Form a a-helix that has the propensity to interact with the lipid membrane. Presumably, upon translation of Xbp1unspliced, the HR2 on the nascent polypeptide associates with the ER membrane and brings the Xbp1 mRNA-ribosome-nascent chain complex to the vicinity of Ire1, facilitating Ire1-mediated splicing. Xbp1spliced lacks HR2 due to the frameshift that occurs upon Ire1-mediated splicing event and localizes predominantly in the nucleus, where it is active as transcription factor. In addition to HR1 and HR2, there is another motif in Xbp1unspliced that is also important for proper localization of Xbp1 mRNA at the ER membrane. The C-terminal region of Xbp1unspliced is essential for translational pausing, just when HR2 is protruding from the ribosome exit tunnel. Presumably, pausing of translation stabilizes the Xbp1 mRNAribosome-nascent chain complex in the vicinity of the ER membrane, giving the opportunity for activated Ire1 to cleave Xbp1 mRNA. In Drosophila, a Xbp1-EGFP ER stress reporter lacking the HR2 and CTR of Xbp1unspliced was found to be activated under a variety of ER stress stimuli, 
including some specific physiological conditions during development, by the addition of ER stressinducing drugs to tissues and cells or by using mutations that cause the accumulation of misfolded proteins in the ER. In these studies Xbp1-EGFP was expressed with the UAS/GAL4 Homatropine Bromide system, but GFP is only observed upon the Ire1-dependent splicing of the Xbp1 intron present in the reporter. A modified “high gain” version of Xbp1-EGFP, where HR2, CTR and the 39 UTR of Xbp1unspliced were included in the reporter, greatly increased the reporter sensitivity and GFP expression upon ER stress. However, in all these cases, and due to the nature of the UAS/GAL4 system, Xbp1-EGFP was likely to be over-expressed in tissues or cells, which may overload the mechanisms regulating Xbp1 mRNA targeting to the ER membrane. The postprandial dysmetabolism plays an important role in the pathogenesis of type 2 diabetes and its complications. Abnormal postprandial elevation of plasma glucose and lipids is closely tied to insulin resistance and may occur in the absence of overt T2D. Postmeal hyperglycemia and hyperlipidemia increases the risk of cardiovascular Clofentezine diseases in diabetic patients and may predict cardiovascular risk more strongly than fasting values or even long-term parameters such as glycated hemoglobin. In patients with T2D, acute hyperglycemia and hypertriglyceridemia lead to endothelial dysfunction, induce oxidative stress, increase the inflammatory milieu, affect coagulation, and, probably, impair secretion and diminish effect of gastrointestinal peptides. Incretin hormones, which are released from the gastrointestinal tract in response to nutrient ingestion to enhance glucosedependant insulin secretion, aid the overall maintenance of glucose homeostasis through slowing of gastric emptying, inhibition of glucagon secretion and control of body weight. Two incretins – glucagon-like peptide-1, and gastric inhibitory peptide – were found to exert major glucoregulatory actions. The impaired incretin effect may contribute to delayed and attenuated insulin response during a meal in T2D. The mechanism which would make clear the diminished effect of gastrointestinal hormones in patients with T2D is not completely understood. It is not clear whether the loss of incretin secretion is a cause or rather a consequence of hyperglycaemia. Appetite hormones, ghrelin and leptin, are also known to play a prominent role in glucose homeostasis and the regulation of energy.