Comparative Binding of Beef and Human Insulin to Insulin Antibodies Produced in Man and Guinea Pigs*

Grodsky, Gerold M.; Forsham, Peter H.

doi:10.1172/jci104313

Cited by 28 publications

(10 citation statements)

References 7 publications

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“…The measurement of human insulin, primarily dependent upon the complete recovery of beef insulin, is reliable at most concentrations of human insulin, but accuracy may be impaired in a mixture combining a very low human insulin content with a high beef insulin concentration. It has been suggested that differences and similarities in the binding of various animal insulins with antibodies in human antibeef-pork insulin sera may be due to differences in the amino acid sequence of residues 8 to 10 of the A-chain (4 (19), in contrast to the 25-to 100-fold differences described by Berson and Yalow (4,6 It has been suggested that in vitro biological methods cannot be used to measure arteriovenous differences in insulin-like activity. The insulinlike activity of the blood in the venous drainage to the pancreas, measured by the rat diaphragm or the rat adipose tissue method, is less than that in simultaneously sampled arterial blood; and oxygenation of blood either in the lungs or in vitro can lead to a rise in the biologically estimated insulin-like activity (10,11).…”

Section: Discussionmentioning

confidence: 99%

Studies on Tissue Uptake of Insulin in Man Using a Differential Immunoassay for Endogenous and Exogenous Insulin*

Samols¹,

Ryder²

1961

J. Clin. Invest.

136

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Section: Discussionmentioning

confidence: 99%

Studies on Tissue Uptake of Insulin in Man Using a Differential Immunoassay for Endogenous and Exogenous Insulin*

Samols¹,

Ryder²

1961

J. Clin. Invest.

136

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“…Plasma, promptly separated in a refrigerated centrifuge, was immediately frozen in acetone-dry ice. Disappearance of immunoprecipitable radioactivity from plasma was determined the following day by the method of Grodsky and Forsham (4,5), in which plasma is reacted with guinea pig anti-insulin antibody and the resultant antigen-antibody complex precipitated with 25%o sodium sulfate. This method was modified by omitting the initial acid-alcohol extraction and by carrying out the reaction in the presence of excess anti-insulin 1Bovine-insulin-'"I, approximately 4 mc/mg, Abbott Laboratory, North Chicago, Ill.…”

Section: Methodsmentioning

confidence: 99%

Derivation of a three compartment model describing disappearance of plasma insulin-131I in man

Silvers¹,

Swenson²,

Farquhar³

et al. 1969

J. Clin. Invest.

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Veterans Administration Hospital, Palo Alto, California 94305 AB S T R A C T Insulin-LuI was administered intravenously to normal subjects, to patients with maturityonset diabetes and normal renal function, and to nondiabetic patients with renal failure. The ensuing plasma disappearance curves of immunoprecipitable radioactive insulin were determined, and these data were analyzed in a variety of ways. Firstly, fractional irreversible loss rates of insulin from plasma were calculated and found to be greatly diminished in patients with renal failure (t4 = 39 min), as compared with normal (t4 = 15 min) and diabetic subjects (ti = 12 min). Secondly, plasma insulin-2'I disappearance curves were resolved into sums of three exponentials by the method of "peeling," and values for the resultant three slopes and half-lives were determined. Patients with normal renal function had similar values for all parameters, while those patients with renal failure were differentiated on the basis of the slope of the last component, with a prolongation of its half-life to 275 min (approximately twice normal). Finally, a three pool model was formulated to describe the kinetics of plasma insulin disappearance in man. representing plasma (pool 1), interstitial fluid (pool 2), and all tissues in which insulin is utilized and degraded (pool 3). The proposed model adequately describing the disappearance curves of insulin-'I observed in all patients indicated that volumes (per cent body weight) of pool 1 (4.04) and pool 2 (10.11), calculated on the basis of the model and the experimental data, corresponded closely to estimates of plasma and interstitial fluid vol- umes obtained by independent means. It also demonstrated that patients with renal failure were characterized by a decreased removal rate of insulin from pool 3 and an increased recycling rate of insulin from pool 3 to pool 2. It is concluded that the proposed model represents a reasonable description of the kinetics of insulin distribution and degradation, and that its use provides quantitative insights into the physiology of insulin metabolism.

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“…Plasma glucose was measured by means of a Technicon AutoAnalyzer (11). Disappearance of immunoprecipitable radioactivity from plasma was determined by the method of Grodsky and Forsham (12,13) in which plasma is reacted with guinea pig anti-insulin antibody and the resultant antigen-antibody complex precipitated with 25% sodium sulfate. This method was modified by omitting the initial acid alcohol extraction and by carrying out the reaction in the presence of excess anti-insulin antibody.…”

mentioning

confidence: 99%

“…Fur-thermore, insulin specific activity time curves are curvilinear when graphed on semilog paper (2)(3)(4)(5)(6)(7) indicating that a multicompartmental system exists for insulin degradation. Nevertheless, in none of these studies has insulin (12,13) in which plasma is reacted with guinea pig anti-insulin antibody and the resultant antigen-antibody complex precipitated with 25% sodium sulfate. This method was modified by omitting the initial acid alcohol extraction and by carrying out the reaction in the presence of excess anti-insulin antibody.…”

mentioning

confidence: 99%

Insulin delivery rate into plasma in normal and diabetic subjects

Stern¹,

Farquhar²,

Silvers³

et al. 1968

J. Clin. Invest.

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A B S T R A C T Removal of insulin-1'3I from plasma was studied in normal and diabetic subjects with both single injection and continuous infusion of isotope techniques. Patients were studied either in the fasting state or during steady-state hyperglycemia produced by a continuous intravenous glucose infusion. Steady-state plasma insulin concentration during these studies ranged from 10 to 264 JuU/ml. Labeled insulin specific activity time curves consisted of more than one exponential, indicating that a multicompartmental system for insulin metabolism exists. A mathematical technique which is applicable to non-first order processes was used to calculate the rate at which insulin was lost irreversibly from the plasma insulin pool. A direct, linear relationship was found between insulin irreversible loss rate and plasma insulin concentration over the range of concentrations studied. This linearity implies lack of saturability of the insulin removal mechanism. Since the plasma insulin pool was in a steady state during these studies, insulin irreversible loss rate was equal to the rate at which newly secreted insulin was being delivered to the general circulation. Therefore, these results indicate that changes in plasma insulin concentration result from parallel INTRODUCTIONDevelopment of a precise immunoassay for the measurement of plasma insulin concentration (1) has greatly facilitated study of carbohydrate and insulin metabolism. Interpretation of plasma insulin measurements has generally rested on the belief that changes in concentration are direct reflections of parallel changes in pancreatic insulin secretion rate. However, there is little experimental evidence in support of this assumption. Because insulin is secreted into the portal vein, and not into the systemic circulation, determination of pancreatic insulin secretion rate in intact subjects presents formidable difficulties. In contrast, plasma insulin removal rate, which in the steady state is equal to the rate of delivery of insulin into the systemic circulation, can be determined by standard isotopic techniques, and many such studies have been published (2-8). Unfortunately these studies suffer from a variety of defects. In some cases (3-7) disappearance of nonspecific proteinprecipitable radioactivity has been followed despite the fact that Berson, Yalow, Bauman, Rothschild, and Newerly (2), and subsequently others (9,10) In three patients (G.B., W.K., and E.D.), continuous infusions of insulin-'I were given by means of a constant infusion pump. In each of these studies, the continuous infusion of isotope was preceded by a primer dose. The infusion rates were: G.B., 170,686 cpm/min; W.K., 135,240 cpm/min; and E.D., 71,439 cpm/min.Primer doses were in each instance equal to 10 times the per minute infusion rate. Venous blood samples were obtained at i hr intervals for 4 hr. Only those samples obtained after isotopic steady state had been achieved were used in the subsequent calculations.Technical procedures. Blood was drawn into tubes containing e...

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Comparative Binding of Beef and Human Insulin to Insulin Antibodies Produced in Man and Guinea Pigs*

Cited by 28 publications

References 7 publications

Studies on Tissue Uptake of Insulin in Man Using a Differential Immunoassay for Endogenous and Exogenous Insulin*

Studies on Tissue Uptake of Insulin in Man Using a Differential Immunoassay for Endogenous and Exogenous Insulin*

Derivation of a three compartment model describing disappearance of plasma insulin-131I in man

Insulin delivery rate into plasma in normal and diabetic subjects

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