Diabetologia

Marble, A.

doi: 10.1007/BF00422085pmid: 782990

Joost, H.; Beckmann, J.; Holze, S.; Lenzen, S.; Poser, W.; Hasselblatt, A.

doi: 10.1007/BF00422086pmid: 782991

125 12 12 3 3 H. G. Joost J. Beckmann S. Holze S. Lenzen W. Poser A. Hasselblatt Institut für Pharmakologie und Toxikologie der Universität Göttingen Geiststr. 9 Göttingen Federal Republic of Germany Summary The tricyclic compound cyproheptadine (Periactinol®, Nuran®) inhibited glucose-induced insulin release from the perfused rat pancreas. Tolbutamide-stimulated insulin release was significantly reduced in the presence and completely suppressed in the absence of a substimulatory glucose concentration (5 mM). Arginine produced a slow rise of insulin release, which was completely abolished by cyproheptadine. Furthermore the biphasic glucagon release due to the stimulus was inhibited. Oxidation of 14 C-glucose in isolated islets was unaltered in the presence of cyproheptadine, and pyruvate added to the perfusion medium failed to reverse the inhibitory effect on glucose induced insulin release, indicating that impaired glucose metabolism is not responsible for the inhibition. In addition, the inhibition remained unchanged when phentolamine was present, suggesting that the effect is not mediated by inhibitory adrenergic alpha receptors. Theophylline, in contrast, partly overcame the inhibition. When the calcium concentration of the medium was enhanced, the inhibitory effect of cyproheptadine was still visible, although the relative inhibition had become smaller. The results suggest that cyproheptadine blocks insulin release by affecting a fundamental step of the stimulus-secretion coupling common to peptide hormones. A participation of a calcium-antagonizing effect in the inhibition is discussed.

Golden, P.; Baird, L.; Malaisse, W.; Malaisse-Lagae, F.; Walker, M.

doi: 10.1007/BF00422087pmid: 133846

125 12 12 3 3 Dr. P. Golden L. Baird W. J. Malaisse F. Malaisse-Lagae M. M. Walker Dept. of Pathology Washington Univ. School of Medicine St. Louis Missouri USA Dept. of Medicine Univ. of California at San Francisco The Moffitt Hospital 3rd and Parnassus San Francisco California USA Summary The present experiments were designed to compare the effects of streptozotocin and l-methyl-l-nitrosourea upon glucose-induced insulin secretion by isolated islets of Langerhans. Both drugs depressed the insulin response at one and two hours incubation but higher molar concentrations of the nitrosourea were required to produce the same level of inhibition as streptozotocin, a difference perhaps related to the latter's glucose moiety.

Larsson, L.; Sundler, F.; Håkanson, R.

doi: 10.1007/BF00422088pmid: 782992

125 12 12 3 3 Dr. L. -I. Larsson F. Sundler R. Håkanson Departments of Histology and Pharmacology University of Lund Lund Sweden Institute of Medical Biochemistry University of Aarhus DK-8000 Aarhus C Denmark Summary A peptide, referred to as pancreatic polypeptide (PP), has recently been isolated from the pancreas of chicken and of several mammals. PP is thought to be a pancreatic hormone. By the use of specific antisera we have demonstrated PP immunoreactivity in the pancreas of a number of mammals. The immunoreactivity was localized to a population of endocrine cells, distinct from the A, B and D cells. In most species the PP cells occurred in islets as well as in exocrine parenchyma; they often predominated in the pancreatic portion adjacent to the duodenum. In opossum and dog, PP cells were found also in the gastric mucosa. In opossum, the PP cells displayed formaldehyde-induced fluorescence typical of dopamine, whereas no formaldehyde-induced fluorescence was detected in the PP cells of mouse, rat and guinea-pig. Also in these latter species, however, PP cells appear to possess amine-handling properties, a feature common to many peptide hormone-producing cells. The ultrastructure of the PP cells was defined by combining immunohistochemistry of semi-thin plastic sections with electron microscopy of adjacent ultrathin sections. PP cells show the ultrastructural features of peptide hormone-secreting cells. The PP cells of cat and dog contain fairly large, rather electron-lucent granules, and are probably identical with the previously described F cells. The PP cells of rat, guinea-pig, chinchilla and man contain small, fairly electron-dense granules. In these latter species no F cells are found. By immunoperoxidase staining of ultrathin sections, the PP immunoreactivity was found to be localized to the cytoplasmic granules. These observations provide support for the view that PP is a true pancreatic hormone.

Klöppel, G.; Schäfer, H.

doi: 10.1007/BF00422089pmid: 782993

125 12 12 3 3 Dr. med. G. Klöppel H. -J. Schäfer Institute of Pathology University of Hamburg Federal Republic of Germany Pathologisches Institut der Univ. Martinistraße 52 2000 Hamburg 20 Federal Republic of Germany Summary The study examines the effects of sulfonylurea compounds on the histo- and ultracytochemical calcium distribution within the B-cells of mice using the glyoxal-bis-(2-hydroxyanil) (GBHA) and the pyroantimonate method combined with X-ray microanalysis. Treatment with tolbutamide (200 mg/kg), glibenclamide (2 mg/kg) and glisoxepide (2 mg/kg), causing moderate hypoglycemia and B-cell degranulation, was associated with an unchanged (30, 90 min) or slightly increased (180, 360 min, 4, 42 d) GBHA staining intensity of the islet cells compared with controls. Ultra-cytochemically sulfonylureas provoked, compared with controls, a redistribution of calcium-rich, electron dense pyroantimonate precipitates (EDPP). Precipitation predominantly occurred along the inner surface of the plasma membranes and within the granule halos. In contrast, the cytoplasmic matrix, the Golgi complexes and the rough endoplasmic reticulum contained only few fine precipitates. — The sulfonylureas investigated exerted identical effects on the histo- and ultracytochemical calcium distribution in B-cells. — The results indicate that sulfonylurea-induced insulin secretion is associated with an accumulation and redistribution of calcium within the B-cells. This supports the hypothesis that an altered calcium handling by the B-cell mainly accounts for the insulinotropic effect of sulfonylureas.

Timperley, W.; Ward, J.; Preston, F.; Duckworth, T.; O'Malley, B.

doi: 10.1007/BF00422090pmid: 955335

125 12 12 3 3 W. R. Timperley J. D. Ward F. E. Preston T. Duckworth B. C. O'Malley Departments of Neuropathology, Medicine, Haematology and Orthopaedics The Royal Infirmary Sheffield England Summary Sural nerve biopsy was performed in twenty-four diabetic patients, with clinical and electrophysiological evidence of diabetic neuropathy. Material from an autopsy case was also examined. Vessels plugged with fibrin were seen within nerve in nine cases. In three cases fibrin was observed tracking into the vessel wall and in four, older thrombus was observed in vessels. Areas of necrosis in nerve bundles were seen in two of the latter. In two patients there had been a preceding episode of intravascular coagulation. Fibrin deposition within small vessels could well play a part in damaging the diabetic nerve and a disturbance of the balance between deposition and removal by fibrinolysis could explain phasic variation in the symptoms of neuropathy.

Jonsson, A.; Wales, J.

doi: 10.1007/BF00422091pmid: 60265

125 12 12 3 3 A. Jonsson J. K. Wales University Department of Medicine, Martin Wing The General Infirmary at Leeds Leeds UK Summary Five glycoproteins have been measured in the blood of 145 diabetic patients with and without clinical evidence of complications. Patients with diabetic complications have higher glycoprotein levels particularly when expressed as a ratio to serum albumin levels. In 32 pairs of patients matched for age, sex, body weight, duration and treatment of diabetes, significantly higher haptoglobin, fibrinogen and caeruloplasmin levels were associated with the presence of diabetic complications, but blood glucose levels were not significantly different, β-lipoprotein levels were positively correlated with age and α 2 -macroglobulin levels with the duration of clinical disease, but the type of antidiabetic therapy administered did not significantly alter glycoprotein levels. It is suggested that rising levels of certain glycoproteins in the blood of diabetic patients may indicate the development of diabetic vascular complications, but a prospective study is required before it can be decided whether this change predates the clinical appearance of the complications.

Buck, A.; Reed, P.; Siddiq, Y.; Chisholm, G.; Russell Fraser, T.

doi: 10.1007/BF00422092pmid: 955336

125 12 12 3 3 A. C. Buck P. I. Reed Y. K. Siddiq G. D. Chisholm T. Russell Fraser Departments of Surgery and Medicine, Royal Postgraduate Medical School Hammersmith Hospital London England Summary Established urodynamic and electrophysiological techniques have been applied to assess the frequency and extent of autonomic and peripheral neuropathy in 60 subjects with diabetes mellitus; 38 were diabetics with suggestive symptoms and the others were representative newly diagnosed (11) or treated (11) diabetics. Objective evidence of neuropathic bladder dysfunction was detected in 43 of them (71.7%). The commonest abnormality was a hypotonic, insensitive large capacity bladder, which condition was usually asymptomatic. Less frequently (15%) this was complicated by bladder decompensation and sphincter involvement, resulting in excessive residual urine and infection; some of these had bladder paralysis with chronic painless retention of urine (7%). Electrophysiological studies found a sensory defect in the lower limbs in all tested patients (100%), and in 41 patients (69%) an associated motor conduction abnormality, which was more frequent and marked in the lower than the upper limb. These functional abnormalities appeared to be related to the severity of diabetes, but less to its duration. Indeed of 11 newly diagnosed diabetics tested 7 had a peripheral neuropathy and 4 urodynamic abnormalities. The high incidence of bladder dysfunction and peripheral neuropathy in this series indicates the frequency of subclinical diabetic neuropathy and a factor needing more emphasis in diabetic uropathy.

Ludwig, H.; Eibl, M.; Schernthaner, G.; Erd, W.; Mayr, W.

doi: 10.1007/BF00422093pmid: 955337

125 12 12 3 3 Dr. H. Ludwig M. Eibl G. Schernthaner W. Erd W. R. Mayr II. Medical Clinic, Institute of Immunology and Institute of Blood Group Serology University of Vienna Vienna Austria II. Med. Universitätsklinik Garnisonsgase 13 A-1097 Wien 9 Austria Summary Humoral immunity to bacterial antigens was tested in 49 tissue typed patients with juvenile onset diabetes mellitus (JOD) and in 50 healthy controls. The number of patients with agglutinins to E. coli and staphyloccoci was significantly lower compared to controls ( p <0.001, p <0.01 respectively). Missing antibody formation to pertussis and diphtheria toxoid could also be detected in a higher percentage of JOD patients than of controls ( p < 0.05; p ≃ 0.05, respectively). By contrast heteroagglutinins to sheep and rabbit erythrocytes were found in similiar proportion in both groups and the values of immunoglobulin serum concentrations showed no difference between patients and controls. In addition no correlation between antibody formation and genes of the HLA complex was found. It is suggested that the severely reduced agglutinin formation to bacterial antigens might be partly responsible for susceptibility to bacterial infections in juvenile diabetics.

Mennear, J.; Schonwalder, C.; Yau, E.

doi: 10.1007/BF00422094pmid: 782994

125 12 12 3 3 J. H. Mennear C. Schonwalder E. T. Yau Department of Pharmacology and Toxicology School of Pharmacy and Pharmacal Sciences Purdue University West Lafayette Indiana USA Summary The effects of barbituric acid and phenobarbital upon carbohydrate metabolism in mice were compared. An intraperitoneal dose of 100 mg/kg of barbituric acid increased blood glucose concentrations during an intravenous glucose tolerance test, but did not alter the rate of glucose disappearance from the blood. Barbituric acid also antagonized the hypoglycemic effect of intravenously administered tolbutamide. The same dose of phenobarbital had no effect. An in vitro concentration of 100 μg/ml of barbituric acid decreased the responsiveness of isolated mouse pancreatic islets to glucose stimulation (3.0 mg/ml D-glucose). Again phenobarbital, 100 μg/ml, was without effect. The structural similarities between barbituric acid, tolbutamide and alloxan suggest that the effects observed in these experiments might reflect a competition for binding to reactive sites on or within the pancreatic B-cell.