{'fraction_non_alphanumeric': 0.0280974043350281, 'fraction_numerical': 0.014985282312014986, 'mean_word_length': 5.11783960720131, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Is there evidence for phospho-oligosaccharides as insulin mediators?

Insulin belongs to the disulfide-rich subclass of group 3 small ot/fi cytokines, which includes the insulin-like growth factors (IGF) 1 and 2, relaxin and bombyxin, and contains a conserved set of three disulfide bonds linking three short a-helices (Nicola, 1994). All insulin class cytokines/hormones bind to class II covalent tyrosine kinase receptors (Figure 1), and while the IGFs can also bind to the mannose-6-phosphate receptor, the biological relevance of this interaction is unclear at the present time. Insulin has a number of potent biological effects on metabolic processes including many aspects of glucose and lipid primary metabolism. The established downstream mode of signal transduction for insulin is somewhat unusual. Engagement of the insulin receptor by insulin results in activation of tyrosine kinase activity in the receptor's (3-chain. This activity is able to autophosphorylate multiple tyrosine residues on the companion (J-chain in the heterotetramer receptor complex, but unlike many other tyrosine kinase receptors, this phosphorylation does not result in the direct creation of SH2 or SH3-domain binding sites. Instead the activated insulin receptor is capable of phosphorylating two related polypeptides, insulin receptor substrates 1 and 2 (IRS-1 and 2), on multiple sites. IRS-1 and IRS-2 are able to interact with a large number of SH2 and SH3-domaincontaining downstream effectors including Grb2 and phosphatidyl inositol(PI)-3 kinase (see White and Kahn 1994; Waters and Pessin, 1996, and references therein) and provides a link into the ras/MAP kinase pathway. Interestingly both IRS-1 and IRS-2 contain pleckstrin homology domains at their N-termini, potentially allowing these molecules to interact with PI (Myers et al, 1995). IRS-1 and IRS-2 are also substrates for several members of the Janus kinase family which themselves are associated with signal transduction pathways from members of the interleukin (IL-4 and 9), interferon (IFN-a and JPN-7), and growth hormone families thereby providing enormous potential for flexibility in signal propagation. Not all of the great many biological effects of insulin have been definitively shown to progress through IRS-1 or -2, but the majority of insulin actions have been tied in, to greater or lesser extent, with one or more of the established signal transduction pathways. Obviously most of the gaps in our understanding of these pathways are just incomplete data, but the concept of a novel mediator for insulin action, that is, a molecule that can act as an insulinomimetic and is in some manner uniquely distinct from conventional signaling components, is quite old and predates molecular understanding of receptortype tyrosine kinase pathways (Lamer, 1972). Mediators with many different biochemical properties have been proposed, ranging from peptides, based on the ability of proteases to mimic insulin action (Seals and Czech 1980) to glycopeptides and free oligosaccharides amongst other more esoteric candidates. Clearly any mediator must either act in parallel to the IRS-1 and -2 system or downstream of it. A persistent mediator candidate, first implicated over 10 years ago but still being actively researched by some workers is a phosphooligosaccharide (POS) fragment of a glycosylphosphatidylinositol (GPI) lipid proposed to be present in a number of mammalian cell types and is the subject of this minireview. The general structure of the canonical anchor type GPI molecule is shown in Figure 2. Below, I will consider the biochemical data that have been presented for and against a role for a POS factor in insulin signaling over the last decade and a half.