Oxidative Stress, β-Cell Apoptosis, and Decreased Insulin Secretory Capacity in Mouse Models of Hemochromatosis

Cooksey, Robert C.; Jouihan, Hani; Ajioka, Richard S.; Hazel, Mark W.; Jones, Deborah L.; Kushner, James P.; McClain, Donald A.

doi:10.1210/en.2004-0392

Cited by 236 publications

(213 citation statements)

References 29 publications

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“…The study of mouse models of haemochromatosis also suggests that iron overload and not the HFE mutations per se are responsible for the glucose homeostasis phenotype [15], and the heterozygous controls in this study did not have elevated serum ferritin concentrations. Further support for the primary role of iron in the pathogenesis of haemochromatosis-associated diabetes is found in reports that even in the absence of HFE mutations individuals with diabetes have higher than average iron indices [38][39][40].…”

Section: Discussionmentioning

confidence: 52%

“…Our studies of mouse models of haemochromatosis revealed that beta cell mass is decreased secondary to apoptosis [15]. This is likely to be the case in humans as well, since at the stage of IGT the AIRg was significantly decreased.…”

Section: Discussionmentioning

confidence: 52%

“…This is likely to be the case in humans as well, since at the stage of IGT the AIRg was significantly decreased. In the mouse models, the decreased insulin secretory capacity is compensated for by increased Si, such that NGT or supranormal glucose tolerance is maintained [15]. Similarly in the humans with haemochromatosis, there was no evidence for insulin resistance in these individuals, and conversely, there was a trend toward an increase in Si in all of the data (FSIVGTT, QUICKI and clamp), although the Si did not increase significantly.…”

Section: Discussionmentioning

confidence: 87%

“…The overall prevalence of abnormal fasting glucose values in this group were: IFG 13% (95% CI [8][9][10][11][12][13][14][15][16][17][18][19][20]; diabetes 26% (95% CI 20-34). Thirty-two of the males (31%) and four of the females (12%) had diabetes.…”

Section: Historical Review Of Diabetes Prevalence Data In Haemochromamentioning

confidence: 99%

“…We have recently described mouse models of haemochromatosis, namely mice with targeted deletion of Hfe or replacement of deleted wild-type Hfe with the cognate human mutation C282Y [15]. These mice exhibited decreased insulin secretory capacity secondary to oxidative stress, decreased glucose-stimulated insulin secretion, and beta cell apoptosis.…”

Section: Introductionmentioning

confidence: 99%

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High prevalence of abnormal glucose homeostasis secondary to decreased insulin secretion in individuals with hereditary haemochromatosis

et al. 2006

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Aims/hypothesis: The prevalence and mechanisms of diabetes in hereditary haemochromatosis are not known. We therefore measured glucose tolerance, insulin secretory capacity and insulin sensitivity in adults with haemochromatosis.Subjects and methods: Subjects recruited from referrals to a haemochromatosis clinic underwent OGTT and frequently sampled IVGTT. A chart review of former clinic patients was also performed. Results: The prevalence of diabetes (23%) and IGT (30%) was increased in haemochromatosis compared with matched control subjects (0% diabetes and 14% IGT). Subjects with haemochromatosis and diabetes were overweight (14%) or obese (86%). The prevalence of diabetes, as determined by chart review of fasting glucose values, in subjects who had haemochromatosis and were in the 40-79 years age range was 26%. Overall, patients with haemochromatosis and control subjects had similar values for acute insulin response to glucose and insulin sensitivity. However, patients with haemochromatosis and IGT had a 68% decrease in acute insulin response to glucose (p<0.02) compared with those with NGT. They were not insulin-resistant, exhibiting instead a 62% increase in insulin sensitivity (NS). Haemochromatosis subjects with diabetes exhibited further declines in acute insulin response to glucose, insulin resistance, or both.Conclusions/interpretation: Diabetes and IGT are common in haemochromatosis, justifying screening for diabetes and therapeutic phlebotomy. The major abnormality associated with IGT is decreased insulin secretory capacity. Diabetes is usually associated with obesity and concomitant insulin resistance.

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 87%

Section: Historical Review Of Diabetes Prevalence Data In Haemochromamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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High prevalence of abnormal glucose homeostasis secondary to decreased insulin secretion in individuals with hereditary haemochromatosis

et al. 2006

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Glucose toxicity

Yki‐Järvinen

McClain

2015

International Textbook of Diabetes Mellitus

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The International Textbook of Diabetes Mellitus has been a successful, well-respected medical textbook for almost 20 years, over 3 editions. Encyclopaedic and international in scope, the textbook covers all aspects of diabetes ensuring a truly multidisciplinary and global approach. Sections covered include epidemiology, diagnosis, pathogenesis, management and complications of diabetes and public health issues worldwide. It incorporates a vast amount of new data regarding the scientific understanding and clinical management of this disease, with each new edition always reflecting the substantial advances in the field. Whereas other diabetes textbooks are primarily clinical with less focus on the basic science behind diabetes, ITDM's primary philosophy has always been to comprehensively cover the basic science of metabolism, linking this closely to the pathophysiology and clinical aspects of the disease.Edited by four world-famous diabetes specialists, the book is divided into 13 sections, each section edited by a section editor of major international prominence. As well as covering all aspects of diabetes, from epidemiology and pathophysiology to the management of the condition and the complications that arise, this fourth edition also includes two new sections on NAFLD, NASH and non-traditional associations with diabetes, and clinical trial evidence in diabetes.This fourth edition of an internationally recognised textbook will once again provide all those involved in diabetes research and development, as well as diabetes specialists with the most comprehensive scientific reference book on diabetes available.

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A computer‐aided educational tool for induction motors

Gençer

Gedikpınar

2012

Comp Applic In Engineering

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ABSTRACT:The computer-aided educational tools have gained popularity in the last years with successful implementation in many areas, including in engineering education. These tools are aimed to help the students for visualization of the concepts and to provide the graphical feedback during the learning process. This paper presents a computer-aided educational tool for induction motors, which is a part of laboratories in the electrical machinery courses. This tool helps to students and educators in subject to teaching/of the equivalent circuit, and the vector/phasor diagrams in induction motors. The tool software was prepared in DELPHI environment. It has flexible structure which is enable to users to change motor label values, and to solve equivalent circuit parameters and winding account. The proposed educational tool was utilized in laboratories of electric machinery courses and well received by students.

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Oxidative Stress, β-Cell Apoptosis, and Decreased Insulin Secretory Capacity in Mouse Models of Hemochromatosis

Cited by 236 publications

References 29 publications

High prevalence of abnormal glucose homeostasis secondary to decreased insulin secretion in individuals with hereditary haemochromatosis

High prevalence of abnormal glucose homeostasis secondary to decreased insulin secretion in individuals with hereditary haemochromatosis

Glucose toxicity

A computer‐aided educational tool for induction motors

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