Expression of insulin receptor (IR) A and B isoforms, IGF-IR, and IR/IGF-IR hybrid receptors in vascular smooth muscle cells and their role in cell migration in atherosclerosis.

BACKGROUND: Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) is a major contributor to the development of atherosclerotic process. In a previous work, we demonstrated that the insulin receptor isoform A (IRA) and its association with the insulin-like growth factor-I receptor (IGF-IR) confer a proliferative advantage to VSMCs. However, the role of IR and IGF-IR in VSMC migration remains poorly understood. METHODS: Wound healing assays were performed in VSMCs bearing IR (IRLoxP+/+ VSMCs), or not (IR-/- VSMCs), expressing IRA (IRA VSMCs) or expressing IRB (IRB VSMCs). To study the role of IR isoforms and IGF-IR in experimental atherosclerosis, we used ApoE-/- mice at 8, 12, 18 and 24 weeks of age. Finally, we analyzed the mRNA expression of total IR, IRB isoform, IGF-IR and IGFs by qRT-PCR in the medial layer of human aortas. RESULTS: IGF-I strongly induced migration of the four cell lines through IGF-IR. In contrast, insulin and IGF-II only caused a significant increase of IRA VSMC migration which might be favored by the formation of IRA/IGF-IR receptors. Additionally, a specific IGF-IR inhibitor, picropodophyllin, completely abolished insulin- and IGF-II-induced migration in IRB, but not in IRA VSMCs. A significant increase of IRA and IGF-IR, and VSMC migration were observed in fibrous plaques from 24-week-old ApoE-/- mice. Finally, we observed a marked increase of IGF-IR, IGF-I and IGF-II in media from fatty streaks as compared with both healthy aortas and fibrolipidic lesions, favoring the ability of medial VSMCs to migrate into the intima. CONCLUSIONS: Our data suggest that overexpression of IGF-IR or IRA isoform, as homodimers or as part of IRA/IGF-IR hybrid receptors, confers a stronger migratory capability to VSMCs as might occur in early stages of atherosclerotic process.

Energy content of reduced-fat dried distillers grains with solubles for lactating dairy cows.

Eight Holstein and 8 Jersey multiparous, lactating cows were used to complete 56 energy balances to determine the energy content of reduced-fat dried distillers grains with solubles (RFDDGS). A repeated switchback design was used to compare treatments with and without RFDDGS. Diets consisted of 24.2% corn silage, 18.4% alfalfa hay, 6.94% brome hay with either 22.9% rolled corn or 14.8% soybean meal (control), or 8.95% rolled corn, 28.8% RFDDGS, and 0% soybean meal [Co-P; dry-matter (DM) basis]. The inclusion of RFDDGS did not affect DM intake, averaging 21.4 ± 0.53 kg of DM for all cows, but milk production tended to increase from 29.8 to 30.9 ± 1.46 kg/d for control and Co-P treatments, respectively. Milk fat percentage and energy-corrected milk did not differ between treatments, averaging 4.33 ± 0.14% and 34.1 kg/d, respectively. Milk protein was significantly decreased by the Co-P treatment (3.56 and 3.41 ± 0.08% for control and Co-P treatments), but protein yield was not affected. Milk energies were 1.40 Mcal/d greater with Co-P. Energy lost as methane was reduced by 0.31 Mcal/d with the addition of RFDDGS to the diet. Heat loss averaged 29.9 ± 0.55 Mcal/d and was not different between diets. Average energy retained as tissue energy was -2.99 ± 0.93 Mcal/d and did not differ between treatments. Intake of digestible and metabolizable energy were not different between the control and Co-P treatments, averaging 2.68 and 2.31 Mcal/kg of DM, respectively. The net energy of lactation values of control and Co-P diets were calculated to be 1.43 and 1.47 Mcal/kg of DM, respectively. These energy estimates suggest greater energy content of diets containing RFDDGS than diets containing a mixture of corn and soybean meal in lactating dairy cows.

Change of the reaction pattern by methodological variations in a multicomponent assembly promoted by Ni complexes.

The pi-allylnickel complex formed by the addition of trimethylsilyl chloride (TMSCl) to a mixture of [Ni-(cod)2] (cod = 1,5-cyclooctadiene) and a vinyl ketone (Mackenzie complex) carbometalates an acetylene in a completely regioselective manner resulting in the formation of the corresponding vinyl nickel species. This intermediate is capable of controlled quenching in a variety of ways to give different types of compounds: under a CO atmosphere, an acylnickel species is formed that ensues from the carbometalation of the enol ether double bond to form cyclo-pentenone derivatives. Alternatively, if acetylene is present in excess and CO is absent, another acetylene moiety will replace the CO and cyclohexadienes will result instead. Finally, if only an excess of the vinyl ketone is used, the product from a slow double addition of the vinyl ketone across the triple bond is formed. The regioselectivities obtained by the present method are different from those obtained by the involvement of nickel acyclopentadienes as intermediates when the order of addition is reversed.