ISSN:
1432-0428
Keywords:
Modified insulins
;
isolated fat cells
;
insulin structure-function relationship
;
insulin receptor
;
125I-insulin binding
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary A number of modified insulins were assayed for biological activity (increase in synthesis of lipids from glucose) and binding affinity (inhibition of receptorbinding of125I-insulin) on rat fat cells and the following was found: -1. The modified insulins tested showed the same maximal effect as native insulin. Decrease in biological activity induced by modifications was interpreted as decrease in potency. -2. Removal of 2 amino acids from the amino-terminal end of the B chain caused little or no decrease in potency. Removal of 5 amino acids from the carboxy-terminal end of the B chain caused a decrease in potency to about 17% of that of insulin. Removal of one amino acid (glycine) from the amino-terminal end of the A chain caused a decrease in potency to about 1 %. -3. Substitutions with acetyl or succinyl residues at position Al had a greater effect on the potency than substitution at position B1 or B29. -4. Cross linkage between positions A1 and B29 caused decreases in potency on fat cells to between 2 and 10%. Cross linkage between positions A1 and B1 almost abolished biological activity. −5. 9 of the modified insulins were tested for ability to inhibit binding of125I-insulin to fat cell receptor sites. The decrease in receptor binding affinity induced by chemical modifications was, in all cases, in agreement with the decrease in biological potency.-6. It is concluded that the binding affinity of insulin to the receptor, and therefore the potency, is dependent on (1.) a largely unchanged tertiary structure of the insulin molecule and (2.) free access to the region of the amino-terminal end of the A chain.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01219665
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