Glucagon Antibodies After Long-Term Insulin Treatment in a Diabetic Child

Abstract

224Short Communications 96% of the radioactivity in A could be precipitated by incubation with an excess of rabbit anti-glucagon serum and subsequent addition of ethanoCln a corresponding test without antiserum, 3-4% of the radioactivity was precipitated.The relative amounts of 125 1 in r, MIT and DIT were found to be 2.6, 97.2 and 0.3%, respectively. The corresponding vaiues for a material radioiodinated in the same way as the material applied on the column but only purified by a saltingout procedure, were found to be 1.8,83.9 and 14.3%, respectively (the small amount of 125r found in both cases were probably due to damage sustained during storage). Thus, one effect of the anion exchange chromatography and subsequent selection of the ~-pool was a practically complete rem oval of DIT-containing material.It is concluded that essentially all of the 125 1 in ~ was present as MIT-iodine in immunoreactive 1251-glucagon. We have not investigated how the radioiodine was distributed between the two tyrosines of the glucagon molecule. Different dilutions of A and of another 1251-glucagon (B), prepared by the same iodination procedure but followed only bya crude purification-as described by Heding (1971), were used for making standard curves in the glucagon radioimmunoassay. The two sets of curves did not cross each other at any point. Fig. 1 b shows optimal standard curves for ~ and !! with the same rabbit anti-glucagon serum. It appears that the 1251-glucagon purified by chromatography was better suited for use in the radioimmunoassay than the crudely purified 125I-glucagon. This finding has been reproduced with anti-glucagon sera from different rabbits and with different preparations of each of the two kinds of 12SI-glucagon.The nucleotide metabolism of the organism and the effect of the nucleotides on various metabolie processes are not yet clear. In view of the similarity between the biguanide derivates used with success in some cases of diabetes mellitus and some nucleotides, this problem is again, beginning to arouse interest, and the possibility of naturally occurring guanido compounds in the regulation of carbohydrate and protein metabolism has been propounded (Butterjield, Cox and Whichelow 1968).In a previous paper we demonstrated that adenine and guarIine increase the glucose release of rat Iiver perfused with glucose-Downloaded by: National University of Singapore. Copyrighted material.

Glucagon‐reactive islet‐infiltrating CD8 T cells in NOD mice

“…There are some reports that an immune response to proglucagon may occur in both NOD mice, as shown here, and in T1D patients . Indeed, glucagon‐specific antibodies have been demonstrated in some patients with T1D .…”

“…There are some reports that an immune response to proglucagon may occur in both NOD mice, as shown here, and in T1D patients . Indeed, glucagon‐specific antibodies have been demonstrated in some patients with T1D . Although attributed to ‘immunization’ by glucagon contaminants present in exogenously administered insulin, a spontaneous autoimmune response should also be considered in light of our findings in the NOD mouse.…”

“…Indeed, glucagon‐specific antibodies have been demonstrated in some patients with T1D . Although attributed to ‘immunization’ by glucagon contaminants present in exogenously administered insulin, a spontaneous autoimmune response should also be considered in light of our findings in the NOD mouse. Furthermore, autoantibodies against islet cells other than β cells (presumed to be α cells) have been reported in children before the onset of T1D and without exogenous insulin treatment .…”

Circulating Glucagon Antibodies in Children Who Have Insulin-dependent Diabetes Mellitus: Clinical Significance and Characterization

“…5 Stahl et al studied 72 sera from juvenile diabetics and found evidence of glucagon binding in only one specimen. 6 Cresto et al detected antibodies to glucagon in three of 85 insulin-requiring diabetics. 7 This combined experience gives a frequency of only 1.6% of insulin-requiring diabetic patients with antibodies to glucagon.…”