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Identify a novel proinsulin-associated locus and demonstrate that whilst proinsulin levels are associated with carotid intima media thickness measures, proinsulin per se is unlikely to have a causative effect on cIMT.
Data suggest that both a KATP channel-dependent triggering pathway (that induces a [Ca2 (show CA2 Proteins)+]i rise in beta-cells) and an amplifying pathway (that augments the effect of Ca2 (show CA2 Proteins)+ on exocytosis) are crucial for control of insulin secretion in human islets; these studies used cultured pancreatic islets from multiorgan donors exposed to a variety of pharmacological agents.
In the present study, the protein inhibitor of activated STAT (show STAT1 Proteins) Y (PIASy (show PIAS4 Proteins)) was identified as a novel Isl1 (show ISL1 Proteins)-interacting protein. Furthermore, PIASy (show PIAS4 Proteins) and Isl1 (show ISL1 Proteins) upregulate insulin gene expression and insulin secretion in a dose-dependent manner by activating the insulin promoter.
Muscle-related indices positively correlated with C-peptide, which showed endogenous insulin reserve
Data suggest that corticosterone and cortisol suppress voltage-dependent Ca2+ channel function and Ca2+ fluxes in beta-cells; however, insulin secretion, maximal ATP/ADP responses to glucose, and beta-cell identity/differentiation are all unaffected by these glucocorticoids.
In long-standing models, glucose is viewed as a primary stimulator of insulin secretion; recent models postulate that glucose activates a cell-surface receptor, namely the glucose-sensing receptor, on insulin-secreting cells. [REVIEW]
Data suggest that beta-cell insulin secretory granules, unlike neuronal synaptic vesicles, exhibit biphasic secretory mechanism that requires additional distinct features in exocytosis; beta-cell insulin exocytotic events appear to be mediated by Munc18/SNARE (show NAPA Proteins) protein complexes distinct from those involved in predocking/fusion of insulin secretory granules with plasma membrane. [REVIEW]
Data suggest that glucose-stimulated insulin secretion involves interplay between metabolic and cationic events involving small G-proteins; activation of these signaling proteins promotes cytoskeletal remodeling, transport and docking of insulin granules on the plasma membrane for exocytotic secretion of insulin. [REVIEW]
Data suggest that insulin secretory granule turnover consists of several highly regulated processes allowing for proper beta-cell function and insulin secretion. [REVIEW]
Data suggest that cAMP acts as amplifier of insulin secretion triggered by Ca2 (show CA2 Proteins)+ elevation in beta-cells; both messengers are also positive modulators of glucagon (show GCG Proteins) release from alpha-cells, but in this case cAMP signaling may be the important regulator and Ca2 (show CA2 Proteins)+ signaling has a more permissive role. [REVIEW]
Study used well-tempered bias exchange metadynamics simulations to determine the equilibrium ensembles of an insulin molecule under amyloidogenic conditions of low pH and high temperature. The folded state of a single insulin molecule was shown to be the most stable, longest-lived state even under amyloidogenic conditions.
The findings are consistent with previous studies that indicate a link between Na,K-ATPase (show ATP1A1 Proteins) activity and SFK signaling.
PTPLAD1 (show PTPLAD1 Proteins) and AMPK (show PRKAA1 Proteins) are rapidly compartmentalized within the plasma membrane (PM) and Golgi/endosome fractions after insulin stimulation and that ATIC (show ATIC Proteins) later accumulates in the Golgi/endosome fraction.
Pdx-1 (show PDX1 Proteins), MafA (show MAFA Proteins) and NeuroD1 (show NEUROD1 Proteins) bind to the A, C and E elements in the insulin promoter and regulate the transcriptional activity of the insulin promoter.
The interplay of the adiponectin system, TNFalpha (show TNF Proteins) and insulin at a transcriptional level and, their effects on the adipogenic transcription factor PPARgamma (show PPARG Proteins), as well as on the activation of main insulin signaling pathways, is reported.
Thermodynamics of insulin unfolding have been quantified by differential scanning calorimetry and thermal unfolding measurements to determine the extent and nature of their stabilization of the insulin hexamer.
Exposing the hydrophobic core of insulin can induce the increase of amyloidogenicity and formation of higher-order polymerized fibrils, which is less toxic to membranes.
Data suggest that a mutation in INS (C94Y) results a transgenic disease model for the investigation of permanent neonatal diabetes.
The results show that modulation of plasma insulin levels by dietary carbohydrates seems possible in anabolic sows, but IGF-I (show IGF1 Proteins) levels are less easily modified.
insulin increased GCLc (show GCLC Proteins) promoter activity, which required a prerequisite increase or decrease in medium glucose
Insulin signaling role in skeletal muscle atrophy and autophagy in in transition and postpartum period
Differences between human and bovine insulin kinetics under shear
increased sensitivity to glucose clearance and skeletal muscle insulin signaling during dietary restriction
Hormonal gene expression involved in residual feed intake in dairy cows may be related to the molecular regulation of the leptin (show LEP Proteins)-NPY (show NPY Proteins) and insulin signaling pathways.
Raman spectra of amino acids by Density Functional Theory method have been calculated. Experimental Raman spectra of insulin has been done. The simulated Raman spectrum of insulin is obtained from amino acid spectrum.
Contains Binding kinetics for insulin binding
Using synchrotron radiation (SR), the crystal structures of T6 bovine insulin complexed with Ni(2 (show VMP1 Proteins)+) and Cu(2+) were solved to 1.50 and 1.45 A resolution, respectively.
The present study examined the effect of insulin-mediated activation of the mammalian target of rapamycin (show FRAP1 Proteins) complex 1 (MTORC1) signaling network on the proliferation of primary culture of theca-interstitial (T-I) cells.
In-situ spectroscopic investigation of ultrasonic assisted unfolding and aggregation of insulin.
insulin supports early initiation of the mesodermal factor Brachyury (show TBX1 Proteins) and the signalling molecules Wnt3a (show WNT3A Proteins) and Wnt4 (show WNT4 Proteins) as well as the progression of mesoderm formation
Data show that type 1 diabetic blastocyst did not express insulin mRNA.
Data (including data from studies using knockout mice) suggest that Ins1 and Ins2 are required for pancreatic beta-cell maturation; thus, Ins1 and Ins2 are needed for normal beta-cell development and for maintenance of normal beta-cell function.
cTAGE5 deletion in pancreatic beta cells impairs proinsulin trafficking and insulin biogenesis in mice.
These results suggest that prolonged exposure to hyperglycemia in the Ins2(Akita+/-) mice leads to progressive testicular disruption mediated by testicular activin activity, rather than hormonal dysregulation.
report that EndMTs occur in the diabetic endothelium of Ins2Akita/wt mouse, and show that induction of sex determining region Y-box 2 (Sox2 (show SOX2 Proteins)) is a mediator of excess BMP signaling that results in activation of EndMTs and increased vascular calcification
Transplantation of transduced hematopoietic stem cells (HSCs) expressing proinsulin II prevents diabetes development.
Wnt3a increased the expression of NeuroD1 and Ins2 in the hypothalamus.
Data suggest that resveratrol acts on differentiating preadipocytes by inhibiting insulin signaling, mitochondrial biogenesis, and lipogenesis.
have characterized the distinctive sex-specific phenotypes exhibited by the ApoE(-/-):Ins2(+/Akita) mouse model and present evidence for the action of sex hormones on pancreatic beta-cell function
Data indicate that Src homology-2 domain containing protein B (SHB) deficiency causes a chronic increase in beta-cell focal adhesion kinase (FAK) activity that perturbs the normal insulin secretory characteristics of beta-cells.
Mouse Ins2 and Ins1 promoters were transiently activated in mouse fetal hepatocytes of embryonic days 13.5 and 16.5, respectively.
Temporal and spatial expression of two insulin genes (insa and insab) during early developmental stages.
These findings suggest that GHRL (show GHRL Proteins) regulates INS synthesis by mediating its action on growth hormone secretagogue-receptor (show GHSR Proteins) in the central nervous system and partly involved in carbohydrate-glycogen (show GYS2 Proteins) metabolism.
Our results indicate that in adult tilapia insulin expression is not restricted to the endocrine pancreatic cells, but also occurs in endocrine cells of the pituitary gland and in the neuronal cells of the brain.
After removal of the precursor signal peptide, proinsulin is post-translationally cleaved into three peptides: the B chain and A chain peptides, which are covalently linked via two disulfide bonds to form insulin, and C-peptide. Binding of insulin to the insulin receptor (INSR) stimulates glucose uptake. A multitude of mutant alleles with phenotypic effects have been identified. There is a read-through gene, INS-IGF2, which overlaps with this gene at the 5' region and with the IGF2 gene at the 3' region. Alternative splicing results in multiple transcript variants.