Association of polymorphisms in the insulin-degrading enzyme gene with type 2 diabetes in the Korean population

Kwak, Soo Heon; Cho, Y.M.; Moon, Min Kyong; Kim, J.H.; Park, B.L.; Cheong, Hyun Sub; Shin, Hyoung Doo; Jang, Hak Chul; Kim, S.Y.; Lee, H.K.; Park, K.S.

doi:10.1016/j.diabres.2007.08.017

Cited by 26 publications

(19 citation statements)

References 17 publications

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“…Insulin clearance and IDE expression are reduced in type 2 diabetic individuals (Butterfield 1970, Groves et al 2003, Karamohamed et al 2003, Kotronen et al 2007, Kwak et al 2008, Slominskiȋ et al 2009) and in obese and diabetic rodents (McCarroll & Buchanan 1973, Rabkin et al 1986, Strömblad & Björntorp 1986, Kotronen et al 2008, Matveyenko et al 2008, Rezende et al 2012. Also, as previously mentioned, changes in insulin clearance are probably more relevant than the increase in insulin secretion to the higher insulinemia observed in obese individuals ( Erdmann et al 2008Erdmann et al , 2009 and are highly heritable (Guo et al 2012) with the highest correlation with insulinemia (Goodarzi et al 2011).…”

Section: Discussionmentioning

confidence: 67%

Cafeteria diet inhibits insulin clearance by reduced insulin-degrading enzyme expression and mRNA splicing

Brandimarti¹,

Costa-Júnior²,

Ferreira³

et al. 2013

Journal of Endocrinology

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Insulin clearance plays a major role in glucose homeostasis and insulin sensitivity in physiological and/or pathological conditions, such as obesity-induced type 2 diabetes as well as diet-induced obesity. The aim of the present work was to evaluate cafeteria diet-induced obesity-induced changes in insulin clearance and to explain the mechanisms underlying these possible changes. Female Swiss mice were fed either a standard chow diet (CTL) or a cafeteria diet (CAF) for 8 weeks, after which we performed glucose tolerance tests, insulin tolerance tests, insulin dynamics, and insulin clearance tests. We then isolated pancreatic islets for ex vivo glucose-stimulated insulin secretion as well as liver, gastrocnemius, visceral adipose tissue, and hypothalamus for subsequent protein analysis by western blot and determination of mRNA levels by real-time RT-PCR. The cafeteria diet induced insulin resistance, glucose intolerance, and increased insulin secretion and total insulin content. More importantly, mice that were fed a cafeteria diet demonstrated reduced insulin clearance and decay rate as well as reduced insulin-degrading enzyme (IDE) protein and mRNA levels in liver and skeletal muscle compared with the control animals. Furthermore, the cafeteria diet reduced IDE expression and alternative splicing in the liver and skeletal muscle of mice. In conclusion, a cafeteria diet impairs glucose homeostasis by reducing insulin sensitivity, but it also reduces insulin clearance by reducing IDE expression and alternative splicing in mouse liver; however, whether this mechanism contributes to the glucose intolerance or helps to ameliorate it remains unclear.

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Section: Discussionmentioning

confidence: 67%

Cafeteria diet inhibits insulin clearance by reduced insulin-degrading enzyme expression and mRNA splicing

Brandimarti¹,

Costa-Júnior²,

Ferreira³

et al. 2013

Journal of Endocrinology

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“…Evidence for a putative influence of IDE on the pathogenesis of type 2 diabetes was confirmed in association studies in several independent human populations [15][16][17] and in a recently published meta-analysis [18].…”

Section: Introductionmentioning

confidence: 78%

Glucose inhibits the insulin-induced activation of the insulin-degrading enzyme in HepG2 cells

et al. 2009

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Aims/hypothesis Hepatic insulin degradation decreases in type 2 diabetes. Insulin-degrading enzyme (IDE) plays a key role in insulin degradation and its gene is located in a diabetes-associated chromosomal region. We hypothesised that IDE may be regulated by insulin and/or glucose in a liver cell model. To validate the observed regulation of IDE in vivo, we analysed biopsies of human adipose tissue during different clamp experiments in men. Methods Human hepatoma HepG2 cells were incubated in normal (1 g/l) or high (4.5 g/l) glucose medium and treated with insulin for 24 h. Catalytic activity, mRNA and protein levels of IDE were assessed. IDE mRNA levels were measured in biopsies of human subcutaneous adipose tissue before and at 240 min of hyperinsulinaemic, euglycaemic and hyperglycaemic clamps. Results In HepG2 cells, insulin increased IDE activity under normal glucose conditions with no change in IDE mRNA or protein levels. Under conditions of high glucose, insulin increased mRNA levels of IDE without changes in IDE activity. Both in normal and high glucose medium, insulin increased levels of the catalytically more active 15a IDE isoform compared with the 15b isoform. In subcutaneous adipose tissue, IDE mRNA levels were not significantly upregulated after euglycaemic or hyperglycaemic clamps. Conclusions/interpretation Insulin increases IDE activity in HepG2 cells in normal but not in high glucose conditions. This disturbance cannot be explained by corresponding alterations in IDE protein levels or IDE splicing. The loss of insulin-induced regulation of IDE activity under hyperglycaemia may contribute to the reduced insulin extraction and peripheral hyperinsulinaemia in type 2 diabetes.

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“…(Cheng, et al, 2011, Luchsinger, et al, 2004) Certain IDE genotypes are related to a higher risk of diabetes (Fakhrai-Rad, et al, 2000, Karamohamed, et al, 2003, Kwak, et al, 2008, Rudovich, et al, 2009), although the contribution of IDE to diabetes is controversial,(Groves, et al, 2003) and other studies have found no relationship. (Florez, et al, 2006, Qin and Jia, 2008).…”

Section: Discussionmentioning

confidence: 99%

Candidate genes for Alzheimer's disease are associated with individual differences in plasma levels of beta amyloid peptides in adults with Down syndrome

Schupf

Lee

Park

et al. 2015

Neurobiology of Aging

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We examined the contribution of candidate genes for Alzheimer’s disease (AD) on Chromosome 21 and other chromosomes to differences in Aβ peptide levels in a cohort of adults with DS, a population at high risk for AD. Participants were 254 non-demented adults with Down syndrome, 30–78 years of age. Genomic DNA was genotyped using an Illumina GoldenGate custom array. We used linear regression to examine differences in levels of Aβ peptides associated with the number of risk alleles, adjusting for age, sex, level of intellectual disability, race/ethnicity and the presence of the APOE ε4 allele. For Aβ42 levels, the strongest gene-wise association was found for a SNP on CAHLM1; for Aβ40 levels the strongest gene-wise associations were found for SNPs in IDE and SOD1, while the strongest gene-wise associations with levels of the Aβ42/Aβ40 ratio were found for SNPs in SORCS1. Broadly classified, variants in these genes may influence APP processing (CALHM1, IDE), vesicular trafficking (SORCS1), and response to oxidative stress (SOD1).

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Association of polymorphisms in the insulin-degrading enzyme gene with type 2 diabetes in the Korean population

Cited by 26 publications

References 17 publications

Cafeteria diet inhibits insulin clearance by reduced insulin-degrading enzyme expression and mRNA splicing

Cafeteria diet inhibits insulin clearance by reduced insulin-degrading enzyme expression and mRNA splicing

Glucose inhibits the insulin-induced activation of the insulin-degrading enzyme in HepG2 cells

Candidate genes for Alzheimer's disease are associated with individual differences in plasma levels of beta amyloid peptides in adults with Down syndrome

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