cells. The expression rates of both GLUT2 and GLP1R were significantly lower in nontumor area islets of insulinoma patients than in patients with NGT (GLUT2: 31.6 ± 15.3% vs 95.9 ± 6.7%, p < 0.01, GLP1R: 66.8 ± 15.0% vs 96.7 ± 5.0%, p < 0.01). Exposure of MIN6 cells to high concentrations of insulin resulted in a significant decrease in GLUT2 protein for 12 h and GLP1R protein for 24 h (GLUT2; 1.00 ± 0.079 vs 0.81 ± 0.04. p = 0.02, GLP1R; 1.00 ± 0.10 vs 0.50 ± 0.24, p = 0.03) but not in those mRNAs. Our findings show that insulinoma is associated with the downregulation of GLUT2 and GLP1R expression in nontumor area islets. These phenomena may be caused by high levels of insulin.

Influence of morphology and polymorphic transformation of fat crystals on the freeze-thaw stability of mayonnaise-type oil-in-water emulsions.

This study examined the destabilization of an oil-in-water (O/W) emulsion by freeze-thawing with a focus on the influence of the morphology and polymorph of fat crystals. For a model of food emulsion, this study used a mayonnaise-type O/W emulsion containing 70wt% canola oil (canola emulsion) or soybean oil (soybean emulsion) stored at -15, -20, and -30°C. The freeze-thaw stabilities of the emulsions were evaluated by measuring the upper oil layer after freeze-thawing. The soybean emulsion kept at -20°C had the highest stability; the other emulsions were destabilized during 6h of storage. Crystallization in the emulsions was determined using differential scanning calorimetry (DSC), time variation of temperature, X-ray diffraction measurement, and polarized light microscopy. DSC thermograms indicated that crystallization in emulsions occurred first in the high-melting fraction of oil, followed by water and, last, in the low-melting fraction of oil during cooling to -40°C. In the canola emulsion, the amount of fat crystals derived from the low-melting fraction of oil increased during storage at all temperatures, resulting in partial coalescence. The soybean emulsion was expected to be destabilized by polymorphic transformation (sub-α to ß' and ß) of fat crystals derived from the high-melting fraction during storage at -15 and -20°C. However, the soybean emulsion did not exhibit polymorphic transformation stored at -30°C, and the amount of fat crystals did not increase during freezing; thus, it was destabilized via a different mechanism.

Impairment of pupillary responses and optokinetic nystagmus in the mGluR6-deficient mouse.

Retinal bipolar cells receive glutamatergic transmission from photoreceptors and mediate a key process in segregating visual signals into ON-center and OFF-center pathways. The segregation of ON responses involves a G protein-coupled metabotropic glutamate receptor (mGluR). The mGluR6 subtype is expressed restrictedly at the postsynaptic site of retinal ON-bipolar cells. Ablation of mGluR6 in the ON-bipolar cells by gene targeting results in a loss of ON responses but unchanged OFF responses in visual transmission. Thus, mGluR6 is essential for inducing ON responses. The aims of this study are analyses of visual responsiveness and possible visual dysfunction in mGluR6-deficient mice. We report here that mGluR6-deficient mice have unaltered locomotor activity in a daily light-dark cycle and exhibit light-stimulated induction of Fos immunoreactivity in the suprachiasmatic nucleus. These findings indicate that mGluR6-deficient mice are capable or responding to light stimulation. The mGluR6 deficiency, however, markedly reduces the sensitivity of pupillary responses to light stimulus and severely impairs the ability to drive optokinetic nystagmus in response to visual contrasts. This study thus demonstrates that mGluR6 contributes to discrimination of visual contrasts.