Heterogeneity of human liver, muscle, and adipose tissue insulin receptor

Caro, JoséF.; Raju, S; Sinha, Madhur K.; Goldfine, Ira D.; Dohm, G. Lynis

doi:10.1016/0006-291x(88)90567-0

Cited by 29 publications

(13 citation statements)

References 16 publications

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“…Caro et al (1988) obtained a protein yield in adipose tissue similar to that found in this study. The yield range in carp ovaries was approximately the half that obtained in carp skeletal muscle (Pdrrizas et al 1991).…”

Section: Discussionsupporting

confidence: 89%

Insulin and IGF-I receptors and tyrosine kinase activity in carp ovaries: changes with reproductive cycle

Gutiérrez

Parrizas

Carneiro

et al. 1993

Fish Physiol Biochem

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Insulin and insulin-like growth factor I (IGF-I) receptors from carp ovaries were semipurified with wheat germ agglutinin at different moments of the reproductive cycle and their binding characteristics and tyrosine kinase activity were studied. Specific receptors for insulin and IGF-I were found. IGF-I receptors presented higher binding (23.8 ± 1.5%), number of receptors (965 ± 20fm/mg) and affinity (KD 0.24 ± 0.03nM) than those shown for insulin receptors (4.1 ± 1%, 530 ± 85fm/mg and 0.85 ± 0.1nM, respectively). Insulin and IGF-I receptors have a tyrosine kinase activity which is not different from that found in muscle of the same species. Seasonal changes were found in binding, with maximum values for insulin and IGF-I reached at the end of pre-spawning period (June). However, while IGF-I binding was observed in all stages, insulin binding decreased in autumn and disappeared in winter, which suggests a different role for the two peptides in ovarian physiology.

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Section: Discussionsupporting

confidence: 89%

Insulin and IGF-I receptors and tyrosine kinase activity in carp ovaries: changes with reproductive cycle

Gutiérrez

Parrizas

Carneiro

et al. 1993

Fish Physiol Biochem

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“…However, the difference in the hepatic and extrahepatic response to insulin in the diabetic subjects is unlikely to be solely due to slowed equilibration between blood and interstitial insulin concentrations because this presumably would be associated with a delayed rather than a virtually absent response to insulin. Alternatively the discordance between the severity of hepatic and extrahepatic insulin resistance may be due to differences in liver and muscle insulin binding and/or signal transduction (29)(30)(31). Insulin increases glucose uptake in muscle primarily by increasing the translocation of glucose transporters to the plasma membrane whereas it decreases hepatic glucose release by altering the activity of glycogenolytic and gluconeogenic enzymes (13,32).…”

Section: Discussionmentioning

confidence: 99%

Assessment of insulin action and glucose effectiveness in diabetic and nondiabetic humans.

Alzaid¹,

Dinneen²,

Turk³

et al. 1994

J. Clin. Invest.

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Insulin concentrations in humans continuously change and typically increase only when glucose also increases such as with eating. In this setting, it is not known whether the severity of hepatic and extrahepatic insulin resistance is comparable and whether the ability of glucose to regulate its own uptake and release is defective in non-insulin-dependent diabetes mellitus (NIDDM). To address this question, NIDDM and nondiabetic subjects were studied when glucose concentrations were clamped at either 5 mM (euglycemia) or varied so as to mimic the glucose concentrations observed in nondiabetic humans after food ingestion (hyperglycemia). Insulin was infused so as to simulate a "nondiabetic" postprandial profile. During euglycemia, insulin increased glucose disposal in nondiabetic but not diabetic subjects indicating marked extrahepatic resistance. In contrast, insulin-induced suppression of glucose release was only minimally less (P < 0.05) in diabetic than nondiabetic subjects (-1.06±0.09 vs. -1.47±0.21 nmol kg-l per 4 h). Hyperglycemia substantially enhanced disposal in both groups. Glucose effectiveness measured as the magnitude of enhancement of disposal (0.59±0.18 vs. 0.62±0.17 nmol kg-l per 4 h) and suppression of release (-0.36±0.12 vs. -0.14±0.12 nmol kg-l per 4 h) did not differ in the diabetic and nondiabetic subjects. In conclusion, when assessed in the presence of a physiological insulin profile, people with NIDDM demonstrate: (a) profound extrahepatic insulin resistance, (b) modest hepatic insulin resistance, and (c) normal ability of glucose to stimulate its own uptake and suppress its own release. (J. Clin. Invest. 1994. 94:2341-2348

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“…11), except for the much weaker competition observed with MA-20 in our purified receptor system. Thus, the observed differences may reflect some tissue specificity (e.g., glycosylation), as recently suggested (37), rather than conformational alternations due to receptor purification. These differences, however, do not appear to change the major characteristics of the receptor kinetics.…”

Section: ) Antibodies On 125i-insulin Disso-mentioning

confidence: 99%

Negative and positive site-site interactions, and their modulation by pH, insulin analogs, and monoclonal antibodies, are preserved in the purified insulin receptor.

Wang

Goldfine

Fujita‐Yamaguchi

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

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The kinetic properties of the insulin receptor were studied in solution after its purification to homogeneity.Dissociation of "I-labeled insulin at a 1:50 dilution was not first order; unlabeled insulin at physiological concentrations accelerated the dissociation rate with a maximal effect at "17 nM. At higher concentrations, the unlabeled insulin slowed the dissociation rate. Maximal acceleration was seen at pH 8. The purification to homogeneity (1-3) and the cloning and expression (4, 5) of the insulin receptor, as well as the availability of monoclonal antibodies (6-12), have recently provided exciting means to investigate the exact mechanisms underlying the complex kinetics of insulin receptor binding. It is now well established that insulin binding departs markedly from simple reversible mass action kinetics (13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Scatchard plots are curvilinear in most systems studied, and the dissociation is not first order. Furthermore, dissociation of 125I-labeled insulin (125I-insulin) at an "infinite" dilution is accelerated in the presence of unlabeled insulin. These basic findings, as well as the effects of numerous structural modifications of the insulin molecule (16,(18)(19)(20) and more recent studies with monoclonal antibodies (7,8,11,12,22), have led to the view (most explicitly developed in refs. 20 and 22) that the insulin-receptor complex can shift reversibly between at least three interconvertible states by site-site interactions, which depend on the nature of the ligand occupying neighboring sites. We distinguished the initial, "empty" state with an apparent affinity denoted KAE; a lower affinity state, Kf, characterized by a faster dissociation rate constant, induced by increased insulin occupancy-the phenomenon known as "negative cooperativity"-and a higher affinity state, which was denoted "Ksu.r " with a much slower dissociation rate.Although arguments have been raised against the negative cooperativity hypothesis (23-25), no alternative model has been proposed that is as compatible as the three-state model outlined above with a variety of experimental findings using either insulin analogs, monoclonal antibodies, or alterations ofreceptors in clinical states, and with more recent studies of alterations in the dimeric structure of the receptor (see ref. 22 for review). While we believe that the experimental evidence favors the site-site interactions model, it is clear that ultimate proof will have to come from the actual demonstration by crystallographic or other physicochemical methods, of alternative conformations of the purified receptor in various liganded states, or by appropriate changes in receptor structure and kinetics generated by site-directed mutagenesis.As a first step in that direction, we have now characterized in detail the kinetic behavior in solution of the insulin receptor purified to homogeneity from human placenta. One of us previously demonstrated that Scatchard plots of 125I-insulin binding to this purified preparation are curvilinear (1...

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Heterogeneity of human liver, muscle, and adipose tissue insulin receptor

Cited by 29 publications

References 16 publications

Insulin and IGF-I receptors and tyrosine kinase activity in carp ovaries: changes with reproductive cycle

Insulin and IGF-I receptors and tyrosine kinase activity in carp ovaries: changes with reproductive cycle

Assessment of insulin action and glucose effectiveness in diabetic and nondiabetic humans.

Negative and positive site-site interactions, and their modulation by pH, insulin analogs, and monoclonal antibodies, are preserved in the purified insulin receptor.

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