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Center for Nephrology and Metabolic Disorders
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Insulin

The INS gene encodes proinsulin which by cleavage of the precursor signal peptide becomes activated. Insulin is an important regulator of glocose homeostasis. Some mutations are associated with autosomal dominant diabetes those include permanent neonatal diabetes and MODY diabetes of type 10. Also, some mutations are associated with abnormal circulating insulin. Those include hyperproinsulinemia, Wakayama insulin and others.

Genetests:

Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA
Clinic Method Genomic sequencing of the entire coding region
Turnaround 25 days
Specimen type genomic DNA
Clinic Method Multiplex Ligation-Dependent Probe Amplification
Turnaround 25 days
Specimen type genomic DNA

Related Diseases:

MODY10 diabetes
INS
Permanent neonatal diabetes mellitus
ABCC8
Developmental delay, epilepsy, and neonatal diabetes
KCNJ11
GCK
INS
KCNJ11
Phosphoribosylpyrophosphate synthetase superactivity
PRPS1
Wolcott-Rallison syndrome
EIF2AK3
Susceptibility to type 1 diabetes 02
INS

References:

1.

Lomedico P et al. (1979) The structure and evolution of the two nonallelic rat preproinsulin genes.

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2.

Shoelson S et al. (1983) Three mutant insulins in man.

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3.

Kwok SC et al. (1983) Identification of a point mutation in the human insulin gene giving rise to a structurally abnormal insulin (insulin Chicago).

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4.

Haneda M et al. (1983) Studies on mutant human insulin genes: identification and sequence analysis of a gene encoding [SerB24]insulin.

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5.

Lebo RV et al. (1982) Assigning the polymorphic human insulin gene to the short arm of chromosome 11 by chromosome sorting.

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6.

Rotwein P et al. (1981) Polymorphism in the 5'-flanking region of the human insulin gene and its possible relation to type 2 diabetes.

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7.

Kwok SC et al. (1981) Loss of a restriction endonuclease cleavage site in the gene of a structurally abnormal human insulin.

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8.

Ullrich A et al. (1980) Genetic variation in the human insulin gene.

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9.

Owerbach D et al. (1980) The insulin gene is located on chromosome 11 in humans.

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10.

Bell GI et al. (1980) Sequence of the human insulin gene.

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11.

Bell GI et al. (1979) Nucleotide sequence of a cDNA clone encoding human preproinsulin.

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12.

Lebo RV et al. (1983) Recombination within and between the human insulin and beta-globin gene loci.

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13.

Shibasaki Y et al. (1985) Posttranslational cleavage of proinsulin is blocked by a point mutation in familial hyperproinsulinemia.

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14.

Steiner DF et al. (1985) Structure and evolution of the insulin gene.

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15.

Todd S et al. (1985) Genes for insulin I and II, parathyroid hormone, and calcitonin are on rat chromosome 1.

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16.

Chaganti RS et al. (1985) Germ-line chromosomal localization of genes in chromosome 11p linkage: parathyroid hormone, beta-globin, c-Ha-ras-1, and insulin.

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17.

Seino S et al. (1985) Identification of insulin variants in patients with hyperinsulinemia by reversed-phase, high-performance liquid chromatography.

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18.

Tager H et al. (1979) A structurally abnormal insulin causing human diabetes.

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19.

Sakura H et al. (1986) Structurally abnormal insulin in a diabetic patient. Characterization of the mutant insulin A3 (Val----Leu) isolated from the pancreas.

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20.

Meyers DA et al. (1986) Multipoint mapping studies of the beta-globin, insulin, and c-Ha-ras-1 loci on 11p.

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21.

Vinik AI et al. (1986) Familial hyperinsulinemia associated with secretion of an abnormal insulin, and coexistence of insulin resistance in the propositus.

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22.

Nanjo K et al. (1986) Diabetes due to secretion of a structurally abnormal insulin (insulin Wakayama). Clinical and functional characteristics of [LeuA3] insulin.

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23.

Robinson GL et al. (1994) Isolation and characterization of a novel transcription factor that binds to and activates insulin control element-mediated expression.

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24.

Wang J et al. (1999) A mutation in the insulin 2 gene induces diabetes with severe pancreatic beta-cell dysfunction in the Mody mouse.

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25.

Collinet M et al. (1998) Familial hyperproinsulinaemia due to a mutation substituting histidine for arginine at position 65 in proinsulin: identification of the mutation by restriction enzyme mapping.

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26.

Kayo T et al. (1998) Mapping of murine diabetogenic gene mody on chromosome 7 at D7Mit258 and its involvement in pancreatic islet and beta cell development during the perinatal period.

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27.

Warren-Perry MG et al. (1997) A novel point mutation in the insulin gene giving rise to hyperproinsulinemia.

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28.

Yoshioka M et al. (1997) A novel locus, Mody4, distal to D7Mit189 on chromosome 7 determines early-onset NIDDM in nonobese C57BL/6 (Akita) mutant mice.

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29.

Röder ME et al. (1996) Hyperproinsulinemia in a three-generation Caucasian family due to mutant proinsulin (Arg65-His) not associated with imparied glucose tolerance: the contribution of mutant proinsulin to insulin bioactivity.

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30.

Hua QX et al. (1993) Paradoxical structure and function in a mutant human insulin associated with diabetes mellitus.

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31.

Deltour L et al. (1993) Differential expression of the two nonallelic proinsulin genes in the developing mouse embryo.

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32.

Gabbay KH et al. (1976) Familial hyperproinsulinemia. An autosomal dominant defect.

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33.

Davies PO et al. (1994) Genetic reassignment of the insulin-1 (Ins1) gene to distal mouse chromosome 19.

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34.

Ueki K et al. (2006) Total insulin and IGF-I resistance in pancreatic beta cells causes overt diabetes.

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35.

None (1980) The insulinopathies.

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36.

Given BD et al. (1980) Diabetes due to secretion of an abnormal insulin.

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37.

Robbins DC et al. (1981) A human proinsulin variant at arginine 65.

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38.

Harper ME et al. (1981) Localization of the human insulin gene to the distal end of the short arm of chromosome 11.

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39.

Sures I et al. (1980) Nucleotide sequence of human preproinsulin complementary DNA.

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40.

Shoelson S et al. (1983) Identification of a mutant human insulin predicted to contain a serine-for-phenylalanine substitution.

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41.

Gruppuso PA et al. (1984) Familial hyperproinsulinemia due to a proposed defect in conversion of proinsulin to insulin.

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42.

Haneda M et al. (1984) Familial hyperinsulinemia due to a structurally abnormal insulin. Definition of an emerging new clinical syndrome.

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43.

Robbins DC et al. (1984) Biologic and clinical importance of proinsulin.

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44.

Robbins DC et al. (1984) Familial hyperproinsulinemia. Two cohorts secreting indistinguishable type II intermediates of proinsulin conversion.

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45.

Cheung AT et al. (2000) Glucose-dependent insulin release from genetically engineered K cells.

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46.

Meigs JB et al. (2005) The insulin gene variable number tandem repeat and risk of type 2 diabetes in a population-based sample of families and unrelated men and women.

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47.

Rodríguez S et al. (2004) Haplotypic analyses of the IGF2-INS-TH gene cluster in relation to cardiovascular risk traits.

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48.

None (1976) Editorial: Errors in insulin biosynthesis.

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49.

Obici S et al. (2002) Hypothalamic insulin signaling is required for inhibition of glucose production.

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50.

Abney M et al. (2002) Quantitative-trait homozygosity and association mapping and empirical genomewide significance in large, complex pedigrees: fasting serum-insulin level in the Hutterites.

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51.

Ibáñez L et al. (2001) Insulin gene variable number of tandem repeat genotype and the low birth weight, precocious pubarche, and hyperinsulinism sequence.

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52.

Le Stunff C et al. (2001) Paternal transmission of the very common class I INS VNTR alleles predisposes to childhood obesity.

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53.

Osawa H et al. (2001) Systematic search for single nucleotide polymorphisms in the insulin gene: evidence for a high frequency of -23T-->A in Japanese subjects.

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54.

Vafiadis P et al. (2001) Class III alleles of the variable number of tandem repeat insulin polymorphism associated with silencing of thymic insulin predispose to type 1 diabetes.

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55.

Dandona P et al. (2001) Insulin inhibits intranuclear nuclear factor kappaB and stimulates IkappaB in mononuclear cells in obese subjects: evidence for an anti-inflammatory effect?

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56.

Chan SJ et al. (1987) A mutation in the B chain coding region is associated with impaired proinsulin conversion in a family with hyperproinsulinemia.

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57.

Le Stunff C et al. (2000) The insulin gene VNTR is associated with fasting insulin levels and development of juvenile obesity.

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58.

Jaquet D et al. (2000) Insulin resistance early in adulthood in subjects born with intrauterine growth retardation.

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59.

Stead JD et al. (2000) Allele diversity and germline mutation at the insulin minisatellite.

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60.

Molven A et al. (2008) Mutations in the insulin gene can cause MODY and autoantibody-negative type 1 diabetes.

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61.

Jones JM et al. (1992) Localization of insulin-2 (Ins-2) and the obesity mutant tubby (tub) to distinct regions of mouse chromosome 7.

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62.

Colombo C et al. (2008) Seven mutations in the human insulin gene linked to permanent neonatal/infancy-onset diabetes mellitus.

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63.

Polak M et al. (2008) Heterozygous missense mutations in the insulin gene are linked to permanent diabetes appearing in the neonatal period or in early infancy: a report from the French ND (Neonatal Diabetes) Study Group.

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64.

Edghill EL et al. (2008) Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood.

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65.

Støy J et al. (2007) Insulin gene mutations as a cause of permanent neonatal diabetes.

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66.

Farris W et al. (2003) Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo.

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67.

Yano H et al. (1992) A novel point mutation in the human insulin gene giving rise to hyperproinsulinemia (proinsulin Kyoto).

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68.

Haneda M et al. (1986) Low frequency of the large insertion in the human insulin gene in Japanese.

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69.

Selden RF et al. (1987) Regulation of insulin-gene expression. Implications for gene therapy.

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70.

Schwartz GP et al. (1987) A superactive insulin: [B10-aspartic acid]insulin(human).

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71.

Carroll RJ et al. (1988) A mutant human proinsulin is secreted from islets of Langerhans in increased amounts via an unregulated pathway.

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72.

Michalova K et al. (1988) Chromosome localization of the human insulin gene in transgenic mouse lines.

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73.

Williams LG et al. (1985) Allelic variation adjacent to the human insulin and apolipoprotein C-II genes in different ethnic groups.

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74.

Elbein SC et al. (1985) Hyperproinsulinemia in a family with a proposed defect in conversion is linked to the insulin gene.

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75.

White R et al. () Construction of linkage maps with DNA markers for human chromosomes.

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76.

Gabbay KH et al. (1979) Familial hyperproinsulinemia: partial characterization of circulating proinsulin-like material.

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77.

Rotwein P et al. (1986) Genetic analysis of the hypervariable region flanking the human insulin gene.

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78.

Soares MB et al. (1985) RNA-mediated gene duplication: the rat preproinsulin I gene is a functional retroposon.

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79.

Lichter P et al. (1990) High-resolution mapping of human chromosome 11 by in situ hybridization with cosmid clones.

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80.

Barbetti F et al. (1990) Two unrelated patients with familial hyperproinsulinemia due to a mutation substituting histidine for arginine at position 65 in the proinsulin molecule: identification of the mutation by direct sequencing of genomic deoxyribonucleic acid amplified by polymerase chain reaction.

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81.

Frøsig C et al. (2007) Effects of endurance exercise training on insulin signaling in human skeletal muscle: interactions at the level of phosphatidylinositol 3-kinase, Akt, and AS160.

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82.

Awata T et al. (2007) Insulin gene/IDDM2 locus in Japanese type 1 diabetes: contribution of class I alleles and influence of class I subdivision in susceptibility to type 1 diabetes.

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83.

Narendran P et al. (2006) Proinsulin is encoded by an RNA splice variant in human blood myeloid cells.

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84.

Santoro N et al. (2006) Insulin gene variable number of tandem repeats (INS VNTR) genotype and metabolic syndrome in childhood obesity.

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85.

Heude B et al. (2006) The insulin gene variable number of tandem repeat: associations and interactions with childhood body fat mass and insulin secretion in normal children.

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86.

Steiner DF et al. (1967) The biosynthesis of insulin and a probable precursor of insulin by a human islet cell adenoma.

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87.

Olansky L et al. (1992) A variant insulin promoter in non-insulin-dependent diabetes mellitus.

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88.

NCBI article

NCBI 3630 external link
89.

OMIM.ORG article

Omim 176730 external link
90.

Orphanet article

Orphanet ID 168345 external link
91.

Wikipedia article

Wikipedia EN (Insulin) external link
Update: Aug. 14, 2020
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