Nicardipine may impair glucose metabolism in hypertensive diabetic patients.

The respective effects of 6 month's administration of beta-blockers (atenolol, metoprolol, carteolol and arotinolol), calcium-channel blockers (nicardipine, diltiazem) and angiotensin converting enzyme inhibitor (enalapril) on hemoglobin A1c (HbA1c) levels were evaluated in hypertensive patients with non-insulin-dependent diabetes mellitus (NIDDM), using a retrospective method. NIDDM patients with stable HbA1c and body weight were selected for this study. The following results were obtained. (1) The administration of nicardipine or beta-blockers significantly elevated HbA1c levels. (2) The administration of diltiazem or enalapril did not have any influence on HbA1c levels. These findings suggest that not only beta-blocker but nicardipine (dihydropyridine type calcium-channel blocker) may cause deterioration in glucose metabolism in NIDDM patients.

Islet amyloid polypeptide (IAPP/amylin) causes insulin resistance in perfused rat hindlimb muscle.

It has been reported that islet amyloid polypeptide (IAPP) has insulin antagonistic effects in vivo and in vitro. To determine whether IAPP affects glucose metabolism in skeletal muscle, we performed in situ rat hindlimb perfusion which is a near-physiological system. Forty min after the beginning of insulin infusion at 1000 microU/ml, the synthesized rat amide form of IAPP was infused at 1 nM or 10 nM for 50 min and glucose concentration in the effluent was measured to calculate glucose uptake (GU). The GU did not change during the 1 nM IAPP infusion, but significantly decreased during 10 nM IAPP infusion (554 +/- 24 to 445 +/- 29 nmol/g/min, P less than 0.01). Rat calcitonin gene-related peptide (CGRP), which has sequence homology with IAPP and has been reported to inhibit insulin action, was also administered. Similar to the effect of IAPP, the GU did not change during 1 nM CGRP infusion but significantly decreased during 10 nM CGRP infusion (507 +/- 7 to 323 +/- 15 nmol/g/min, P less than 0.01). In the experiments without insulin infusion, the GU was not changed even by 10 nM IAPP infusion. Therefore, IAPP directly reduced only the insulin-mediated GU in the skeletal muscle, and this effect of IAPP occurred at the same dose as that of CGRP. These data suggest that both IAPP and CGRP may cause insulin resistance in skeletal muscle not through a CGRP receptor but a yet unknown receptor, which has similar binding affinity for both IAPP and CGRP.

Islet amyloid polypeptide amide causes peripheral insulin resistance in vivo in dogs.

Islet amyloid polypeptide is a 37 amino acid hormone-like peptide which is the major protein component of islet amyloid deposits commonly found in patients with Type 2 (non-insulin-dependent) diabetes mellitus. Recent studies indicate that a physiologically active form of this peptide appears to be carboxyamidated and secreted from the insulin-producing beta cell. In order to clarify the possible in vivo actions of islet amyloid polypeptide, we have studied the effects of synthesized islet amyloid polypeptide-amide on peripheral glucose utilization by performing hyperinsulinaemic euglycaemic glucose clamp studies on dogs. Exogenously administered islet amyloid polypeptide-amide (an infusion from 1.0 to 100 micrograms.kg-1.h-1, over 2 h) inhibited the insulin-stimulated glucose disposal rate in a dose dependent manner. Twenty-five micrograms.kg-1.h-1 of islet amyloid polypeptide-amide infused via a peripheral vein significantly lowered the glucose disposal rate by 20% (from 17.4 +/- 1.7 to 14.4 +/- 1.7 mg.kg-1.min-1, n = 5, p less than 0.01). These findings suggest that islet amyloid polypeptide-amide causes peripheral insulin resistance in vivo.

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.

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.

Comparative studies on vascular disorders in diabetics between urban and rural districts.

The incidence of vascular disorders was investigated in two groups of diabetics. One group (group-U) comprised 408 diabetics who were inhabitants of an urban district. The other group (group-R) consisted of 148 diabetics who were inhabitants of a rural district. The annual incidence rates of myocardial infarction and cerebrovascular disease in group-R were about twice as high as the respective rates in group-U. The prevalence rates of hypertension and ECG-abnormalities in group-R were also significantly higher than those in group-U (p less than 0.01). However, there was no appreciable difference between the two groups with respect to the incidence of proteinuria or proliferative retinopathy. Any significant difference between the two groups in age, obesity index, Hb-A1, T. Chol., TG. or HDL-C levels was not recognized. The duration of diabetes was relatively short in group-R. These findings suggest that the high incidence of myocardial infarction and cerebrovascular disease in group-R is not influenced by the difference in Hb-A1 or serum lipid levels, and that these vascular disorders are probably associated with hypertension and ECG-abnormalities.

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.

[Researches on the internal parasites in Ephemeroptera around Cracovie (author's transl)]. / Recherche sur les parasites internes des ephéméroptères de la région de Cracovie

For the first time, 7 kinds of internal parasites/Spiriopsis adipophila, Telomyxa glugeiformis, cysts of Crepidostomum farionis, Cystidicoloides and undetermined species of Microsporidia, Nematomorpha and Gordiacea are encountered in polish Ephemeroptera.