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T Sanke

Publications and source records attributed to T Sanke.

71 records · Page 4Linked to original sources
PubMed1988

Use of in vitro DNA amplification to screen family members for an insulin gene mutation.

The DNA polymerase chain reaction can be a powerful tool for amplifying selected segments of genomic DNA for investigation of point mutations that are inaccessible via classic restriction-fragment-length polymorphism analysis. We have applied this method to an analysis of the incidence of heterozygosity for the mutant insulin allele insulin Wakayama (A3 Val----Leu) in two unrelated Japanese families having the hyperinsulinemic mutant insulin syndrome. The results indicate that this method is simple, sensitive, and accurate and should be useful for screening larger (diabetic) populations to detect single-base substitutions in the insulin gene that lead to either altered (pro)insulin structure and/or insulin production.

Amino Acid Sequence↗
PubMed1987

Insulin Wakayama: familial mutant insulin syndrome in Japan.

We describe a family from Japan displaying the mutant insulin syndrome with hyperinsulinaemia and an increased insulin: C-peptide molar ratio. Serum insulin isolated from several family members showed reduced in vitro biological activity, and analysis by high performance liquid chromatography revealed a peak co-eluting with human insulin and a second species of increased hydrophobicity co-migrating with the previously reported Insulin Wakayama. The insulin genes from the propositus were cloned and sequenced, revealing one normal allele; the second allele, encoding a leucine for valine amino acid substitution at position 3 of the insulin A chain, was similar to that previously described for Insulin Wakayama. Synthesized [LeuA3] insulin showed 0.14% of receptor binding activity on rat adipocytes and a 10-fold prolonged half-life in a somatostatin-infused dog compared with human insulin. The finding of the same mutant gene in two unrelated Japanese families suggests that Insulin Wakayama may be discovered in additional Japanese families with hyperinsulinaemia and/or diabetes.

Adult↗
PubMed1986

Effect of calcium antagonists on reactive hypoglycemia associated with hyperinsulinemia.

The clinical usefulness of calcium antagonists was studied in four patients with reactive hypoglycemia including two with alimentary and two with idiopathic. All patients had hyperresponses of plasma insulin (IRI) and C-peptide (CPR) during an oral glucose tolerance test (OGTT). A calcium antagonist (diltiazem 90 mg/d, or nifedipine 30 mg/d, or nicardipine 60 mg/d) was administered orally for about two months. After two months of treatment, plasma IRI and CPR responses during the OGTT were clearly suppressed in all patients and symptomatic reactive hypoglycemia disappeared. One month after the discontinuation of the treatment in two patients, plasma IRI and CPR responses during the OGTT became higher again and symptomatic reactive hypoglycemia recurred. In addition, an intravenous glucose tolerance test was performed before and after two months of the treatment with calcium antagonists in the two patients with reactive hypoglycemia and seven patients with hypertension, who were free from glucose intolerance and were also treated with a calcium antagonist. In these patients, plasma IRI and CPR responses were also reduced after the treatment compared with those before the treatment. These results suggest that calcium antagonists are useful as therapeutic agents for the treatment of reactive hypoglycemia associated with hyperinsulinemia, and that one of the main mechanisms of action of calcium antagonists is a direct action on the pancreatic B-cell to inhibit glucose-induced insulin release.

Adult↗
PubMed1986

Properdin factor B frequencies in four Asian populations.

The distribution of Properdin factor B (Bf) phenotypes and their gene frequencies were investigated in four Asian populations (Chinese, Filipino, Thai and Japanese). The frequency of the BfS phenotype in Filipinos (0.717) was significantly lower than that in Chinese (0.900) and Thai (0.889) (p less than 0.01), but not different from the Japanese (0.840). One variant, BfF 0.65 S, was identified in a Japanese subject. Thus, in the Asian populations studied, Bfs frequencies were high and the frequency of variants other than F and S were low.

China↗
PubMed1986

Diabetes due to secretion of a structurally abnormal insulin (insulin Wakayama). Clinical and functional characteristics of [LeuA3] insulin.

We have identified a non-insulin-dependent diabetic patient with fasting hyperinsulinemia (90 microU/ml), an elevated insulin:C-peptide molar ratio (1.68; normal, 0.05-0.20), normal insulin counterregulatory hormone levels, and an adequate response to exogenously administered insulin. Insulin-binding antibodies were absent from serum, erythrocyte insulin receptor binding was normal, and greater than 90% of circulating immunoreactive insulin coeluted with 125I-labeled insulin on gel filtration. The patient's insulin diluted in parallel with a human standard in the insulin radioimmunoassay, confirming close molecular similarity. The patient's insulin was purified from serum and shown to possess both reduced binding and ability to stimulate glucose uptake and oxidation in vitro. Analysis of the patient's insulin by high-performance liquid chromatography (HPLC) revealed two products: 7.3% of insulin immunoreactivity coeluted with the human standard, while the remaining 92.7% eluted as a single peak with increased hydrophobicity. Family studies confirmed the presence of hyperinsulinemia in four of five relatives in three generations, with secretion of an abnormal insulin documented by HPLC in the three tested. Leukocyte DNA was harvested from the propositus and the insulin gene cloned. One allele was normal, but the other displayed a thymine for guanine substitution at nucleotide position 1298 from the putative cap site, resulting in a leucine for valine substitution at position 3 of the insulin A chain. Insulin Wakayama is therefore identified as [LeuA3] insulin.

Adipose Tissue↗
PubMed1983

Three mutant insulins in man.

We have previously identified a structurally abnormal insulin in the serum and pancreas of a middle-aged man with diabetes mellitus which arose from a leucine for phenylalanine substitution at position 24 or 25 of the insulin B chain; further analysis of the patient's leukocyte DNA showed that one of the patient's insulin alleles had undergone mutation resulting in loss of an MboII restriction site normally present in the human insulin gene. Two additional and unrelated patients with the same clinical syndrome have now been identified (ref. 4 and unpublished results). All of these patients showed hyperglycaemia typical of diabetes and with marked hyperinsulinaemia typical of insulin resistance, but all three show normal tolerance to exogenously administered insulin. As the opportunity of examining pancreatic tissue from patients suspected of secreting insulin variants is rare, we have developed a method combining HPLC and radioimmunoassay to identify insulin variants isolated from human sera. By this method we have shown that all three patients noted above secrete structurally variant and chemically distinct insulins. In correction of our original assignment, one is identified as [LeuB25]insulin.

Amino Acid Sequence↗
PubMed1983

Glucagon binding autoantibodies in a patient with hyperthyroidism treated with methimazole.

A 47-yr-old woman who had previously received methimazole (MMI) treatment for hyperthyroidism was found to have glucagon binding autoantibodies in plasma. She had never received glucagon. The binding substances were detected in plasma at the time of a glucagon RIA. [125I]Glucagon binding was inhibited only by porcine glucagon and porcine glicentin, and dissociated at acid pH. The substances proved to be glucagon binding antibodies (immunoglobulin G, L-chain K-type), as determined by ammonium sulfate and radioprecipitation. There were no clinical manifestations related the presence of these autoantibodies. In a survey of 91 patients with thyroid disease, 3 patients whose plasma bound [125I]glucagon were identified among 41 with hyperthyroidism who were receiving MMI treatment. Such binding was not found in plasma from untreated hyperthyroid patients, those receiving propylthiouracil or those with chronic thyroiditis. These findings suggest that the development of glucagon antibodies in hyperthyroidism may be associated with MMI treatment.

Autoantibodies↗
PubMed1983

Proposal of the diabetic diet load test (DLT) as a new diagnostic.

The diet loading test (DLT), which measures the change in the blood sugar (BS) level after a loading diabetic diet (5 units = 400 kcal, including 50 g of carbohydrate), has been devised as a new diagnostic for diabetes. Twenty-seven and 253 patients classified as borderline type (G-B) and diabetic type (G-DM), respectively, from the results of 50 g-OGTT (GTT) were subjected to DLT to evaluate its clinical usefulness. Diagnostic criteria of DLT were established from the BS levels (mean +/- 2S.D.) in 46 normals as follows: normal type (D-N), lower than 100 mg/100 ml at baseline and than 120 mg/100 ml both 1 and 2 hr after loading; diabetic type (D-DM), higher than 120 mg/100 ml at both 1 and 2 hr; borderline type (D-B), neither of these patterns. According to these criteria, 253 patients of G-DM were divided into 249 D-DM and 4 D-B; 27 G-B were subclassified into 3 groups: 7 D-N (all of them were above 70 years old), 13 D-B and 7 D-DM (all of them were in a remission stage of diabetes). Furthermore, the results of DLT were more closely correlated with HbA1 levels, the daily profile of BS and the degree of retinopathy than those of GTT. The reproducibility of DLT was also better than that of GTT. In conclusion, DLT is a new system which makes it possible to differentiate physiological glucose intolerance in the aged and in patients in a remission state of diabetes from borderline cases diagnosed with GTT. Furthermore, it was proved that a better correlation existed between the state of BS control and the results of DLT than those of GTT. The usefulness of DLT in a population survey was also proved.

Aged↗
PubMed1982

Size heterogeneity of immunoreactive glucagon during bile-duct obstruction in the rabbit.

The influence of bile-duct obstruction upon basal plasma glucagon levels and the relationship between glucagon-like substance in bile and postobstructive plasma glucagon were examined in the rabbit. Immunoreactive glucagon (IRG) was measured with antiserum 30 K (Unger). Bile-duct obstruction was followed by a prompt rise within 60 minutes in plasma IRG which was four times the basal value, but had little influence on plasma immunoreactive insulin and blood sugar. The biliary IRG and the elevated plasma IRG during bile-duct obstruction were filtered with a Bio-Gel P-10 column. Most of the postobstructive plasma IRG appeared in the void volume area (plasma large IRG), while almost all of the biliary IRG was recovered in the position equivalent to approximately 2000 daltons (biliary IRG 2000). Both IRGs of different molecular sizes revealed similar dilution curve in radioimmunoassay to that with porcine glucagon. After incubation of bile with preobstructive plasma, the IRG elution profile of the mixture contained an increased amount of large molecular size IRG similar to that of postobstructive plasma in regard to 30K specificity and elution position. The disappearance of IRG in the void volume area was observed when the bile-plasma mixture or the postobstructive plasma was filtered with acidic buffer. These results suggest that plasma large IRG contributing to hyperglucagonemia during bile-duct obstruction may be derived from biliary IRG 2000.

Animals↗