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  • Glucose-lowering and insulin-sensitizing actions of exendin-4: studies in obese diabetic (ob/ob, db/db) mice, diabetic fatty Zucker rats, and diabetic rhesus monkeys (Mac ... 10331407

    Exendin-4 is a 39 amino acid peptide isolated from the salivary secretions of the Gila monster (Heloderma suspectum). It shows 53% sequence similarity to glucagon-like peptide (GLP)-1. Unlike GLP-1, exendin-4 has a prolonged glucose-lowering action in vivo. We compared the potency and duration of glucose-lowering effects of exendin-4 and GLP-1 in hyperglycemic db/db and ob/ob mice. Whereas reductions in plasma glucose of up to 35% vanished within 1 h with most doses of GLP-1, the same doses of exendin-4 resulted in a similar glucose-lowering effect that persisted for >4 h. Exendin-4 was 5,530-fold more potent than GLP-1 in db/db mice (effective doses, 50% [ED50s] of 0.059 microg/kg +/-0.15 log and 329 microg/kg+/-0.22 log, respectively) and was 5,480-fold more potent in ob/ob mice (ED50s of 0.136 microg/kg+/-0.10 log and 744 microg/kg+/-0.21 log, respectively) when the percentage fall in plasma glucose at 1 h was used as the indicator response. Exendin-4 dose-dependently accelerated glucose lowering in diabetic rhesus monkeys by up to 37% with an ED50 of 0.25 microg/kg +/-0.09 log. In two experiments in which diabetic fatty Zucker rats were injected subcutaneously twice daily for 5-6 weeks with doses of exendin-4 up to 100 microg x rat(-1) x day(-1) (approximately 250 microg/kg), HbA1c was reduced relative to saline-injected control rats. Exendin-4 treatment was also associated in each of these experiments with weight loss and improved insulin sensitivity, as demonstrated by increases of up to 32 and 49%, respectively, in the glucose infusion rate (GIR) in the hyperinsulinemic euglycemic clamp. ED50s for weight loss and the increase in clamp GIR were 1.0 microg/kg+/-0.15 log and 2.4 microg/kg+/-0.41 log, respectively. In conclusion, acute and chronic administration of exendin-4 has demonstrated an antidiabetic effect in several animal models of type 2 diabetes.
    Document Type:
    Reference
    Product Catalog Number:
    RI-13K
    Product Catalog Name:
    Rat Insulin RIA

  • Cereal type and heat processing of the cereal affect nutrient digestibility and dynamics of serum insulin and ghrelin in weanling pigs. 21478449

    The effects of feeding corn or rice, either raw or heat processed (HP), on apparent total tract digestibility (ATTD) and apparent ileal digestibility (AID) of nutrients and insulin and ghrelin concentrations in the serum were studied in young pigs. Pigs were weaned at approximately 23 ± 3 d of age and weighed 7.4 ± 1.2 kg. Each of the 4 treatments was replicated 9 times and the experimental unit was a pig individually housed. Pigs (5 males and 4 females/treatment) were fed their respective diets ad libitum from 23 to 47 d of age. At 37 d of age, the effects of dietary treatments on the fasting and postprandial concentrations of insulin and total and acylated ghrelin were studied. The ATTD of OM, GE, and ether extract (EE) was, respectively, 4.3, 5.4, and 3.6% greater (P < 0.05) for the rice than for the corn diets but CP digestibility was not affected. Similar results were observed for AID. Heat processing of the cereal increased (P < 0.05) the ATTD by 2.1% for OM, 3.2% for GE, 7.1% for EE, and 2.2% for CP and tended to increase the AID of CP (P = 0.06) and starch (P = 0.09). The postprandial serum insulin response was greater and prolonged in pigs fed raw rice than pigs fed raw corn (P < 0.05). Also, the effects of HP on serum insulin response were more pronounced with corn than with rice (cereal x HP, P < 0.05). Total ghrelin concentration was not affected by treatment but acylated ghrelin was greater (P < 0.05) at 6 h postprandial in pigs fed rice than pigs fed raw corn. Feeding rice and HP corn increased nutrient digestibility and insulin response in the early postprandial period and acylated ghrelin response in the late postprandial period compared with feeding raw corn.
    Document Type:
    Reference
    Product Catalog Number:
    Multiple
    Product Catalog Name:
    Multiple

  • Differential expression of chicken hepatic genes responsive to PFOA and PFOS 17560707

    The effects of PFOS and PFOA on the gene expression patterns of chickens that were exposed to either PFOS or PFOA at low doses were investigated with the use of microarray techniques. Twelve Genechip Chicken Genome Arrays were used to study hepatic gene expression in 6-week-old chickens (Gallus gallus) that were exposed to either PFOA (0.1, 0.5, or 5 mg/mL), PFOS (0.02 or 0.1 mg/mL), or a saline vehicle control (0.9% NaCl in Milli-Q water) via subcutaneous implantation of a 2 mL osmotic pump for 4 weeks or for 4 weeks with a further 4 weeks of depuration. Over 240 and 480 genes were significantly affected by PFOS after 4 weeks of exposure and after 4 weeks of exposure with a further 4 weeks of depuration, respectively and over 290 and 320 genes were significantly affected by PFOA, correspondingly. For PFOS, the genes that were affected after 4 weeks of exposure were mainly related to the transport of electrons and oxygen, and the metabolism of lipids and fatty acids; while the genes that were affected after 4 weeks of exposure with a further 4 weeks of depuration were mainly related to the transport of electrons and ions, and protein amino acid phosphorylation and proteolysis. For PFOA, the genes that were affected after 4 weeks of exposure were related to the transport of ions, lipids, and electrons and cytochromes; while the genes that were affected after 4 weeks of exposure with a further 4 weeks of depuration were related to protein amino acid phosphorylation and proteolysis, the transport of ions, and the metabolism of fatty acids and lipids. The results also showed that the gene expression patterns between chickens that were treated with PFOS and those that were treated with PFOA were different, which points to the importance of the separate evaluation of the toxicities of PFOS and PFOA. Specifically, the gene expressions of CYP8B and NOV were studied.
    Document Type:
    Reference
    Product Catalog Number:
    Multiple

  • Anti-Puromycin, clone 12D10, Alexa -2807044

    Document Type:
    Certificate of Analysis
    Lot Number:
    2807044
    Product Catalog Number:
    MABE343-AF488
    Product Catalog Name:
    Anti-Puromycin, clone 12D10, Alexa Fluor® 488 Conjugate Antibody

  • Enhanced histone acetylation in somatic cells induced by a histone deacetylase inhibitor improved inter-generic cloned leopard cat blastocysts. 20708232

    The objective was to determine whether alterations of histone acetylation status in donor cells affected inter-generic SCNT (igSCNT)-cloned embryo development. Leopard cat cells were treated with trichostatin A (TSA; a histone deacetylase inhibitor) for 48 h, and then donor cells were transferred into enucleated oocytes from domestic cats. Compared to non-treated cells, the acetylated histone 3 at lysine 9 (AcH3K9) and histone 4 at lysine 5 (AcH4K5) in the TSA group increased for up to 48 h (P < 0.05). The AcH3K9 signal ratios of igSCNT group was higher than control group 3 h after activation (P < 0.05). Treatment with TSA significantly increased total cell number of blastocysts (109.1 ± 6.9 vs. 71.8 ± 2.9, mean ± SEM), with no significant effects on rates of cleavage or blastocyst development (71.1 ± 2.8 vs. 67.6 ± 2.9 and 12.2 ± 2.6 vs. 11.0 ± 2.6, respectively). When igSCNT cloned embryos were transferred into a domestic cat oviduct and recovered after 8 d, blastocyst development rates and total cell numbers were greater in the TSA-igSCNT group (20.7 ± 3.0% and 2847.6 ± 37.2) than in the control igSCNT group (5.7 ± 2.2% and 652.1 ± 17.6, P < 0.05). Average total cell numbers of blastocysts were approximately 4.4-fold higher in the TSA-igSCNT group (2847.6 ± 37.2, n = 10) than in the control group (652.1 ± 17.6, n = 8; P < 0.05), but were ∼2.9-fold lower than in vivo cat blastocysts produced by intrauterine insemination (8203.8 ± 29.6, n = 5; P < 0.001). Enhanced histone acetylation levels of donor cells improved in vivo developmental competence and quality of inter-generic cloned embryos; however, fewer cells in blastocysts derived from igSCNT than blastocysts produced by insemination may reduce development potential following intergeneric cloning (none of the cloned embryos were maintained to term).
    Document Type:
    Reference
    Product Catalog Number:
    07-352
    Product Catalog Name:
    Anti-acetyl-Histone H3 (Lys9) Antibody

  • Disruption of Caenorhabditis elegans muscle structure and function caused by mutation of troponin I. 14747334

    Caenorhabditis elegans strains mutant for the unc-27 gene show abnormal locomotion and muscle structure. Experiments revealed that unc-27 is one of four C. elegans troponin I genes and that three mutant alleles truncate the protein: recessive and presumed null allele e155 terminates after nine codons; semidominant su142sd eliminates the inhibitory and C-terminal regions; and semidominant su195sd abbreviates the extreme C-terminus. Assays of in vivo muscular performance at high and low loads indicated that su142sd is most deleterious, with e155 least and su195sd intermediate. Microscopy revealed in mutant muscle a prevalent disorder of dense body positioning and a less well defined sarcomeric structure, with small islands of thin filaments interspersed within the overlap region of A bands and even within the H zone. The mutants' rigid paralysis and sarcomeric disarray are consistent with unregulated contraction of the sarcomeres, in which small portions of each myofibril shorten irregularly and independently of one another, thereby distorting the disposition of filaments. The exacerbated deficits of su142sd worms are compatible with involvement in vivo of the N-terminal portion of troponin I in enhancing force production, and the severe impairment associated with su195sd highlights importance of the extreme C-terminus in the protein's inhibitory function.
    Document Type:
    Reference
    Product Catalog Number:
    AP181F
    Product Catalog Name:
    Goat Anti-Mouse IgG Antibody, FITC conjugate, Species Adsorbed