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Higher levels of C-peptide in obese pregnant women is suggestive for hyperinsulinemia.
Here we show that misfolded proinsulin impairs developing beta-cell proliferation without increasing apoptosis. We generated induced pluripotent stem cells (iPSCs) from people carrying insulin (INS) mutations, engineered isogenic CRISPR-Cas9 mutation-corrected lines and differentiated them to beta-like cells
These results suggest that the classical metabolic PI3K pathway and not the canonical proliferation ERK pathway is involved in the insulin/insulin-like growth factor-1-induced increase in crypt proliferation in obese humans, which may contribute to abnormal tissue renewal and function.
Glycated insulin presented altered conformation and more exposed hydrophobic patches than insulin. Formation of oligomeric species and advanced glycated end products (AGEs) were determined. Lower cell viability, higher apoptosis, and more Reactive Oxygen Species were detected upon treatment of cells with glycated insulin.
In a southern Brazilian cohort, C-peptide was associated with obesity indicators, both waist circumference and BMI.
The n-region's positive charge of the signal peptide ensured efficient post-translational translocation of proinsulin.
evidence that insulin resistance disrupts endothelial barrier integrity, decreases eNOS phosphorylation and mitochondrial function, and activates inflammation in lymphatic endothelium.
There was a strong correlation between maternal insulin and infant irisin levels in small for gestational age (SGA) infants, while in large for gestational age (LGA) Infants a strong correlation between infant insulin and leptin levels were found.
There was a significant upregulation of insulin (INS) and INS Receptor expression levels in Alzheimer's disease both prodromal and fully symptomatic, as compared with controls, but not in mild cognitive impairment subjects.
Insulin resistance and prediabetes contribute to the progression of vascular dysfunction and disease in the body and brain. [review]
D-ribose glycation of insulin preserves the structure inhibiting amyloid aggregation.
genetic association studies in population of children in Japan: Data suggest that mutations in INS, HNF1A, HNF4A, and HNF1B likely play critical roles in children with insulin-requiring autoantibody-negative type 1 diabetes in the population studied. (INS = insulin; HNF1A = HNF1 homeobox A; HNF4A = hepatocyte nuclear factor 4 alpha; HNF1B = HNF1 homeobox B)
Insulin signaling pathway protects neuronal cell lines by Sirt3 mediated IRS2 activation.
Insulin promotes progression of colon cancer by upregulation of ACAT1.
Data suggest that serum leptin and insulin levels are associated with retinal microvasculature parameters in healthy children and adolescents; higher cardiometabolic risk factors (high serum leptin, insulin, and insulin resistance) correlate with wider retinal arterioles.
Data, including studies involving single-cell analysis, suggest that insulin-secreting cells exhibit 3 major states regarding unfolded protein response (UPR): (1) low UPR and low insulin gene expression; (2) low UPR and high insulin gene expression; (3) high UPR and low insulin gene expression. The latter state promotes cell proliferation; UPR appears to mediate recovery from ER stress due to high insulin production.
Data confirm that cord blood levels of ghrelin, leptin, and insulin of term newborns correlate with anthropometric parameters at birth (birth weight, head circumference, etc.).
Glucose-dependent de-SUMOylation of tomosyn1 at K298 releases syntaxin1A and controls the amplification of exocytosis in concert with a recently-identified tomosyn1-interacting partner; the Ca(2+)-binding protein secretagogin, which dissociates from tomosyn1 in response to Ca(2+)-raising stimuli and is required for insulin granule trafficking and exocytosis downstream of Ca(2+) influx.
results indicate that higher cerebrospinal fluid insulin levels are related to impairment in cognitive performance and biomarkers of Alzheimer's disease among women and non-carriers of the APOE varepsilon4 allele
single-particle cryo-electron microscopy reconstructions of the 1:2 (4.3 A) and 1:1 (7.4 A) complexes of the insulin receptor ECD dimer with insulin
We expect that these insulin-deficient pigs can be used in diabetes research to test the efficacy and safety of new drugs and the recipient of islet transplantation to investigate optimal transplantation strategies.
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 activity and SFK signaling.
PTPLAD1 and AMPK are rapidly compartmentalized within the plasma membrane (PM) and Golgi/endosome fractions after insulin stimulation and that ATIC later accumulates in the Golgi/endosome fraction.
Pdx-1, MafA and NeuroD1 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 and insulin at a transcriptional level and, their effects on the adipogenic transcription factor PPARgamma, 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 levels are less easily modified.
insulin increased GCLc promoter activity, which required a prerequisite increase or decrease in medium glucose
SOCS3 is an important negative regulator of insulin signaling in porcine adipocytes.
Plasma concentrations of insulin in pigs fed once per day were lower before feeding than after the meal. Plasma concentrations of insulin in ad libitum fed pigs exhibited random fluctuations.
Data show that an expression cassette containing 1500bp of the porcine insulin promoter 5' UTR confers robust and specific transgene expression to beta-cells in vitro and in transgenic mice.
Neutron diffraction data for T(6) porcine insulin were collected to 2.1 A resolution from a single crystal partly deuterated by exchange of mother liquor.
computational analysis of the altered ionization of the B13 Glu in insulin B9 and B10 mutants of 4INS
Results describe the in vitro folding/unfolding of insulin/single-chain insulin.
A two-stage in vitro folding pathway of insulin is proposed, with six major folding intermediates captured during the folding process.
Streptozotocin is able to impair in vitro neonatal pancreatic beta cell insulin release whereas human cytokines is not.
A16Leu had much more significant effects on the foldability of insulin than B17Leu.
The structural dynamics of insulin hexamer dissociation were studied by the photoinduced temperature jump technique and monitored by time-resolved X-ray scattering. The process of hexamer dissociation was found to involve several transient intermediates, including an expanded hexamer and an unstable tetramer.
Insulin signaling role in skeletal muscle atrophy and autophagy in in transition and postpartum period
Structural changes consistent with protein partitioning to the membrane interior and adsorption to a gel phase model lipid bilayer were observed under conditions where the native fold of the protein is significantly destabilised.
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-NPY 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+) 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 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-induced activation of phosphoinositide 3-kinase~mammalian target of rapamycin pathway up-regulates tau protein via acceleration of protein synthesis in adrenal chromaffin cells, promoting neurite-like process outgrowth.
normal and reversed supramolecular chirality of insulin fibrils
Structural changes of insulin crystals in sequential dehydration process.
The structure of insulin fibrils was characterized by deep ultraviolet resonance Raman (DUVRR) and Nuclear Magnetic Resonance (NMR) spectroscopy combined with hydrogen-deuterium exchange.
The gas-phase basicity of the peptide charge state and ligand drive the type of complexes bovine insulin forms with various amino sugars, irrespective of their structural differences.
Exogenous recombinant bovine somatotropin did not affect plasma concentrations of IGF-I and insulin, however, it did improve post-thaw sperm membrane integrity.
Tyrosine, phenylalanine, and cysteine in glycated insulin were the main residues for oxidative modifications.
DEPP is a novel insulin-regulatory molecule expressed abundantly in insulin-sensitive tissues including white adipose tissue and liver.
insulin supports early initiation of the mesodermal factor Brachyury and the signalling molecules Wnt3a and Wnt4 as well as the progression of mesoderm formation
Data show that type 1 diabetic blastocyst did not express insulin mRNA.
Data show that adaptive alpha-cell identity changes are constrained by intra-islet insulin- and Smoothened-mediated signalling, among others.
IRE1alpha-XBP1 pathway plays an important role in the efficient folding of proinsulin and transcriptional induction of the five PDI family proteins, which are critical for correct disulfide bond formation of proinsulin, in pancreatic beta cells.
High INS2 expression is associated with weight gain and obesity.
Data (including data from studies in knockout mice) suggest that Ins2 is involved in impaired nociception/diabetic neuropathy; here, mice heterozygous for mutant Ins2 exhibit (a) significant loss of intra-epidermal nerve fibers, (b) markedly reduced responsiveness to heat in dorsal root ganglion neurons, and (c) mostly unchanged function of cold-sensitive neurons; such mice become diabetic soon after weaning.
In the present study, the mRNA expression of the two mouse insulin genes Ins1 and Ins2 was investigated in MIN6 cells treated with different concentrations of melatonin, and insulin secretion was detected under the same conditions. Following the overexpression or silencing of MTNR1B, the activities of components of the MAPK signaling pathway
These results suggest that PABP interacts with HuD in basal glucose conditions making translation inhibitory complex, however upon glucose stimulation this association is affected and PABP is acted upon by PDI resulting in stimulation of insulin translation.
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) 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.
Data indicate that insulin/incomplete Freund's adjuvant (IFA) does not prevent but induces diabetes in RIP-CD80GP transgenic mice.
RORalpha is a transcriptional activator of insulin.
Mice deficient in coinhibitory PD-L1 or PD-1 molecules (PD-L1(-/-) and PD-1(-/-) mice), were used to study induction of preproinsulin (ppins)-specific CD8 T-cell responses and experimental autoimmune diabetes.
Data suggest that CD34 may be a specific marker for functionality, with some specificity for insulin.
sing glucose as a disease-relevant readout, we screened 2233 molecules and identified three that consistently reduced glucose levels in insulin mutants. Most significantly, we uncovered an insulin-independent beneficial role for androgen receptor antagonism in hyperglycemia, mostly by reducing fasting glucose levels.
Temporal and spatial expression of two insulin genes (insa and insab) during early developmental stages.
These findings suggest that GHRL regulates INS synthesis by mediating its action on growth hormone secretagogue-receptor in the central nervous system and partly involved in carbohydrate-glycogen 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.