Disease relevance of Isl1

• Isl-1 immunoreactivity was also widely distributed in neurons in both the central and peripheral nervous system, pituitary, and several human pituitary tumors and pheochromocytomas [1].
• DISCUSSION: Islet secretory response was improved despite continued hyperglycemia and severe insulin resistance [2].
• Nerve growth factor induces the expression of the LIM homeodomain transcription factor Isl-1 with the kinetics of an immediate early gene in adult rat dorsal root ganglion [3].
• A DNA sequence coding for 66 amino acid residues containing the C-terminal homeodomain fragment of Isl-1 was expressed as a soluble protein in Escherichia coli [4].
• The transcription factor Isl-1, a protein expressed in subsets of neurons and endocrine cells as well as in neuroblastoma cells, was also expressed in the transplanted tumours, thus further verifying the retained phenotype of the cells under in vivo conditions [5].

High impact information on Isl1

• We conclude that pancreatic islet cells can rapidly activate defence mechanisms against nitric oxide, reactive oxygen intermediates and streptozotocin by culture at 43 degrees C. Islet cell survival is due to the prevention of lethal NAD+ depletion during DNA repair, probably by slowing down poly(ADP-ribose)polymerase activation [6].
• Furthermore, in response to Sonic hedgehog, which is a major inductive signal from the environment for regional specification, neuroepithelial cells that maintain distinct regional identities expressed different sets of ventral-specific genes including Islet-1, Nkx-2.1 and Nkx-2 [7].
• We observed that Kir6.2 protein was expressed de novo in IEC-6 cells expressing both Pdx-1 and Isl-1 but not in cells expressing Pdx-1 alone [8].
• Finally, knockdown of Isl-1 using the iRNA technique resulted in decreased expression of Kir6.2 protein in a rat pancreatic beta-cell line (RIN-5F cells) [8].
• This, together with NF-kappa B-dependent inhibition of Glut-2, pro-hormone convertase-1, and Isl-1 expression, probably contributes to the loss of differentiated beta-cell functions [9].

Chemical compound and disease context of Isl1

• AIM: Islet dysfunction, characterized by the loss of an acute insulin secretory response (AIR) to glucose is a well-established pathology of type 2 diabetes mellitus [10].

Biological context of Isl1

• During early embryogenesis, mAb SAC1 selectively labels a small subset of Isl1-positive motor neurons located exclusively within cervical segments of the spinal cord [11].
• 2. To investigate the regulation of Kir6.2 gene expression, we assessed Kir6.2 expression in IEC-6 cells expressing Pdx-1 and/or Isl-1 [8].
• In contrast, the Gb/Gc sites activated transcription 2-3 fold in wild type InR1-G9 cells, and the isl-1-dependent activation of gene transcription through the Gb/Gc element was eliminated following transfection of isl-1(AS) InR1-G9 cells [12].
• The B-domain, on the other hand, binds an islet cell-specific protein with characteristics similar to those of Isl-1, a transcriptional activator protein that binds to the E2 enhancer of the rat insulin-1 gene [13].
• The transcriptional properties of the proglucagon gene promoter sequences that bind isl-1 (designated Ga, Gb, and Gc) were assessed after transfection of reporter genes into wild type and isl-1-antisense (isl-1(AS)) InR1-G9 islet cells [12].

Anatomical context of Isl1

• In summary, our results indicated that immature intestinal stem cells can differentiate into insulin-producing cells given the ability to express the transcription factors Pdx-1 and Isl-1 [14].
• Islet-1 expression was suprisingly down-regulated in motoneurons and sensory neurons of adult rats after axotomy [15].
• To determine whether the distribution of early differentiating cell types in the ventral neural tube is consistent with the operation of such a mechanism in vivo, the early localization of Isl-1/2+ motor neurons in relation to HNF-3 beta+ floor plate cells has been investigated [16].
• AIM: To explore the possibility of marrow mesenchymal stem cells (MSC) in vitro differentiating into functional islet-like cells and to test the diabetes therapeutic potency of Islet-like cells [17].
• Insulin (INS) immunopositive cells were observed in the peripheral and central portions of the Islet of Langerhans in the pancreas of normal rat [18].

Associations of Isl1 with chemical compounds

• Diabetes-prone inflamed islets had secretions of 0.35 +/- 0.02 ng during the first phase (P < 0.05 vs. WF) and 1.78 +/- 0.29 ng during the second phase (P < 0.05 vs. WF) after 16.7 mM glucose, with 0.24 +/- 0.08 ng.20 min-1 x islet-1 at 2 mM glucose.(ABSTRACT TRUNCATED AT 250 WORDS)[19]
• However, there was a significant 30-70% reduction in the levels of a large number of other islet mRNAs including glucokinase, mitochondrial glycerol-3-phosphate dehydrogenase, voltage-dependent Ca2+ and K+ channels, Ca(2+)-ATPase, and transcription factor Islet-1 mRNAs [20].
• Glucagon release in response to alanine (10 mM) stimulation was also significantly higher in dorsal than in ventral islets (6.38 +/- 1.98 vs. 1.49 +/- 0.89 pg X islet-1 X h-1, respectively; P less than .02) [21].
• 2. Islet homogenates catalysed transamination reactions between 3-phenylpyruvate and L-glutamate, L-leucine, L-norleucine or L-valine [22].
• CONCLUSIONS: Islet graft blood flow was influenced by adenosine, AT II, and nitric oxide inhibition in all animals [23].

Physical interactions of Isl1

• The Isl-1 gene in rat codes for a protein that binds to the insulin gene enhancer and is also involved in regulation of amylin and proglucagon genes [4].

Regulatory relationships of Isl1

• We find that activated RARbeta up-regulates islet-1 expression, whereas activation of RARalpha can either act in combination with RARbeta signalling to maintain islet-1 expression or induce islet-2 expression in the absence of activated RARbeta [24].

Other interactions of Isl1

• These results indicated that combined expression of Pdx-1 and Isl-1 in IEC-6 cells was required for the production of insulin [14].
• RESULTS: Islet HO1 mRNA expression was minimal after overnight culture in G10, slightly increased in G5, and increased by five- to ten-fold in G30 in parallel with a heterogeneous increase in beta-cell HO1 protein expression [25].
• The LIM domain homeobox gene isl-1 is a positive regulator of islet cell-specific proglucagon gene transcription [12].
• These scattered Isl-1-positive cells were doubly labeled with tyrosine kinase receptor A and choline acetyltransferase, which indicated that they were cholinergic neurons [26].
• Numerous Isl-1-positive cells appeared in the medial mantle zone of the developing striatal proper, and they co-expressed the postmitotic neuronal marker, microtubule-associated protein 2 [26].

Analytical, diagnostic and therapeutic context of Isl1

• RESULTS: Islet allografts transplanted alone were rapidly rejected within 5-8 days [27].
• Thus, we studied changes in the expression of islet-1 after axotomy, under the assumption that frequently developmentally regulated factors are reactivated during neuronal regeneration [15].
• We investigated the regulation of islet-1 expression with (i) semi-quantitative reverse transcription polymerase chain reaction and (ii) confocal microscopy in combination with quantitative image analysis [15].
• Using this method, the down-regulation of islet-1 could be demonstrated with a similar sensitivity to that previously shown with radioactive RT-PCR [28].
• CONCLUSION: Islet blood flow stimulation induced by alloxan leads to an increased blood perfusion in all islets, whereas glucose induces a flow increase only in a subgroup of islets [29].

References