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.

In-frame exon 2 deletion in insulin receptor RNA in a family with extreme insulin resistance in association with defective insulin binding: a case report

1996 ◽  
Vol 135 (3) ◽  
pp. 357-363 ◽  
Author(s):  
Wolfgang Moritz ◽  
Marianne Böni-Schnetzler ◽  
Wayne Stevens ◽  
E Rudolf Froesch ◽  
James R Levy
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Receptor Binding ◽  
Type A ◽  
Insulin Binding ◽  
Exon 2 ◽  
Receptor Mrna ◽  
Mrna Transcripts ◽  
Extreme Insulin Resistance ◽  
Type A Insulin Resistance

Moritz W, Böni-Schnetzler M, Stevens W, Froesch ER, Levy JR. In-frame exon 2 deletion in insulin receptor RNA in a family with extreme insulin resistance in association with defective insulin binding. Eur J Endocrinol 1996;135:357–63. ISSN 0804–4643 The phenotype and allelic expression of the insulin receptor gene is presented in a family with a patient with type A insulin resistance. Compared to controls, insulin receptor binding in transformed lymphocytes was 100%, 33% and 13% in the father, mother and proband, respectively. Reduced insulin receptor binding co-segregated with altered insulin receptor mRNA expression; the mother and daughter expressed eight insulin receptor mRNA species, including a set of four normal sized and a set of four shorter mRNA transcripts. In the proband the levels of the normal sized mRNA transcripts were suppressed relative to the shorter transcripts. Reverse polymerase chain reaction (PCR) revealed that the shorter transcripts contained an in-frame deletion of exon 2. Sequencing of the entire insulin receptor coding region revealed a paternally inherited A to T substitution in nucleotide 3205, converting isoleucine 996 to phenylalanine. which does not co-segregate with reduced binding. Therefore, we hypothesize that two findings are necessary for the presentation of type A insulin resistance in this patient: an in-frame deletion of the insulin receptor exon 2 that codes for amino acids crucial for insulin binding; and an inhibition of expression of the paternal insulin receptor allele. Marianne Böni-Schnetzler, Division of Endocrinology and Metabolism, Department of Internal Medicine, University Hospital, 8091 Zurich, Switzerland

Insulin binding and action on fat cells from young healthy females and males

1982 ◽  
Vol 243 (2) ◽  
pp. E158-E167 ◽  
Author(s):  
O. Pedersen ◽  
E. Hjollund ◽  
H. O. Lindskov
Keyword(s):  
Glucose Metabolism ◽  
Cell Surface ◽  
Insulin Receptor ◽  
Glucose Transport ◽  
Receptor Binding ◽  
Glucose Utilization ◽  
Insulin Binding ◽  
Fat Cells ◽  
Insulin Receptor Binding ◽  
Rate Limiting

Insulin binding and action were studied in fat cells from the gluteal region of young healthy subjects. Fat cells from females were larger than those of males, had higher insulin receptor binding and higher rates of noninsulin-stimulated and maximally insulin-stimulated rates of methylglucose transport and glucose metabolism when these data were expressed per cell number. However, when insulin binding and insulin effects were expressed per cell surface, which may be physiologically more relevant, no sex differences were found in insulin binding and glucose transport, whereas noninsulin-stimulated and maximally insulin-stimulated glucose metabolism was still significantly increased in female fat cells. The latter indicates postreceptor differences in glucose metabolism between females and males. The insulin concentrations causing half-maximal responses (a measure of the sensitivity to insulin) of glucose transport, glucose metabolism and lipolysis were similar in fat cells from the two sexes, which is consistent with the comparable values of insulin receptor binding when adjusted to cell surface. Studies of rate-determining steps for the glucose utilization of human fat cells showed that glucose transport was not the rate-limiting step at physiological glucose concentrations. Moreover, at physiological glucose levels, glucose metabolism exhibited a decreased maximal insulin responsiveness and an increased insulin sensitivity when compared with glucose metabolism at low glucose concentrations at which glucose transport is rate limiting for the fat cell glucose utilization.

scholarly journals Absence of down-regulation of the insulin receptor by insulin. A possible mechanism of insulin resistance in the rat

1983 ◽  
Vol 210 (2) ◽  
pp. 373-378 ◽  
Author(s):  
A P Walker ◽  
D J Flint
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Culture Medium ◽  
Insulin Receptors ◽  
Insulin Binding ◽  
Recycling Process ◽  
Down Regulation ◽  
Pregnant Rats ◽  
Pregnancy And Lactation ◽  
Dose Dependent

Insulin resistance occurs in rat adipocytes during pregnancy and lactation despite increased or normal insulin binding respectively; this suggests that a post-receptor defect exists. The possibility has been examined that, although insulin binding occurs normally, internalization of insulin or its receptor may be impaired in these states. Insulin produced a dose-dependent reduction in the number of insulin receptors on adipocytes from virgin rats maintained in culture medium, probably due to internalization of the hormone-receptor complex. In contrast, adipocytes from pregnant and lactating rats did not exhibit this ‘down-regulation’ phenomenon. Down regulation was, however, apparent in all groups when the experiments were performed in Tris buffer (where receptor recycling is inhibited), suggesting that in pregnant and lactating rats insulin receptors are rapidly recycled back to the plasma membrane, whereas in virgin rats this recycling process is less effective. Internalization of insulin was also determined by using 125I-labelled insulin. Adipocytes from pregnant and lactating rats appeared to internalize similar amounts of insulin to virgin rats. In the presence of the lysosomal inhibitor chloroquine, adipocytes from pregnant rats internalized more insulin than virgin or lactating rats. These results suggest that adipocytes from pregnant and lactating rats internalize insulin and its receptor normally, whereas intracellular processing of the insulin receptor may differ from that in virgin rats. In addition the rate of lysosomal degradation of insulin may be altered in adipocytes from pregnant rats.

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.

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