Antibodies that impair insulin receptor binding in an unusual diabetic syndrome with severe insulin resistance

Science ◽  
1975 ◽  
Vol 190 (4209) ◽  
pp. 63-65 ◽  
Author(s):  
J. Flier ◽  
C. Kahn ◽  
J. Roth ◽  
R. Bar
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Receptor Binding ◽  
Severe Insulin Resistance ◽  
Insulin Receptor Binding ◽  
Diabetic Syndrome

Suppression of insulin receptor binding by prolonged enteral or parenteral nutrient infusion in the rat: role of gastric inhibitory polypeptide

1989 ◽  
Vol 67 (9) ◽  
pp. 1105-1109 ◽  
Author(s):  
A. R. Baer ◽  
J. Dupré
Keyword(s):  
Insulin Resistance ◽  
Steady State ◽  
Insulin Receptor ◽  
Receptor Binding ◽  
Plasma Insulin ◽  
Gastric Inhibitory Polypeptide ◽  
Insulin Binding ◽  
Down Regulation ◽  
Insulin Receptor Binding ◽  
Nutrient Infusion

In the rat, prolonged enteral or parenteral alimentation with a high-carbohydrate diet results in hyperinsulinemia, which is substantially greater with the parenteral route. Supplementing the parenteral infusate with porcine gastric inhibitory polypeptide (GIP) to approximate plasma immunoreactive GIP levels achieved with enteral feeding further increases steady-state plasma insulin and glucose concentrations, suggesting insulin resistance. We examined the effects of sustained hyperinsulinemia elicited by continuous nutrient infusion on insulin binding to isolated rat adipocytes and the modification of this response by GIP. Compared with a baseline group, both enterally and parenterally alimented groups showed decreased insulin receptor binding affinity. However, despite substantially different steady-state plasma insulin levels, insulin binding was similar with either infusion route. Factors other than plasma insulin concentration alone therefore contribute to insulin receptor down-regulation during prolonged enteral alimentation. Supplementing the parenteral infusate with exogenous GIP resulted in a further reduction in insulin receptor affinity. Thus, adaptation to continuous nutrient infusion is characterized by insulin receptor down-regulation regardless of the route of nutrient delivery. An additional suppression of insulin receptor binding may in part be responsible for the insulin resistance elicited by prolonged exogenous GIP administration.Key words: gastric inhibitory polypeptide, insulin receptor binding, hyperinsulinemia.

Studies on Insulin Resistance and Insulin Receptor Binding in Myotonia Dystrophica*

1979 ◽  
Vol 49 (2) ◽  
pp. 216-222 ◽  
Author(s):  
GERALD J. M. TEVAARWERK ◽  
KENNETH P. STRICKLAND ◽  
CHAO-HSIUNG LIN ◽  
ARTHUR J. HUDSON
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Receptor Binding ◽  
Insulin Receptor Binding ◽  
Myotonia Dystrophica

scholarly journals Rat Strain Differences in Susceptibility to Alcohol-Induced Chronic Liver Injury and Hepatic Insulin Resistance

2010 ◽  
Vol 2010 ◽  
pp. 1-16 ◽  
Author(s):  
Sarah M. DeNucci ◽  
Ming Tong ◽  
Lisa Longato ◽  
Margot Lawton ◽  
Mashiko Setshedi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Injury ◽  
Insulin Receptor ◽  
Inflammatory Cytokines ◽  
Receptor Binding ◽  
Hepatic Insulin Resistance ◽  
Cytokine Activation ◽  
Gapdh Expression ◽  
Insulin Receptor Binding ◽  
Pro Inflammatory Cytokines

The finding of more severe steatohepatitis in alcohol fed Long Evans (LE) compared with Sprague Dawley (SD) and Fisher 344 (FS) rats prompted us to determine whether host factors related to alcohol metabolism, inflammation, and insulin/IGF signaling predict proneness to alcohol-mediated liver injury. Adult FS, SD, and LE rats were fed liquid diets containing 0% or 37% (calories) ethanol for 8 weeks. Among controls, LE rats had significantly higher ALT and reduced GAPDH relative to SD and FS rats. Among ethanol-fed rats, despite similar blood alcohol levels, LE rats had more pronounced steatohepatitis and fibrosis, higher levels of ALT, DNA damage, pro-inflammatory cytokines, ADH, ALDH, catalase, GFAP, desmin, and collagen expression, and reduced insulin receptor binding relative to FS rats. Ethanol-exposed SD rats had intermediate degrees of steatohepatitis, increased ALT, ADH and profibrogenesis gene expression, and suppressed insulin receptor binding and GAPDH expression, while pro-inflammatory cytokines were similarly increased as in LE rats. Ethanol feeding in FS rats only reduced IL-6, ALDH1–3, CYP2E1, and GAPDH expression in liver. In conclusion, susceptibility to chronic steatohepatitis may be driven by factors related to efficiency of ethanol metabolism and degree to which ethanol exposure causes hepatic insulin resistance and cytokine activation.

Reversal of insulin resistance in adipose tissue of non-insulin-dependent diabetics by treatment with diet and sulphonylurea

1985 ◽  
Vol 108 (1) ◽  
pp. 85-90 ◽  
Author(s):  
Jan Bolinder ◽  
Jan Östman ◽  
Peter Arner
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Receptor ◽  
Receptor Binding ◽  
Insulin Action ◽  
Conventional Treatment ◽  
Glucose Oxidation ◽  
Dependent Diabetes Mellitus ◽  
Insulin Receptor Binding ◽  
Insulin Dependent

Abstract. The effect of conventional treatment on insulin action in subcutaneous adipose tissue was studied in 6 patients with non-insulin-dependent diabetes mellitus (NIDDM). Insulin receptor binding and the effect of the hormone on glucose oxidation were determined before and after 6–14 months of treatment with diet plus sulphonylurea. Glycaemic control and in vivo insulin sensitivity were significantly improved by the treatment. Before treatment, the adipocyte insulin receptor binding and the sensitivity to insulin stimulation of adipose tissue glucose oxidation were normal and did not change after treatment. In contrast, the maximum insulin-induced glucose oxidation was markedly decreased before treatment, whereas it was totally normalized after treatment. The conclusion is that insulin resistance in adipose tissue of NIDDM subjects is solely due to post-receptor defects in insulin action. This resistance is completely off-set by conventional treatment with diet plus sulphonylurea.

scholarly journals Localization of the insulin receptor binding sites for the SH2 domain proteins p85, Syp, and GAP.

1994 ◽  
Vol 269 (44) ◽  
pp. 27186-27192
Author(s):  
P A Staubs ◽  
D R Reichart ◽  
A R Saltiel ◽  
K L Milarski ◽  
H Maegawa ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Receptor Binding ◽  
Binding Sites ◽  
Sh2 Domain ◽  
Insulin Receptor Binding

Insulin action and resistance in obesity and noninsulin-dependent type II diabetes mellitus

1982 ◽  
Vol 243 (1) ◽  
pp. E15-E30 ◽  
Author(s):  
J. M. Olefsky ◽  
O. G. Kolterman ◽  
J. A. Scarlett
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Insulin Receptor ◽  
Insulin Action ◽  
Insulin Receptors ◽  
Tissue Level ◽  
Dependent Diabetes Mellitus ◽  
Target Tissue ◽  
Severe Insulin Resistance ◽  
Glucose Clamp Technique

Resistance to the action of insulin can result from a variety of causes, including the formation of abnormal insulin or proinsulin molecules, the presence of circulating antagonists to insulin or the insulin receptor, or defects in insulin action at the target tissue level. Defects of the latter type are characteristic of obesity and of noninsulin-dependent diabetes mellitus. Analysis of the nature of the insulin resistance in those disorders has been investigated in intact subjects with the use of the euglycemic glucose clamp technique, and both insulin receptors and insulin-mediated glucose metabolism have been studied in adipocytes and monocytes from affected individuals. In both conditions, the cause of insulin resistance is heterogeneous. In some, insulin resistance appears to be due to a defect in the insulin receptor, whereas others have a defect both in the receptor and at the postreceptor level. In both groups, more severe insulin resistance is due to the postreceptor lesion and is correctable with appropriate therapy.

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