The defect in insulin receptors in obese-hyperglycemic mice: A probable accompaniment of more generalized alterations in membrane glycoproteins

Chang, Kwen‐Jen; Huang, Donna; Cuatrecasas, Pedro

doi:10.1016/0006-291x(75)90359-9

Cited by 64 publications

(20 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies in which elevated insulin levels are associated with decreased hormonal binding under a variety of conditions (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) have suggested that the prevailing insulin concentration may itself modulate the number of insulin receptors (13). The present study supports this postulate.…”

Section: Discussionsupporting

confidence: 84%

“…concentrations in the diabetics were twice as high as those in both the normal controls and patients with pancreatitis. Thus, increased insulin concentrations probably account for the decreased hormonal binding (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) in these patients. However, purified hepatic plasma membranes from Chinese hamsters (35) and rats2 rendered diabetic with streptozotocin bound approximately twice as much insulin as control membranes, a result in close agreement with our data.…”

Section: Discussionmentioning

confidence: 99%

“…A decreased capacity for binding insulin is found in hepatic tissue from the ob/ob mouse (1)(2)(3)(4)(5), the db/db mouse (4,5), the normal rat given either gold thioglucose (4) or glucocorticoids (6,7) or harboring a tumor secreting ACTH (8), and the old obese rat compared to young lean animals (9); in monocytes removed from obese humans (10)(11)(12); in cultured lymphocytes (13,14) incubated in vitro in the presence of insulin; in thymocytes (15) and cardiac muscle (16) from the ob/ob mouse; in skeletal muscle from old obese rats compared to young lean animals (17); in adipose tissue from obese humans (12,18), the ob/ob mouse (19), rats given a short course of glucocorticoids (7), and the old obese rat compared to young lean animals (20). Since high levels of insulin in all of these situations are associated with a decreased capacity for binding the hormone, diminished concentrations of insulin might be expected to enhance insulin binding.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Increased insulin binding by hepatic plasma membranes from diabetic rats: normalization by insulin therapy.

Davidson¹,

Kaplan²

1977

J. Clin. Invest.

124

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Increased insulin binding by hepatic plasma membranes from diabetic rats: normalization by insulin therapy.

Davidson¹,

Kaplan²

1977

J. Clin. Invest.

124

View full text Add to dashboard Cite

“…It also remains to be seen whether the enhancement of insulin receptor concentrations by antidiabetic and other substances is not simply due to an effect on plasma membrane glycoproteins generally. Chang, Huang & Cuatrecasas (1975) proposed that in ob/ob mice there are generalized changes in membrane glycoproteins.…”

Section: Ardf-26 Treatmentmentioning

confidence: 99%

Improved Insulin Receptor Assay: Effects of an Antidiabetic Sulphonylurea on Liver Membrane Insulin Receptors From Obese Hyperglycaemic Mice

Greenstein

1979

British J Pharmacology

View full text Add to dashboard Cite

A simple assay of liver membrane insulin receptors is described, under conditions which apparently stabilized the insulin‐receptor complex. The receptor population was measured in the presence of physiological doses of radioactive hormone under conditions which minimized negative co‐operativity effects. Equilibrium between receptor and hormone was attained in vitro within 60 min of incubation time at 13°C with no apparent loss of binding sites after 3 h of incubation. Liver membranes from lean mice possessed 8.8 times the receptor number per mg membrane protein measured in membranes from obese hyperglycaemic (ob/ob) littermates. After treatment of ob/ob mice with ARDF‐26 (Gliquidon; Boehringer Ingelheim Ltd) the concentration of liver membrane insulin receptors was increased 5 fold.

show abstract

“…Decreased insulin binding in tissues and membrane fractions from the genetically obese (ob/ob) mouse [ 1,4], diabetic db/db mouse [4,5], and obese and diabetic human subjects [6,7] may be due t o down regulation, insulin deficiency, or genetic factors. This defect has been shown to be due to a decrease in the total number of insulin binding sites per cell, per milligram protein or per unit surface area.…”

Section: Abstract: Fibroblasts Diabetic Mice Insulin Deoxy Dglucomentioning

confidence: 98%

Alterations in the responsiveness of diabetic fibroblasts to insulin

Raizada

Fellows

1980

J Supramol Struct

View full text Add to dashboard Cite

Fibroblastic cultures from the skin of nondiabetic and diabetic (db/db) mice have been used to investigate alterations in the biological responses of diabetic cells to insulin. Confluent cultures from the skin of both nondiabetic and diabetic animals possess specific receptors for insulin. Diabetic fibroblasts exhibit only 36% as mich specific binding of insulin as nondiabetic fibroblasts, because of a decrease in the total number of binding sites, without a change in binding affinity. Insulin caused a time- and dose-dependent increase in the rate of 2-deoxy D-glucose (dGlc) uptake and in ornithine decarboxylase (ODC) activity of both nondiabetic and diabetic fibroblasts. In nondiabetic cells, half-maximal increase in dGlc uptake was obtained with 0.3 nM insulin, and a maximum increase of 120% was obtained with 4.1 nM insulin. In contrast, diabetic cultures required 0.8 nM insulin for a half-maximal increase in dGlc uptake, and maximum stimulation with 4.1 nM insulin was only 50% above control levels. With 4-fold higher insulin concentrations, ODC activity of diabetic cells was only 40% that of non-diabetic cells. In nondiabetic cells, doing regulation of insulin receptors by insulin abolished the ability of insulin to stimulate dGlc uptake. These results demonstrate that cells cultured from diabetic animals, which possess a decreased number of insulin receptors, also exhibit decreased stimulated of deoxy D-glucose uptake and ornithine decarboxylase activity by insulin.

show abstract

The defect in insulin receptors in obese-hyperglycemic mice: A probable accompaniment of more generalized alterations in membrane glycoproteins

Cited by 64 publications

References 22 publications

Increased insulin binding by hepatic plasma membranes from diabetic rats: normalization by insulin therapy.

Increased insulin binding by hepatic plasma membranes from diabetic rats: normalization by insulin therapy.

Improved Insulin Receptor Assay: Effects of an Antidiabetic Sulphonylurea on Liver Membrane Insulin Receptors From Obese Hyperglycaemic Mice

Alterations in the responsiveness of diabetic fibroblasts to insulin

Contact Info

Product

Resources

About