Insulin receptors of skeletal muscle: Specific insulin binding sites and demonstration of decreased numbers of sites in obese rats

Olefsky, Jerrold M.; Bacon, V. A.; Baur, Sonia

doi:10.1016/0026-0495(76)90048-2

Cited by 87 publications

(22 citation statements)

References 32 publications

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“…As shown in our study, the insulin binding capacity of the receptors in the skeletal muscles of STZ diabetic rats significantly increases due to the increase in receptor number with high and low affinity to the hormone (Table 1). Our data concerning the characteristics of insulin receptor are in agreement with that obtained by the same method in rat skeletal muscles [23,24]. It allows us to conclude that functional disturbance in insulin-competent ACSM should not be ascribed to the decreasing of insulin receptor activity.…”

Section: Experimental Streptozotocin (Stz) Diabetessupporting

confidence: 90%

Functional defects in adenylyl cyclase signaling mechanisms of insulin and relaxin in skeletal muscles of rat with streptozotocin type 1 diabetes

Kuznetsova

Plesneva

et al. 2006

Open Life Sciences

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Functional disturbance in the novel adenylyl cyclase signaling mechanism (ACSM) of insulin and relaxin action in rat streptozotocin (STZ) type I diabetes was studied on the basis of the authors' conception of molecular defects in hormonal signaling systems as the main causes of endocrine diseases. Studying the functional state of molecular components of the ACSM and the mechanism as a whole, the following changes were found in the skeletal muscles of diabetic rats compared with control animals: 1) increase of insulin receptor binding due to an increase in the number of insulin binding sites with high and low affinity; 2) increase of the basal adenylyl cyclase (AC) activity and the reduction of AC-activating effect of non-hormonal agents (guanine nucleotides, sodium fluoride, forskolin); 3) reduction of ACSM response to stimulatory action of insulin and relaxin; 4) decrease of the insulin-activating effect on the key enzymes of carbohydrate metabolism, glycogen synthase and glucose-6-phosphate dehydrogenase. Hence, the functional activity of GTP-binding protein of stimulatory type, AC and their functional coupling are decreased during experimental type 1 diabetes that leads to the impairment of the transduction of insulin and relaxin signals via ACSM.

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Section: Experimental Streptozotocin (Stz) Diabetessupporting

confidence: 90%

Functional defects in adenylyl cyclase signaling mechanisms of insulin and relaxin in skeletal muscles of rat with streptozotocin type 1 diabetes

Kuznetsova

Plesneva

et al. 2006

Open Life Sciences

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“…As previous experiments had shown that the activity of the carnitine transporter decreases with long isolation times [42], a rapid and reliable method for isolation of skeletal muscle plasma membrane vesicles had first to be established. Our method yields membrane vesicles after approximately 6 h, with an enrichment of sarcolemmal marker enzymes and contaminations with mitochondria, sarcoplasmic reticulum or cytosol in the same range as for published, more complicated methods [48,49]. Functional characterization of the vesicles revealed active, sodium-dependent transport of l-alanine and transport of d-glucose, as expected for skeletal muscle plasma membrane preparations [27].…”

Section: Discussionmentioning

confidence: 69%

Characterization of L‐carnitine transport into rat skeletal muscle plasma membrane vesicles

Berardi¹,

Stieger²,

Hagenbuch³

et al. 2000

European Journal of Biochemistry

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Transport of l-carnitine into skeletal muscle was investigated using rat sarcolemmal membrane vesicles. In the presence of an inwardly directed sodium chloride gradient, l-carnitine transport showed a clear overshoot. The uptake of l-carnitine was increased, when vesicles were preloaded with potassium. When sodium was replaced by lithium or cesium, and chloride by nitrate or thiocyanate, transport activities were not different from in the presence of sodium chloride. However, l-carnitine transport was clearly lower in the presence of sulfate or gluconate, suggesting potential-dependent transport. An osmolarity plot revealed a positive slope and a significant intercept, indicating transport of l-carnitine into the vesicle lumen and binding to the vesicle membrane. Displacement experiments revealed that approximately 30% of the l-carnitine associated with the vesicles was bound to the outer and 30% to the inner surface of the vesicle membrane, whereas 40% was unbound inside the vesicle. Saturable transport could be described by Michaelis±Menten kinetics with an apparent K m of 13.1 mm and a V max of 2.1 pmol´(mg protein 21 )´s 21 . l-Carnitine transport could be trans-stimulated by preloading the vesicles with l-carnitine but not with the carnitine precursor butyrobetaine, and was cis-inhibited by l-palmitoylcarnitine, l-isovalerylcarnitine, and glycinebetaine. On comparing carnitine transport into rat kidney brush-border membrane vesicles and OCTN2, a sodium-dependent high-affinity human carnitine transporter, cloned recently from human kidney also expressed in muscle, the K m values are similar but driving forces, pattern of inhibition and stereospecificity are different. This suggests the existence of more than one carnitine carrier in skeletal muscle.

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“…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%

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

Davidson¹,

Kaplan²

1977

J. Clin. Invest.

124

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Insulin receptors of skeletal muscle: Specific insulin binding sites and demonstration of decreased numbers of sites in obese rats

Cited by 87 publications

References 32 publications

Functional defects in adenylyl cyclase signaling mechanisms of insulin and relaxin in skeletal muscles of rat with streptozotocin type 1 diabetes

Functional defects in adenylyl cyclase signaling mechanisms of insulin and relaxin in skeletal muscles of rat with streptozotocin type 1 diabetes

Characterization of L‐carnitine transport into rat skeletal muscle plasma membrane vesicles

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

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