[
            <sup>123</sup>
            I]Insulin Metabolism in Normal Rats and Humans: External Detection by a Scintillation Camera

Sodoyez, Jean-Claude; Sodoyez-Goffaux, F; Guillaume, Michèle; Merchie, G

doi:10.1126/science.6337399

Cited by 56 publications

(38 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In previous studies, we showed that the most prominent uptake occurred by the liver, which reached a maximum in 3-4 min and was about 30% of the total injected dose. This uptake appears to be receptor-mediated and can be blocked by injection of excess unlabelled insulin [14] or by antibodies to the insulin receptor [18]. Renal uptake represented about 15% of the total injected dose, but did not appear to be receptor mediated, and actually increased when hepatic uptake was blocked by insulin or anti-receptor antibody [14,18].…”

Section: Discussionmentioning

confidence: 99%

“…This uptake appears to be receptor-mediated and can be blocked by injection of excess unlabelled insulin [14] or by antibodies to the insulin receptor [18]. Renal uptake represented about 15% of the total injected dose, but did not appear to be receptor mediated, and actually increased when hepatic uptake was blocked by insulin or anti-receptor antibody [14,18]. In the present study, we have applied this technique to study insulin biokinetics and receptor interaction in the Zucker obese rat.…”

Section: Discussionmentioning

confidence: 99%

“…Insulin binding to isolated soleus muscle has been shown * Present address: Department of Internal Medicine, University of Liege, H6pital de Bavi6re, 66 Boulevard de la Constitution, B-4020 Liege, Belgium to be decreased [9], while that to hepatocytes has been more variable with some studies indicating a decreased binding [10,11] or mildly decreased binding [12] or no change [13], especially when investigations were performed on young rats (10-15-week old). In the present study, we have applied a new technique involving 123I-labelled insulin and scintillation scanning [14] to study insulin kinetics and half-life in vivo in this animal model of obesity and insulin resistance.…”

mentioning

confidence: 99%

See 2 more Smart Citations

In vivo imaging and quantitative analysis of insulin-receptor interaction in lean and obese Zucker rats

Sodoyez¹,

Sodoyez-Goffaux²,

Treves³

et al. 1984

Diabetologia

Self Cite

View full text Add to dashboard Cite

Summary, Imaging and quantitative analysis of insulin-receptor interaction was studied in vivo in lean and obese Zucker rats, using a recently developed technique in which purified Tyr M4 123I-monoiodoinsulin is intravenously injected and the tracer followed by scintillation scanning. The obese rats were 72% overweight, had near normal blood glucose concentrations and an ll-fold increase in plasma insulin concentration. In both groups of rats, the tracer was rapidly taken up by the liver (by a receptor mediated mechanism) and the kidneys (by a non-receptor mediated process). Past this maximum, radioactivity decreased in both organs as 123I-insulin was degraded and free ~z3I-iodide was released into the plasma compartment. Heart radioactivity (i. e. blood pool) mirrored that of the liver and kidneys. The rapid initial decrease of blood radioactivity was concomitant with liver and kidney uptake of 123I-insulin. Release of free iodide from these organs induced a slow secondary rise of blood radioactivity followed by a final decline corresponding to clearance of plasma iodide, mainly by urinary excretion. Liver radioactivity profiles of lean and obese rats were parallel. When expressed per g weight, liver radioactivity was significantly decreased in obese rats. However, due to hepatomegaly in obese rats, total liver radioactivity was significantly higher in homozygous fa/fa rats than in lean littermates. Furthermore, if the marked hyperinsulinaemia of the obese rats is taken into account, total bound insulin was enhanced in the liver of fa/fa rats whatever reference is used, either g weight or total liver. The kidney profile of radioactivity of both rats was not significantly different. In conclusion: (1) obese rats are insulin resistant as near normal glycaemia is achieved at the price of a marked hyperinsulinaemia; (2) liver uptake of insulin is enhanced in obese rats, and (3) the insulin resistance syndrome of fa/fa rats is not due to a decrease in liver insulin receptor number and/or affinity but rather to as yet unknown event(s) subsequent to receptor binding.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

In vivo imaging and quantitative analysis of insulin-receptor interaction in lean and obese Zucker rats

Sodoyez¹,

Sodoyez-Goffaux²,

Treves³

et al. 1984

Diabetologia

Self Cite

View full text Add to dashboard Cite

show abstract

“…12 Insulin metabolism occurs mainly in the liver and, to a much lesser extent, in the kidneys and muscle tissues. The enzyme insulin-glutathione transhydrogense cleaves the intermolecular disulfide bonds holding the A and B chains.…”

Section: Diabetes Management and Anti-diabetic Drugs Classificationmentioning

confidence: 99%

Insulin and Oral Antidiabetic Agents

Mehanna¹

2005

Am J Pharm Educ

View full text Add to dashboard Cite

The current manuscript describes an overview for therapeutic approaches to treat diabetes mellitus. Detailed presentation of the role of insulin in both disease state development and therapy is given. The article also addresses the classification, chemistry, pharmacokinetic properties, dosage forms, mechanisms of action, and therapeutic indications of oral anti-diabetic agents currently available for clinical use. The paper also details the rationale of differences in the onset and duration of action of various insulin preparations. The paper also briefly addresses the phenomena of development of insulin resistance, multi-ingredient dosage form of oral anti-diabetic agents, and approaches to teaching the topic in the classroom.

show abstract

“…3871-3876 , 1995 ) From plasma la bel deca y cu rves and in sulin con centrations , the in-C IRCULATING insulin has, nec essarily, a shor t ha lf-life (1), becau se of its fast respon se to hyp erglycem ic cha l lenges (2), a conseque nce of its funda me n tal ro le in the ma in tenance of gly cemia (3). The insulin resp onse to increases in circulating glucago n (4), ca techo lami nes (5), or amino acids (6)(7)(8) is pr actically immediate.…”

mentioning

confidence: 99%

Rat insulin turnover in vivo.

et al. 1995

View full text Add to dashboard Cite

ABSTRACTsulin pool size, h al f-life, and rate of degr a dation were calculated. Zucker lean and obese rats were injected under pen tob arbit al a n Obese r ats had hi gh er in sulin lev els (2.43 nM) a nd showed less effect esthesia with 125I-labeled insulin ; at timed interval s from 30 to 120 of norad renalin e than th eir lean coun terparts , in wh ich insul in dis sec, blood sa mples wer e ex trac te d and us ed for the estimation of tr ibu t ion volu me shran k wit h nor adr enaline trea tme n t . Th e half-life insulin levels by RIA. A group of r ats fr om each se r ies was ma intained of pla sma ins ulin was sim ila r in all gro u ps (ra nge, 226 -314 sec). P ool under a const a nt infu sion of noradren ali ne. For each insu lin deter size and overall degradation rates were higher in obese (198 fem minatio n, a duplica te blood sa mp le con t aining the sa me a mount of tok atals) th an in lean ra ts (28 ferntok atals ). It is pos tula ted th a t obes e insulin as th at used in th e RIA, bu t withou t the ra dioactive label, was r a ts syn thesize and cleave much more insu lin th a n lean controls used as a bla nk for in sulin measu rem ent. The r a dioactivi ty in t hese despite th eir highe r circulating levels of ins ulio . (Endocrinology 136: tubes was then used for th e mea s uremen tofinsulin lab el per ml blood.3871-3876 , 1995 ) From plasma la bel deca y cu rves and in sulin con centrations , the in-C IRCULATING insulin has, nec essarily, a shor t ha lf-life(1), becau se of its fast respon se to hyp erglycem ic cha l lenges (2), a conseque nce of its funda me n tal ro le in the ma in tenance of gly cemia (3). The insulin resp onse to increases in circulating glucago n (4), ca techo lami nes (5), or amino acids (6-8) is pr actically immediate. The ra te of removal of insulin by the liver is high (9 -11), as is the ability of p eripheral tissues to inac tiva te most of the rema ining circula ting ins ulin (l f), 12, 13). In target tissues, ins ulin is inactiva ted by int er naliza tion afte r in terac tion w ith sp ecific receptors (14). The main insulin-cleaving agen t is ins u lin:glu ta thione tran sh y drogenase (EC 1.8.4.2) (12, 15), probably in ad d ition to other enzym es (16,17). Th e ov era ll capacity of th e ma mmal for insulin remo va l and inac tiva tion is cons id era ble, as is the ability of the en docrine pancreas to release lar ge amounts of insulin on demand. All of these factor s com bine to es tablish a fast insulin turnover, su bject to w ide osci lla tions depending on physiological cond ition and enviro nm en t.Ad equa te knowledge of insulin turnove r may be im po r tant for the study of insu lin resp on ses to di fferent stim uli as well as in the understan ding of the m echanism s involved in the d evelopment of lat e-on set dia be tes, insulin resis ta nce, and obesity, situations in w hic h insulin release and the physiological res ponse to insu lin ar e altered (18 -20) .The di rect esti ma tion of ins ulin turnover is com plex, and only approximat e est im ates ar...

show abstract

[ ¹²³ I]Insulin Metabolism in Normal Rats and Humans: External Detection by a Scintillation Camera

Cited by 56 publications

References 11 publications

In vivo imaging and quantitative analysis of insulin-receptor interaction in lean and obese Zucker rats

In vivo imaging and quantitative analysis of insulin-receptor interaction in lean and obese Zucker rats

Insulin and Oral Antidiabetic Agents

Rat insulin turnover in vivo.

Contact Info

Product

Resources

About

[ 123 I]Insulin Metabolism in Normal Rats and Humans: External Detection by a Scintillation Camera

Cited by 56 publications

References 11 publications

In vivo imaging and quantitative analysis of insulin-receptor interaction in lean and obese Zucker rats

In vivo imaging and quantitative analysis of insulin-receptor interaction in lean and obese Zucker rats

Insulin and Oral Antidiabetic Agents

Rat insulin turnover in vivo.

Contact Info

Product

Resources

About

[ ¹²³ I]Insulin Metabolism in Normal Rats and Humans: External Detection by a Scintillation Camera