Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.59 (MIP)
 4,906 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cDNA clone encoding molluscan insulin-related peptide V (MIP V) was isolated from a cDNA library of the central nervous system (CNS) of the freshwater snail, Lymnaea stagnalis, using a heterologous screening with a previously identified MIP II cDNA. The MIP V cDNA encodes a preprohormone resembling the organization of preproinsulin, with a putative signal sequence, and an A and B chain, however, in this case connected by two distinct C peptide, C alpha and C beta, instead of one single C peptide. This phenomenon, which is shared by the MIP II precursor, represents a new development in the prohormone organization of peptides belonging to the insulin superfamily. The A and B chains of MIPs V, I and II, differ remarkably in primary structure; in contrast, the C alpha peptide domains are almost identical. MIP V has only limited sequence similarity with insulins and related peptides. Both MIP V and I exhibit structural features, which make them a unique class of the insulin superfamily. The MIP I, II and V genes are expressed in a single type of neuron: the growth controlling neuroendocrine light green cells of the Lymnaea CNS.
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PMID:Characterization of a cDNA clone encoding molluscan insulin-related peptide V of Lymnaea stagnalis. 132 19

The body growth controlling cerebral neuroendocrine light green cells of the freshwater snail, Lymnaea stagnalis, express various members of a gene family encoding different though related prepromolluscan insulin-related peptides. In the present study, molluscan insulin-related peptide I (MIP I) together with the corresponding connecting peptide, C alpha peptide, have been isolated and structurally identified. MIP I is a heterodimer of A and B chains bonded by disulphide bridges. Two isoforms of MIP I could be discerned. Mass spectrometry revealed that of one form both the A and B chains have N-terminal pyroglutamyl residues, whereas of the other form only the B chain has such residues. After removal of the pyroglutamyl residues with pyroglutamate aminopeptidase, followed by disulphide bond cleavage and pyridylethylation of cysteine residues, the sequences of MIP I have been determined using Edman degradation as: A chain: (p)QGTTNIVCECCMKPCTLSELRQYCP; B chain: pQPSACNINDRPHRRGVCGSALADLVDPACSSSNGPA. The C alpha peptide has also been isolated and its sequence was determined as NAETDLDDPLRNIKLSSESALTYLY. These sequences are in agreement with those predicted by a cDNA sequence encoding preproMIP I, with the exception that the two C-terminal amino acids of the B chain are posttranslationally removed.
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PMID:Purification and sequencing of molluscan insulin-related peptide I (MIP I) from the neuroendocrine light green cells of Lymnaea stagnalis. 152 14

Two groups of cerebral dorsal cells of the pulmonate snail Planorbarius corneus stain positively with antisera raised against synthetic fragments of the B- and C-chain of the molluscan pro-insulin-related prohormone, proMIP-I, of another pulmonate snail, Lymnaea stagnalis. At the light-microscopic level the somata of the dorsal cells and their axons and neurohemal axon terminals in the periphery of the paired median lip nerves are immunoreactive with both antisera. Furthermore, the canopy cells in the lateral lobes of the cerebral ganglia are positive. In addition, MIPB-immunoreactive neurons are found in most other ganglia of the central nervous system. At the ultrastructural level, pale and dark secretory granules are found in somata and axon terminals of the dorsal cells. Dark granules are about 4 times as immunoreactive to both antisera as pale granules. Release of anti-MIPB- and anti-MIPC-immunopositive contents of the secretory granules by exocytosis is apparent in material treated according to the tannic acid method. It is concluded that the dorsal and canopy cells synthesize a molluscan insulin-related peptide that is packed in the cell body into secretory granules and that is subsequently transported to the neurohemal axon terminals and released into the hemolymph by exocytosis. Thus, MIP seems to act as a neurhormone on peripheral targets. On the basis of the analogy between the dorsal cells and the MIP-producing cells in L. stagnalis, it is proposed that the dorsal cells of P. corneus are involved in the control of body growth and associated processes.
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PMID:Light- and electron-microscopic immunocytochemistry of a molluscan insulin-related peptide in the central nervous system of Planorbarius corneus. 157 61

The formation of neurites in isolated neurones of the snail Lymnaea stagnalis in primary culture was studied. The insulin-related neuropeptide (MIP: Molluscan insulin-related peptide) produced by the neuroendocrine light green cells (LGCs) of Lymnaea stimulated neurite formation, both in isolated unidentified central neurons and in the LGCs. The effect of MIP was dose dependent. It was significant from the second day of culture and amounted up to an 8-fold increase in neurite outgrowth after 3 days. The results add a functional aspect to the evolutionary relationship of MIP with mammalian insulin and insulin-related peptides and suggest that the LGCs, which stimulate growth, are also involved in development of the nervous system.
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PMID:Molluscan insulin-related neuropeptide promotes neurite outgrowth in dissociated neuronal cell cultures. 233 Jan 29

Egg laying in the hermaphrodite freshwater snail Lymnaea stagnalis is a highly complex activity, including a series of internal activities (ovulation, egg and egg mass formation) which are closely correlated to a pattern of behaviours (alteration of locomotion and feeding, specific postures, oviposition). In this snail egg laying is induced by the neuroendocrine caudodorsal cells (CDCs), consisting of two homogeneous clusters at a total of 100 neurons. At egg laying these neurons release their products during a 60 min period of firing. The genes coding for these products have been cloned and characterized. There are two genes, CDCH-I and -II. Each gene codes for 12 peptides; one of these is the ovulation hormone (CDCH). The genes display over 90% homology. The most striking difference is a 17 bp deletion near the carboxy-terminal region. With immunocytochemistry and in situ hybridization both CDCH genes appeared to be expressed in the CDC and in paired groups of ectopic CDC-like neurons in the pleural ganglia, while a group of small neurons in the cerebral ganglia expresses the CDCH-I gene only. In addition, a widespread expression of the CDCH genes has been demonstrated in peripheral tissues. In the female part of the reproductive tract neurons were found to express the CDCH-I gene. In the male part of the tract exocrine secretory cells express the CDCH-I or -II gene. The gene products are secreted into the male tract and transferred to the female partner during copulation. Finally, sensory neurons in the head skin and mantle edge were found to express the CDCH-I gene. The presence of insulin-related peptides has been demonstrated in the brain as well as the digestive system of Lymnaea. The brain insulin-related peptides are produced in 4 groups of 50 giant neurons each (Light green cells, LGC). These neurons are involved in various physiological activities, related to body growth and glycogen metabolism. The major gene products expressed in the LGC have been cloned and characterized. It appeared that the predicted proteins represent three types of insulin-related molecules (MIP, molluscan insulin-related peptide). In these MIPs, those elements important in the determination of the tertiary structure, have been conserved. The MIP of the digestive system has been characterized up to now only at the peptide level. The snail gut MIP is more hydrophobic compared to bovine insulin. Cells containing MIP have been identified immunocytochemically in the gut epithelium.
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PMID:Central and peripheral expression of genes coding for egg-laying inducing and insulin-related peptides in a snail. 251 Jul 86

Although insulins and structurally related peptides are found in vertebrates as well as in invertebrates, it is not clear whether the genes encoding these hormones have emerged from a single ancestral (insulin)-type of gene or, alternatively, have arisen independently through convergent evolution from different types of gene. To investigate this issue, we cloned the gene encoding the molluscan insulin-related peptide III (MIP III) from the freshwater snail, Lymnaea stagnalis. The predicted MIP III preprohormone had the overall organization of preproinsulin, with a signal peptide and A and B chains, connected by two putative C peptides. Although MIP III was found to share key features with vertebrate insulins, it also had unique structural characteristics in common with the previously identified MIPs I and II, thus forming a distinct class of MIP peptides within the insulin superfamily. MIP III is synthesized in neurones in the brain. It is encoded by a gene with the overall organization of the vertebrate insulin genes, with three exons and two introns, of which the second intron interrupts the coding region of the C peptides. Our data therefore demonstrate that in the Archaemetazoa, the common ancestor of the vertebrates and invertebrates, a primordial peptide with a two-chain insulin configuration encoded by a primordial insulin-type gene must have been present.
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PMID:Evolutionary conservation of the insulin gene structure in invertebrates: cloning of the gene encoding molluscan insulin-related peptide III from Lymnaea stagnalis. 824 Jun 68

The morphology of cells immunoreactive to an antibody against molluscan insulin-related peptide (MIP-IR) was studied in two species of terrestrial snail: Helix lucorum L. and Eobania vermiculata L. Immunocytochemical staining with this antibody to MIP revealed 100-130 cells in the postcerebrum, located in two clusters with common pathways in the dorsal body nerve and the cerebral artery nerve. About 75% of the MIP-IR cells were labeled by backfilling of the dorsal body nerve in Helix and Eobania; the corresponding figures for labeling by backfilling of the cerebral artery nerve were about 60% in Helix and 30% in Eobania. Upon intracellular staining of neurons of the dorsomedial postcerebrum, where most of the MIP-IR cells were located, it was found that they projected either in the dorsal body nerve or in the cerebral artery nerve or in both. The obtained data suggest that growth and reproduction processes (both functions were attributed to the insulin-related peptide-containing neurons) are regulated by the two, partially coinciding subsets of postcerebral MIP-IR neurons with different types of branching.
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PMID:Morphological basis for coordination of growth and reproduction processes in the CNS of two terrestrial snails. 1549 Jan 31

Type 1 (insulin-dependent) diabetes mellitus is an autoimmune disease characterized by the failure to synthesize or secrete insulin, and diabetics are likely to suffer complications that include kidney and heart disease, as well as loss of sight, angiopathy, tissue hypoxia, reduction in organ blood flow, impaired wound healing, respiratory infections, arteriosclerosis, etc., thus diabetes very closely resembles a state of chronic hypoxia. It is now well recognized that hypoxia is an important environmental stimulus capable of modulating the expression of many genes involved in energy metabolism. The diabetic metabolic stress resulting from impaired energy metabolism, which produce altered production of inflammatory mediators, may increase the risk of oxidative injury. The aim was to investigate whether production of MIP-2 and MCP-1 are implicated in the pathogenesis of diabetes, and if the regulatory effects of these chemokines are affected by hypoxia. Two groups of rats, diabetic and non-diabetic, were kept in normoxic room air conditions or subjected to chronic hypoxia. Expression and production of chemokines were measured by RT-PCR and ELISA assay. In diabetic rats, we found a marked increase of MCP-1 when compared with non-diabetic rats (783.5+/- 49 versus 461.9 +/- 27), while no significant differences were detected for MIP-2 levels. Hypoxia selectively modulated chemokines production, since MCP-1 expression and production was up-regulated in the diabetic groups (783.5+/- 49 versus 461.9+/- 27), but down-regulated MIP-2 expression and production (87.8+/- 23 versus 522.1+/- 72). Our data point to MCP-1 and MIP-2 as important components in the pathophysiology of diabetes, and hypoxia is an important and potent environmental stimulus capable of modulating the expression and production of these chemokines.
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PMID:MCP-1 and MIP-2 expression and production in BB diabetic rat: effect of chronic hypoxia. 1613 91

Although Staphylococcus aureus is a major pathogen implicated in diabetic foot infections, little is known about the pathogenesis of this disease. A model of S. aureus infection in the hindpaw of nonobese diabetic (NOD) mice was developed. The experimental infection was exacerbated in diabetic mice (blood glucose levels > or =19 mmol/l) compared with nondiabetic mice, and the diabetic animals were unable to clear the infection over a 10-day period. Insulin-mediated control of glycemia in diabetic mice resulted in enhanced clearance of S. aureus from the infected tissue. Diabetic mice showed reduced tissue inflammation in response to bacterial inoculation compared with nondiabetic NOD animals, and this was consistent with the novel finding of significantly decreased tissue levels of the chemokines KC and MIP-2 in diabetic mice. Blood from nondiabetic and diabetic NOD mice killed S. aureus in vitro, whereas the bacteria multiplied in blood from diabetic mice with severe hyperglycemia. The impaired killing of S. aureus by diabetic mice was correlated with a diminished leukocytic respiratory burst in response to S. aureus in blood from diabetic animals. This animal model of hindpaw infection may be useful for the analysis of host defects in innate immunity that contribute to recalcitrant diabetic foot infections.
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PMID:The pathogenesis of Staphylococcus aureus infection in the diabetic NOD mouse. 1618 91

Glucose regulates pancreatic islet alpha-cell glucagon secretion directly by its metabolism to generate ATP in alpha-cells, and indirectly via stimulation of paracrine release of beta-cell secretory products, particularly insulin. How the cellular substrates of these pathways converge in the alpha-cell is not well known. We recently reported the use of the MIP-GFP (mouse insulin promoter-green fluorescent protein) mouse to reliably identify islet alpha- (non-green cells) and beta-cells (green cells), and characterized their ATP-sensitive K(+) (K(ATP)) channel properties, showing that alpha-cell K(ATP) channels exhibited a 5-fold higher sensitivity to ATP inhibition than beta-cell K(ATP) channels. Here, we show that insulin exerted paracrine regulation of alpha-cells by markedly reducing the sensitivity of alpha-cell K(ATP) channels to ATP (IC(50) = 0.18 and 0.50 mM in absence and presence of insulin, respectively). Insulin also desensitized beta-cell K(ATP) channels to ATP inhibition (IC(50) = 0.84 and 1.23 mM in absence and presence of insulin, respectively). Insulin effects on both islet cell K(ATP) channels were blocked by wortmannin, indicating that insulin acted on the insulin receptor-phosphatidylinositol 3-kinase signaling pathway. Insulin did not affect alpha-cell A-type K(+) currents. Glutamate, known to also inhibit alpha-cell glucagon secretion, did not activate alpha-cell K(ATP) channel opening. We conclude that a major mechanism by which insulin exerts paracrine control on alpha-cells is by modulating its K(ATP) channel sensitivity to ATP block. This may be an underlying basis for the proposed sequential glucose-insulin regulation of alpha-cell glucagon secretion, which becomes distorted in diabetes, leading to dysregulated glucagon secretion.
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PMID:Insulin regulates islet alpha-cell function by reducing KATP channel sensitivity to adenosine 5'-triphosphate inhibition. 1645 78


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