Impaired insulin secretion in a mouse model of ataxia telangiectasia

Miles, P. D. G.; Treuner, Kai; Latronica, Marc; Olefsky, Jerrold M.; Barlow, Carrolee

doi:10.1152/ajpendo.00259.2006

Cited by 61 publications

(61 citation statements)

References 21 publications

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“…Still, the impairment in females compared to males, was already evident around the age of 6 y, before the expected effect of sex hormones on growth velocity (Figure 2, Table 2). We did not identify any previous reference regarding this issue in humans, but in the atm − / − mice model, females tended to be smaller than male animals (25). This may partially result from absence of the pubertal spurt due to ovarian failure, as shown in this study.…”

Section: Discussionmentioning

confidence: 56%

“…Abnormalities in glucose metabolism progressing with age have also been described in AT patients (4,6,15,17) as well as in atm -/-mice (25). Diabetes mellitus was first described by Schlach et al (16), is characterized by hyperglycemia, hyperinsulinemia, and peripheral insulin resistance, and is rarely associated with glucosuria or ketosis (6,16).…”

Section: Discussionmentioning

confidence: 98%

“…Growth failure is a prominent prenatal and postnatal feature of mutant atm -/-mice (23,24). Accordingly, human AT fibroblast lines, as well as fibroblasts from the atm -/-mice, grow slowly, undergo premature senescence, and have high requirements for growth factors (17,(23)(24)(25). Impaired IGF-I activity may be implicated, as fibroblasts obtained from AT-affected individuals show low levels of IGF-I receptor (IGF-IR) expression and decreased IGF-IR promoter activity (26).…”

Section: Discussionmentioning

confidence: 99%

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Endocrine abnormalities in ataxia telangiectasia: findings from a national cohort

et al. 2016

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Background: Ataxia telangiectasia (AT) is a genetic multisystem disorder, presenting with progressive ataxia, immune deficiency, and propensity toward malignancy. Endocrine abnormalities (growth retardation, reproductive dysfunction, and diabetes) have been described, however detailed information regarding this aspect is lacking. We aimed to characterize endocrine anomalies and growth patterns in a large cohort of AT patients. Methods: Retrospective study comprising all 52 patients (aged 2-26.2 y) followed at a national AT Clinic. Anthropometric and laboratory measurements were extracted from the charts. results: Median height-SDS was already subnormal during infancy, remaining negative throughout follow up to adulthood. Height-SDS was more impaired than weight-SDS up to age 4 y, thereafter weight-SDS steadily decreased, resulting in progressively lower BMI-SDS. IGF-I-SDS was low (−1.53 ± 1.54), but did not correlate with height-SDS. Gonadal failure was present in all 13 females older than 10 y but only in one male. Two patients had diabetes and 10 had dyslipidemia. Vitamin D deficiency was observed in 52.2% of the evaluated patients. conclusion: Our results suggest a primary growth abnormality in AT, rather than secondary to nutritional impairment or disease severity. Sex hormone replacement should be considered for female patients. Vitamin D levels should be followed and supplementation given if needed.

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Endocrine abnormalities in ataxia telangiectasia: findings from a national cohort

et al. 2016

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“…Patients with A-T are at increased risk of aspiration and some may require post-operative ventilatory support. A-T can be associated with impaired insulin secretion, increased risk of insulin resistance, glucose intolerance and type 2 diabetes [62,95,96]. Peri-operative serum glucose control monitoring is important with the instigation of appropriate treatment.…”

Section: Perioperative Management Of a Patient With A-t Undergoing Sumentioning

confidence: 99%

ERS statement on the multidisciplinary respiratory management of ataxia telangiectasia

et al. 2015

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Ataxia telangiectasia (A-T) is a rare, progressive, multisystem disease that has a large number of complex and diverse manifestations which vary with age. Patients with A-T die prematurely with the leading causes of death being respiratory diseases and cancer. Respiratory manifestations include immune dysfunction leading to recurrent upper and lower respiratory infections; aspiration resulting from dysfunctional swallowing due to neurodegenerative deficits; inefficient cough; and interstitial lung disease/pulmonary fibrosis. Malnutrition is a significant comorbidity. The increased radiosensitivity and increased risk of cancer should be borne in mind when requesting radiological investigations. Aggressive proactive monitoring and treatment of these various aspects of lung disease under multidisciplinary expertise in the experience of national multidisciplinary clinics internationally forms the basis of this statement on the management of lung disease in A-T. Neurological management is outwith the scope of this document.

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“…A-T patients display signs of premature aging as well as insulin resistance and lowered insulin receptor affinity (Lavin 2000). Mouse models of ATM deficiency show an age-dependent increase in blood glucose and decrease in insulin sensitivity, consistent with a conserved role of this protein in metabolic function (Miles et al 2007). In an ApoE -/ -mouse model, haploinsufficiency of ATM leads to accelerated atherosclerosis and multiple features of metabolic syndrome relative to the ApoE -/-mouse (Mercer et al 2010).…”

Section: Ataxia Telangiectasiamentioning

confidence: 83%

Relationship Between DNA Damage and Energy Metabolism: Evidence from DNA Repair Deficiency Syndromes

Vose¹,

Mitchell²

2011

DNA Repair and Human Health

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Impaired insulin secretion in a mouse model of ataxia telangiectasia

Abstract: Miles PD, Treuner K, Latronica M, Olefsky JM, Barlow C. Impaired insulin secretion in a mouse model of ataxia telangiectasia.

Cited by 61 publications

References 21 publications

Endocrine abnormalities in ataxia telangiectasia: findings from a national cohort

Endocrine abnormalities in ataxia telangiectasia: findings from a national cohort

ERS statement on the multidisciplinary respiratory management of ataxia telangiectasia

Relationship Between DNA Damage and Energy Metabolism: Evidence from DNA Repair Deficiency Syndromes

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