Diabetologia

Goulder, T.; Alberti, K.

doi: 10.1007/BF02573820pmid: 710750

Beck-Nielsen, H.; Pedersen, O.; Schwartz Sørensen, N.

doi: 10.1007/BF02573821pmid: 710751

125 15 15 4 4 H. Beck-Nielsen O. Pedersen N. Schwartz Sørensen Medical Department III and Department of Clinical Chemistry County Hospital Tage Hansensgade Århus Denmark Nutrition Laboratory, Institute of Hygiene University of Aarhus Denmark Summary To ascertain whether the effects of diet on glucose tolerance and insulin sensitivity are mediated through changes of insulin receptors we have studied insulin binding to monocytes in 24 young volunteers (4 groups of 6) during 2 week periods of different dietary regimens. In group 1 and 2 the subjects had their usual diet plus 1000 kcal per day from sucrose or fat, respectively. Group 3 had an isocaloric diet with a low-sucrose content, while group 4 ate low-fat high carbohydrate diets. Before change of diet the total group of volunteers showed an inverse correlation between insulin binding and average daily sucrose intake (R = − 0.52, p<0.01). An excessive sucrose consumption (group 1) was associated with a reduction both of insulin binding (p<0.05) and insulin sensitivity (p<0.05). The changes of the two variables were parallel (R = 0.95, p<0.05). An abundant fat intake (group 2) was also accompanied by a decrease of insulin binding (p<0.05). However, insulin sensitivity was unaltered (p>0.1). A rise of insulin binding (p<0.05) followed the isocaloric, low-sucrose diet (group 3) whereas the insulin sensitivity was unchanged (p>0.1). After the isocaloric, low-fat diet (group 4) no significant change of insulin binding occurred (p>0.1) whereas the insulin sensitivity increased (p<0.05). We conclude that diet and especially the dietary sucrose content affect insulin binding to human monocytes. Evidence is presented that changes of insulin sensitivity following hyperalimentation of sucrose may be induced through alterations of insulin receptors.

Scandellari, C.; Zaccaria, M.; Palo, C.; Sicolo, N.; Erle, G.; Federspil, G.

doi: 10.1007/BF02573822pmid: 213332

125 15 15 4 4 C. Scandellari M. Zaccaria C. De Palo N. Sicolo G. Erle G. Federspil Institute of Medical Semeiology University of Padua Italy Department of Metabolic Diseases City Hospital of Vicenza Italy Summary Five hypoglycaemic hyperinsulinaemic patients (three with proven benign insulinoma, one with proven metastasizing insulinoma, one with probable insulinoma not found at surgery) were treated with propranolol for a variable time ranging from two weeks to one year. Three patients showed favourable clinical results and a significant increase of the mean basal blood glucose level was found while two patients showed no improvement of the frequency of neuroglycopenic episodes and no significant increase of their mean basal blood glucose level. No patient showed a significant decrease in mean basal IRI concentration. A decrease of insulinaemic responses was observed during oral and intravenous glucose tolerance tests, a prolonged fast, and tolbutamide and glucagon tests performed in some patients. The results suggest that propranolol may induce in certain patients an improvement of basal clinical status through not undestood effects (probably hepatic), which leave the peripheral concentrations of insulin unchanged, whereas inhibition of insulin secretion may represent the main way by which the improvement of metabolic situation during physiological or pharmacological stimulation may have been achieved.

Albisser, A.; Ellman, J.; Hanna, A.; Goriya, Y.; Minuk, H.

doi: 10.1007/BF02573823pmid: 710752

125 15 15 4 4 A. M. Albisser J. Ellman A. Hanna Y. Goriya H. Minuk The Hospital for Sick Children Toronto Canada Summary A practical method for continuous blood glucose analysis in vivo is described. Using an interference-free enzyme reagent in a modified Auto-Analyzer whole blood glucose concentration can be monitored continuously and interpreted in terms of the actual plasma glucose concentration. The method uses a novel technique for preheating the sample diluent without introducing additional time delays, consumes whole blood at a rate of 0.05 ml/min, and demonstrates a transport delay of 148 s. Other improvements include an average baseline drift of −0.11 mg/dl/h and a mean change in sensitivity of −0.4% after 8.5 h. In vitro glucose recovery studies comparing whole blood to the corresponding plasma samples show the method is precise (101.3±0.7%), linearly proportional (slope of 1.007±0.012) and highly correlated (>0.998) over the range of 0 to 500mg/dl, with reference to a Beckman glucose analyzer. In vivo applications are presented to show that this method is suitable for use in systems such as the ‘artificial endocrine pancreas’.

Yagihashi, S.; Goto, Y.; Kakizaki, M.; Kaseda, N.

doi: 10.1007/BF02573824pmid: 710753

125 15 15 4 4 S. Yagihashi Y. Goto M. Kakizaki N. Kaseda First Department of Pathology and Third Department of Internal Medicine Hirosaki University School of Medicine Hirosaki Japan Third Department of Internal Medicine Tohoku University School of Medicine Sendai Japan Summary The glomerular basement membrane of spontaneously diabetic rats was investigated by quantitative analysis using electron microscopy, with special reference to the effect of ageing. Constant agerelated increase in the width of basement membrane was ascertained both in diabetic and control rats, and the mean values of basement membrane thickness were always higher in the spontaneously diabetic rats than in normal control rats. Significant thickening of glomerular basement membrane was found in the diabetic rats at 12 weeks of age, while younger diabetic rats had no definite increase. The difference in basement membrane thickness between diabetic and normal control rats became larger with increasing age.

Laurent, F.; Mialhe, P.

doi: 10.1007/BF02573825pmid: 710754

125 15 15 4 4 F. Laurent P. Mialhe Laboratoire de Physiologie Générale Strasbourg France Summary The relationship between two metabolites, free fatty acids (FFA) and amino acids (AA), and the two main pancreatic hormones, insulin and glucagon, was studied by infusing small amounts of these metabolites into normal and diabetic Peking ducks, i. e. two days after subtotal pancreatectomy. Infusion of oleic acid (0.365 g/kg/30 min as an emulsion in plasma) indicated a suppressive effect of free fatty acids on glucagon secretion, but was without effect on insulin secretion, in normal as well as in diabetic ducks, indicating that insulin might not be directly involved in the FFA-glucagon feedback in the duck. Infusions of arginine for one hour (1 g/kg/h) into normal ducks, hyperglycaemic normal birds (as a result of glucose infusion: 1 g/kg/h) and diabetic ducks, suggested the persistence of an amino acid effect on glucagon secretion, and a slight reduction of the effect on insulin secretion in diabetes. This suggests that insulin may not be involved in amino acidinduced glucagon secretion in the duck.

Stout, R.

doi: 10.1007/BF02573826pmid: 213333

125 15 15 4 4 R. W. Stout Department of Geriatric Medicine The Queen's University of Belfast Belfast Northern Ireland Summary The smooth muscle cell plays an important role in the process of atherogenesis. In these experiments the effect of glucagon and dibutyryl cyclic AMP on sterol synthesis in cultured rat arterial smooth muscle cells was studied. Glucagon in concentrations of 1×10 −9 mol/l inhibited the incorporation of sodium (2− 14 C)acetate into non-saponifiable lipids and digitonin precipitable sterols but lower concentrations of glucagon had no effect. In cells which were exposed to serum, dibutyryl cyclic AMP also resulted in a decrease in the incorporation of labelled acetate into sterols but when the cells were grown in serum free medium, dibutyryl cyclic AMP had no inhibitory effect on sterol synthesis. These results provide further evidence that sterol metabolism in arterial smooth cells may be influenced by hormones but suggest that glucagon is relatively less important than insulin in this respect.

Appel, M.; Rossini, A.; Williams, R.; Like, A.

doi: 10.1007/BF02573827pmid: 213334

125 15 15 4 4 M. C. Appel A. A. Rossini R. M. Williams A. A. Like Department of Pathology University of Massachusetts Medical School Worcester Massachusetts Department of Medicine, Harvard Medical School Boston Elliott P. Joslin Research Laboratory and Division of Tumor Immunology, Sidney Farber Cancer Institute Massachusetts USA Summary Multiple injections of streptozotocin to Charles River (CD-1) Laboratory mice resulted in a syndrome characterised by diabetes mellitus, insulitis and the induction of endogenous type C viruses in pancreatic beta cells. Within one week after the completion of five intraperitoneal injections of streptozotocin, the CD-1 mice exhibited irreversible hyperglycaemia and insulinopaenia. Light microscopic studies of pancreata from mice sacrificed at this time demonstrated insulitis and beta cell necrosis. Electron microscopic studies revealed spherical and atypical cylindrical type C viruses and occasional clusters of intracisternal type A viruses exclusively within beta cells. To clarify the identification of the type C viruses and their role in the genesis of the insulitis, type C virus specific antigens were identified within islet cells by immune fluorescence at various intervals after streptozotocin administration. Immune fluorescence studies demonstrated the presence of type C virus antigens within islets from streptozotocin treated mice but not in buffer-injected controls. Time course studies suggested that type C virus induction may precede the appearance of insulitis by two days and that insulitis is consistently accompanied by the presence of virus positive islet cells.

Landgraf-Leurs, M.; Mayer, L.; Landgraf, R.

doi: 10.1007/BF03160999pmid: 710755

125 15 15 4 4 M. M. C. Landgraf-Leurs L. Mayer R. Landgraf Medizinische Klinik Innenstadt der Universität Ziemssenstrage 1 D-8000 München 2 Germany Summary Using the isolated, perfused rat pancreas the importance of sulphydryl groups for the secretory process of insulin was investigated. It was found that ethacrynic acid (EA, 0.075–0.6 mmol/1) caused a dose-dependent, monophasic insulin release. Addition of EA to a glucose-stimulated (20 mmol/1) pancreas led to a sudden increase in hormone release, followed by a dose-dependent inhibition of release, which was not reversible after removal of EA. The same phenomenon was seen in the presence of 20mmol/1 leucine. Dithiothreitol (DTF, 0.1 and 1 mmol/1) had no effect on basal insulin secretion. Added to a glucose-stimulated pancreas DTF (1 mmol/1) caused a reversible inhibition of insulin release. The persistent inhibitory action of EA on glucose-induced insulin release could be reversed by simultaneous perfusion of EA and DTT. Sequential exposure of a glucose-stimulated pancreas to EA and DTT led to a rapid release of insulin, due to DTT; however, the EA-induced inhibition of insulin secretion could not be prevented. Two kinds of thiol groups in the plasma membrane and in the beta cell might be responsible for the various kinetics of insulin release induced by EA and DTT.

Hermansen, K.

doi: 10.1007/BF03161000pmid: 710756

125 15 15 4 4 K. Hermansen Second University Clinic of Internal Medicine Kommunehospitalet DK-8000 Aarhus C Denmark Summary The effect of haloperidol, a dopaminergic antagonist, on insulin and glucagon secretion was investigated using the isolated, perfused canine pancreas. Haloperidol at 4 × 10 −7 to 10 −5 mol/l caused a dose-dependent inhibition of glucagon release both at low (25 mg/100 ml) and high glucose concentrations (150 mg/100 ml). At the low glucose concentration insulin release was already maximally suppressed. At the high glucose concentration haloperidol (4 × 10 −7 to 10 −5 mol/l) also caused a dose-dependent inhibition of insulin release. Haloperidol (10 −5 mol/l) inhibited dramatically pancreatic A and B cell responses to isoproterenol (2 ng/ml), acetylcholine (1 μmol/l) and arginine (5mmol/l). The inhibitory effect of haloperidol on both glucagon and insulin release could be eliminated by increasing perfusate calcium concentration from 1.3 to 8.8 mmol/l. These findings suggested that haloperidol blocks glucagon and insulin release in a somatostatin-like manner by affecting a fundamental step of the stimulus-secretion coupling, probably by interfering with calcium handling of the pancreatic A and B cells.