IR (Phospho-Tyr1355) ELISA Kit

The aim of this study was to characterize insulin, leptin and IGF-1 profiles after undernutrition in pregnant ewes with different initial body condition (iBCS) and to investigate embryo quality, uterine gene expression and presence and location of proteins during early gestation (day 5). Thirty-six Rasa Aragonesa ewes were divided into 2 groups with different BCS: BCS> 2.75 (high, H, n = 19) and BCS <2.25 (low, I, n = 17) and they were randomly assigned to two nutritional treatments: 1.5 maintenance (M) (control, C) or 0.5 (M) (undernourishment, U) times the daily maintenance requirements establishing four groups: high-iBCS control (HC, n = 9), high-iBCS undernourished (HU, n = 10), low-iBCS control (LC, n = 9) and low-iBCS undernourished (LU, n = 8). High-iBCS ewes presented higher concentration of IGF1, reflecting a better metabolic status in these animals. There was a greater proportion of high-iBCS ewes presenting more than one CL (P < 0.05), and associated greater P4 plasma concentration, number of recovered embryo and a tendency for higher embryo viability rate (P = 0.13). In uterus, undernourished ewes tended to present lower P4 (P = 0.09) and higher E2 concentration (P = 0.10). Inmunostaining of uterine progesterone and estrogen receptors (PR and Eft.a) was not affected by iBCS and nutritional treatment. Ewes with low-iBCS tended to have more INSR mRNA, and undernourished ewes tended to have more IGFBP2 mRNA expression (P < 0.08). An interesting finding was that the uterine response to undernutrition was dependent on iBCS: a higher expression of GHR (P < 0.05) and a tendency in IGFBP5 (P = 0.09) mRNA was found in undernourished than control ewes but only in the high-iBCS group. In summary, the present study demonstrates that the endocrine response and the uterine gene expression to undernutrition depend on the initial body energy reserves (iBCS) and appears to be associated with a differential embryo quality. (C) 2019 Elsevier Inc. All rights reserved.

Obesity-related insulin resistance is associated with fatty liver, dyslipidemia, and low plasma adiponectin. Insulin resistance due to insulin receptor (INSR) dysfunction is associated with none of these, but when due to dysfunction of the downstream kinase AKT2 phenocopies obesity-related insulin resistance. We report 5 patients with SHORT syndrome and C-terminal mutations in PIK3R1, encoding the p85 alpha/p55 alpha/p50 alpha subunits of PI3K, which act between INSR and AKT in insulin signaling. Four of 5 patients had extreme insulin resistance without dyslipidemia or hepatic steatosis. In 3 of these 4, plasma adiponectin was preserved, as in insulin receptor dysfunction. The fourth patient and her healthy mother had low plasma adiponectin associated with a potentially novel mutation, p.Asp231Ala, in adiponectin itself. Cells studied from one patient with the p.Tyr657X PIK3R1 mutation expressed abundant truncated PIK3R1 products and showed severely reduced insulin-stimulated association of mutant but not WT p85 alpha with IRS1, but normal downstream signaling. In 3T3-L1 preadipocytes, mutant p85 alpha overexpression attenuated insulin-induced AKT phosphorylation and adipocyte differentiation. Thus, PIK3R1 C-terminal mutations impair insulin signaling only in some cellular contexts and produce a subphenotype of insulin resistance resembling INSR dysfunction but unlike AKT2 dysfunction, implicating PI3K in the pathogenesis of key components of the metabolic syndrome.