Disease relevance of INS

• We found no convincing evidence that INS VNTR class genotype was associated with indexes of body size and adult obesity [1].
• These data suggest that INS VNTR class is not an important determinant of size and body weight regulation in middle-aged men and women [1].
• Markers in the neighbouring genes of INS showed only null to modest associations with prostate cancer [2].
• The MaeIII polymorphism in INS was associated with fasting hyperinsulinemia (P=0.045) [3].
• Our results of INS VNTR polymorphism in patients with the onset of diabetes after 35 years of age confirm the association of Class I INS VNTR with autoimmune diabetes and the protective effect of Class III INS VNTR on the insulin secretion in GADA-positive subjects [4].

Psychiatry related information on INS

• Long-term effects of leisure time physical activity on risk of insulin resistance and impaired glucose tolerance, allowing for body weight history, in Danish men [5].
• The localization of TH to the highly polymorphic INS locus provides four new restriction fragment length polymorphisms which should help determine rapidly whether defects in TH are responsible for bipolar affective disorder in the Old Order Amish and other populations [6].
• During the 31-year follow-up survey of this genetically homogeneous birth cohort, IR was assessed by 'Qualitative Insulin Sensitivity Check Index' (QUICKI), and severity of depressive symptoms by 'Hopkins' Symptom Checklist-25' (HSCL-25) [7].
• These polymorphisms were investigated for their possible association with Alzheimer's disease (AD) and for their effect in carriers of an insulin gene (INS) polymorphism [8].
• Associations between alcohol consumption and insulin sensitivity and cardiovascular disease risk factors: the Insulin Resistance and Atherosclerosis Study [9].

High impact information on INS

• These results suggest that increased in utero expression of paternal INS or IGF2 due to the class I INS VNTR allele may predispose offspring to postnatal fat deposition [10].
• Paternal transmission of the very common class I INS VNTR alleles predisposes to childhood obesity [10].
• To determine which genetic factors predispose obese patients to beta-cell dysfunction, and possibly T2D, we studied single-nucleotide polymorphisms (SNPs) in the region of the insulin gene (INS) among 615 obese children [11].
• BACKGROUND: Insulin resistance, a major factor in the pathogenesis of type 2 diabetes mellitus, is due mostly to decreased stimulation of glycogen synthesis in muscle by insulin [12].
• Effect of troglitazone in insulin-treated patients with type II diabetes mellitus. Troglitazone and Exogenous Insulin Study Group [13].

Chemical compound and disease context of INS

• Wild-type mice treated with TNF-alpha developed a pronounced hyperglycemia along the glucose tolerance test, accompanied by an impaired insulin signaling and increased PTP1B activity in muscle [14].
• Based on these data we propose that the activity of islet-innervating capsaicin-sensitive fibers may have a role in the development of reduced insulin secretion in human type 2 diabetes mellitus [15].
• Administration of the Ad/AAV hybrid vectors to streptozotocin-induced diabetic mice reversed hyperglycemia, consistent the differentiation of functional hepatic insulin-secreting cells [16].
• We have recently shown a comparable activity of lower doses of tamoxifen on several surrogate biomarkers of cardiovascular disease and breast cancer, including Insulin-like Growth Factor-I (IGF-I) [17].
• These new findings improve our understanding of insulin resistance in type 1 diabetes mellitus and of the risk/benefit ratio when 17beta-oestradiol and progesterone are used in oral contraceptives or hormone replacement therapy taken by menopausal women with controlled type 1 diabetes mellitus [18].

Biological context of INS

• The insulin minisatellite (INS VNTR) associates with susceptibility to a variety of diseases [19].
• One is equivalent to the mouse Igf2-P0 transcript, whereas the two others (INSIGF long and short) originate from the upstream INS gene that alternatively splices to downstream IGF2 exons [20].
• The relevance of the insulin gene (INS) variable number tandem repeat (VNTR) polymorphism to indexes of body size and adult obesity is inconclusive [1].
• These results indicate that -23HphI and IVS-69 are the most important INS variants affecting pre-mRNA splicing and suggest that -23HphI+/- is a common functional single nucleotide polymorphism at IDDM2 [21].
• We show that IVS1-6A/T (-23HphI+/-) is a key INS variant that influences alternative splicing of intron 1 through differential recognition of its 3' splice site [21].

Anatomical context of INS

• The insulin gene (INS) is also expressed in human thymus, an ectopic expression site likely involved in immune tolerance [22].
• The co-existence of IGF-2-immunoreactivity and INS-immunoreactivity in the human, rat, and dog endocrine pancreas indicates that mammalian IGF-2 and INS genes are regulated simultaneously [23].
• This thymus-specific defect in Igf2 expression may explain both the absence of central tolerance to INS-secreting beta cells and the lymphopenia (including lack of regulatory RT6(+) T cells) in diabetes-prone BB rats [24].
• In this study, we have assessed the role of PTP1B in the insulin sensitivity of skeletal muscle under physiological and insulin-resistant conditions [14].
• Peroxisome Proliferator-Activated Receptor {alpha} Improves Pancreatic Adaptation to Insulin Resistance in Obese Mice and Reduces Lipotoxicity in Human Islets [25].

Associations of INS with chemical compounds

• Serum insulin (INS) levels were studied following an oral glucose load [26].
• A variable number of tandem repeats (VNTR) polymorphism at the human INS 5'-flanking region consisting of three distinct allele classes has been shown to influence the tissue-specific expression of INS and the insulin-like growth factor 2 (IGF-2) [27].
• Polymorphism of INS VNTR is associated with glutamic acid decarboxylase antibodies and postprandial C-peptide in patients with onset of diabetes after 35 years of age [4].
• There were no differences (P>0.05) between F and UF horses for the plasma concentrations of CORT (69+/-14 versus 76+/-23mug/dL), INS (7.2+/-3.5 versus 7.1+/-1.8muIU/mL) or GLU (90+/-6 versus 86+/-7mg/dL) [28].
• The system that regulates insulin secretion from beta-cells in the islet of Langerhans has a capsaicin-sensitive inhibitory component [15].
• In response to elevated glucose, pre-mRNA species increased within 60 min, whereas increases in mature mRNA did not occur until 48 h, suggesting that measurement of mature mRNA species does not accurately reflect the acute transcriptional response of the insulin gene to glucose [29].

Physical interactions of INS

• OBJECTIVE: Insulin-like growth factor (IGF-I) and IGF binding protein-3 (IGFBP-3) are GH-dependent and their concentrations have been used in the diagnosis of GH deficiency [30].
• Half-maximal displacement of 125I-labelled somatomedin C binding occurred at an unlabelled somatomedin C concentration of 0.7 nmol/l. Insulin competed with 125I-labelled somatomedin for binding to this receptor, but 150-fold more insulin was required for half-maximal displacement [31].
• The present study was undertaken to evaluate the effects of these nutritional extremes on GH-binding protein (BP) levels and on Insulin-like growth factor-I (IGF-I) receptors on red blood cells (RBC) [32].
• These responses are orchestrated by the insulin pathway and are initiated by the binding of insulin to the insulin receptor, which leads to activation of the receptor's intrinsic tyrosine kinase [33].
• We identify PRAS40 as a raptor-interacting protein that binds to mTORC1 in insulin-deprived cells and whose in vitro interaction with mTORC1 is disrupted by high salt concentrations [34].
• To understand the molecular basis of the recognition and unfolding of insulin by IDE, we determined a 2.6-A resolution insulin-bound IDE structure [35].

Regulatory relationships of INS

• BACKGROUND: Insulin-like growth factor I (IGF-I) stimulates cell proliferation and inhibits apoptosis in the lung and other tissues by interacting with the IGF-I receptor [36].
• METHODS: Insulin hypoglycemia (0.1 IU/kg) was induced in 15 women with RA, 18 men with AS, and healthy controls matched for age, sex and body mass index [37].
• Insulin resistance induced by high glucose and high insulin precedes insulin receptor substrate 1 protein depletion in human adipocytes [38].
• Moreover, after 24 hours, the ability of insulin to activate protein kinase B (ie, the phosphorylated protein kinase B [pPKB]-protein kinase B ratio) was decreased by approximately 50% (P < .05) [38].
• These findings provide strong evidence that alpha1,3-FucT-VII may affect insulin signaling by upregulating the phosphorylation and expression of some signaling molecules involved in the InR-signaling pathway [39].

Other interactions of INS

• BACKGROUND: Insulin-like growth factor-I (IGF-I) is a potent mitogen for normal and neoplastic cells, whereas IGF-binding protein-3 (IGFBP-3) inhibits cell growth in many experimental systems [40].
• Imprinting of IGF2 P0 transcript and novel alternatively spliced INS-IGF2 isoforms show differences between mouse and human [20].
• Outcome measures included changes in PET-measured regional cerebral blood flow (rCBF) and plasma concentrations of GLP-1, glucose, insulin, and free-fatty acids (FFA), elicited by the administration of a satiating amount of a liquid formula meal [41].
• There were weak correlations between insulin resistance and TNF-alpha, interleukin-6, and CRP, but these were not significant after correction for body fat [42].
• Ferritin and transferrin are both predictive of the onset of hyperglycemia in men and women over 3 years: the data from an epidemiological study on the Insulin Resistance Syndrome (DESIR) study [43].

Analytical, diagnostic and therapeutic context of INS

• TNF-alpha infusion decreased whole-body insulin sensitivity, based on in vivo euglycemic clamp studies in chow-fed hamsters [44].
• RESEARCH DESIGN AND METHODS: Among 4,501 subjects from the French Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort, 1,277 subjects (644 men and 633 women) were randomly selected for the analysis of iron biomarkers at baseline and at 3 years [43].
• Capsaicin-sensitive sensory fibers in the islets of Langerhans contribute to defective insulin secretion in Zucker diabetic rat, an animal model for some aspects of human type 2 diabetes [15].
• Relationship of Androgens to Insulin Resistance and Chronic Inflammation in Morbidly Obese Premenopausal Women: Studies before and after Vertical Banded Gastroplasty [45].
• Maturation to endothelium was performed with vascular endothelial growth factor (VEGF), insulin-like growth factor-1 plus 2% fetal calf serum, and confirmed by flow cytometry and tube formation assays on Matrigeltrade mark [46].

References