Insulin degrading enzyme activity and insulin binding of erythrocytes in normal subjects and Type 2 (non-insulin-dependent) diabetic patients

Standl, Eberhard; Kolb, Helmut J.

doi:10.1007/bf00253495

Cited by 19 publications

(10 citation statements)

References 48 publications

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“…Results of analyses of IDE activity in biological fluids (blood cells, plasma, wound fluid, cerebrospinal fluid) of diabetic patients reported in the literature are controversial and apparently depend on a range of factors, including study design, the type of diabetes mellitus and the type of treatment for diabetes. One of the studies showed that IDE activity of erythrocytes was increased in patients with type 2 diabetes taking sulfonylureas, in a subgroup with wellcontrolled type 2 diabetes, and in patients with secondary failure of response to oral therapy, but it was unmodified in well-controlled type 1 diabetic patients [31]. In another study an increase in IDE activity in plasma and erythrocytes was demonstrated both in insulin-dependent and in noninsulin-dependent diabetic patients [32].…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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

et al. 2009

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“…One of the studies showed that IDE activity of erythrocytes was increased in T2DM patients taking sulphonylureas, in a subgroup with well-controlled diabetes, and in patients with secondary failure to oral therapy, but it was unmodified in type 1 diabetic patients in good control (60). In another study, an increase of IDE activity in plasma and erythrocytes was demonstrated both in insulin-dependent and in non-insulin-dependent diabetic patients (61).…”

Section: Compoundmentioning

confidence: 93%

Insulin-degrading enzyme: new therapeutic target for diabetes and Alzheimer’s disease?

et al. 2016

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Insulin-degrading enzyme (IDE) is a major enzyme responsible for insulin degradation. In addition to insulin, IDE degrades many targets including glucagon, atrial natriuretic peptide, and betaamyloid peptide, regulates proteasomal degradation and other cell functions. IDE represents a pathophysiological link between type 2 diabetes (T2DM) and late onset Alzheimer's disease (AD). Potent and selective modulators of IDE activity are potential drugs for therapies of both diseases. Acute treatment with a novel IDE inhibitor was recently tested in a mouse study as a therapeutic approach for the treatment of T2DM. In contrast, effective IDE activators can be used for the AD treatment. However, because of the pleiotropic IDE action, the sustained treatment with systemic IDE modulators should be carefully tested in animal studies. Development of substrate-selective IDE modulators could overcome possible adverse effects of IDE modulators associated with multiplicity of IDE targets. KEY MESSAGESInsulin-degrading enzyme (IDE) represents a pathophysiological link between type 2 diabetes (T2DM) and Alzheimer's disease (AD). Selective modulators of IDE activity are potential drugs for both T2DM and AD treatment. Development of substrate-selective IDE modulators could overcome possible adverse effects of IDE modulators associated with multiplicity of IDE targets. ARTICLE HISTORY

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“…Reduced binding is an indica tion of decreased sensitivity; whether this is a result of a reduced number of receptors or a reduced affinity can be determined. Standl and Kolb [33] measured binding to erythrocytes in normals and a variety of diabetics (Table 5). Type Fs, orally treated II's with good and poor control, insulin-treated Type II's, and insulininsensitive Type II's (those requiring > 80 IU insulin/day) were studied.…”

Section: Insulinmentioning

confidence: 99%

Dietary sugars and carbohydrate metabolism in type II diabetes.

Hallfrisch

1987

Journal of the American College of Nutrition

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Diabetes, the most common metabolic disease, is responsible for the deaths of over 300,000 Americans annually. The incidence of the disease increases with age and since the U.S. population is graying, prevalence is also increasing. Obesity and family history are strong predictors of diabetes. The etiology of Type II diabetes is heterogeneous. The hyperglycemia of Type II diabetes can result from a variety of metabolic defects including impaired beta cell secretion, receptor deficiencies, or abnormal hepatic production or uptake of glucose. Other glucoregulatory hormones such as glucagon, growth hormone, cortisol, thyroid hormones, somatostatin, and gastric inhibitory polypeptide may contribute to the aberrations of carbohydrate metabolism. Environmental factors including stress, diet, and exercise may also contribute to the disease. Since most diabetics are obese, weight loss should be the first priority in improving status. A variety of diet and exercise regimens may help achieve this goal or even improve glucose control without weight loss. Due to the heterogeneity of the disease individualized treatment must be used to improve status of patients with the various metabolic defects of Type II diabetes.

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Insulin degrading enzyme activity and insulin binding of erythrocytes in normal subjects and Type 2 (non-insulin-dependent) diabetic patients

Cited by 19 publications

References 48 publications

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

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

Insulin-degrading enzyme: new therapeutic target for diabetes and Alzheimer’s disease?

Dietary sugars and carbohydrate metabolism in type II diabetes.

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