Diabetologia

Lernmark, Å.; Baekkeskov, S.

doi: 10.1007/BF00257781pmid: 7028555

Viberti, G.; Strakosch, C.; Keen, H.; Mackintosh, D.; Dalton, N.; Home, P.

doi: 10.1007/BF00257782pmid: 7028556

125 21 21 5 5 G. C. Viberti C. R. Strakosch H. Keen D. Mackintosh N. Dalton P. D. Home Unit for Metabolic Medicine Guy's Hospital Medical School London Department of Paediatrics Guy's Hospital Medical School London Department of Clinical Biochemistry The Royal Victoria Infirmary Newcastle-upon-Tyne UK Summary The circulatory, renal, and hormonal responses to physiological elevation of plasma insulin induced with oral glucose have been studied in seven healthy subjects. Glomerular filtration rate, urinary excretion rates of albumin and β 2 -microglobulin, haematocrit, pulse rate, blood pressure and plasma catecholamine concentrations have been measured. Physiological hyperinsulinaemia following glucose ingestion was associated with an increase in nor-adrenaline levels and brief tachycardia. No effect was noted on haematocrit, creatinine clearance, urinary albumin excretion, plasma adrenaline concentrations and arterial blood pressure. Urinary β 2 -microglobulin excretion rates fell shortly after the elevation of plasma insulin, probably indicating enhanced tubular reabsorption. Thus, glucose-induced physiological hyperinsulinaemia does not reduce glomerular filtration rate nor does it increase transglomerular passage of albumin, effects seen after the intravenous bolus injection of 6–8 U of insulin in diabetics.

Andrews, W.; Henry, R.; Alberti, K.; Buchanan, K.

doi: 10.1007/BF00257783pmid: 7028557

125 21 21 5 5 Dr. W. J. Andrews R. W. Henry K. G. M. M. Alberti K. D. Buchanan Department of Medicine The Queen's University Belfast Northern Ireland Department of Clinical Biochemistry University of Newcastle-Upon-Tyne UK Human Diabetes Study Center c/o NIH-NIADDK 4212 North 16th Street 85016 Phoenix AZ USA Summary A comparison of the metabolic and gastroentero-pancreatic hormonal responses of ten obese and eight lean subjects to 12 h and 36 h fasts has been made. Each subject was given a 50 g oral glucose tolerance test at the end of both 12 h and 36 h starvation. After the 12 h fast blood glucose and 3-hydroxybutyrate were similar in each group but blood glycerol was 30% higher in the obese subjects. Plasma insulin and vaso-active intestinal polypeptide were also higher in the obese subjects after 12 h starvation. After 36 h starvation in the lean subjects blood glucose was unchanged but on refeeding with 50 g oral glucose, glucose tolerance was impaired. In the same group blood glycerol and 3-hydroxybutyrate rose after 36 h starvation. Plasma glucagon, secretin and vaso-active intestinal polypeptide rose after 36 h starvation in the lean subjects but plasma insulin was unchanged. Refeeding with oral glucose suppressed the increased plasma glucagon, secretin and vaso-active intestinal polypeptide. After the 36 h fast in the obese subjects, blood glucose was unchanged, blood glycerol fell, but blood 3-hydroxybutyrate rose although to a reduced level in comparison with the lean subjects. In the obese group there was no change in plasma glucagon, secretin or vaso-active intestinal polypeptide after 36 h starvation, although plasma insulin fell. The results show different metabolic and gastro-entero-pancreatic hormonal responses to fasting in lean and obese human subjects and suggest an important metabolic role of glucagon, secretin and vaso-active intestinal polypeptide during starvation.

Gérard, J.; Luyckx, A.; Lefebvre, P.

doi: 10.1007/BF00257784pmid: 7028558

125 21 21 5 5 J. Gérard A. S. Luyckx P. J. Lefebvre Division of Diabetes Institute of Medicine, University of Liège Belgium Summary Acarbose, an α -glucosidase inhibitor, delays starch digestion and inhibits intestinal sucrase and maltase activity. Twenty-eight insulin dependent diabetics were given Acarbose (3×100 mg daily) over a two month period, preceded and followed by a two month placebo period. Acarbose reduced post-break-fast and post-dinner blood glucose values by 25% (p <0.001) and 24% (p<0.05) respectively. It also significantly reduced mean daily blood glucose by 18% ( p < 0.05) and mean amplitude of glycaemic excursions from 8.0±0.6 to 5.5±0.4 mmol/l ( p <0.0005). Weight did not change significantly. Daily caloric and carbohydrate intake remained constant throughout the study while insulin requirements decreased slightly but significantly. Out of the 28 patients, 18 had absent while ten had slight residual B cell function as assessed by plasma C-peptide measurements. Treatment with Acarbose did not significantly affect residual B cell function. The beneficial effect of Acarbose on blood glucose control was seen in patients both with and without residual B cell secretion. The major side-effect was flatulence which was never severe enough to interrupt treatment, but led to a 50% reduction of the dose in one patient. It is concluded that Acarbose represents a useful additional means of improving metabolic control in insulin dependent diabetics.

Assan, R.; Efendic, S.; Luft, R.; Cerasi, E.

doi: 10.1007/BF00257785pmid: 7028559

125 21 21 5 5 R. Assan S. Efendic R. Luft E. Cerasi Diabetes Department Bichat Hospital Paris France Department of Endocrinology Karolinska Hospital Stockholm Sweden Department of Endocrinology and Metabolism Hadassah University Hospital Jerusalem Israel Summary Pancreatic glucagon responses to different amounts of intravenous arginine and glucose were studied in 10 insulin-dependent diabetics, 14 healthy controls (high insulin responders) and 15 subjects with decreased insulin response to glucose but normal intravenous glucose tolerance (low insulin responders). The dose-kinetics of the glucagon response was studied by using four different arginine doses. The suppressive effect of glucose was evaluated by infusing three glucose doses during a submaximal stimulation with arginine. The diabetics were tested first when under fair metabolic control and then following intensive treatment with insulin to produce near-normalisation of blood glucose. Finally, five subjects underwent insulin-induced hypoglycaemia. The changes in plasma glucagon and blood α -amino-nitrogen in response to the four arginine doses were significantly correlated in all groups but the slope of the dose response curve was steeper in the poorly controlled-diabetics than in the non-diabetics. These diabetics displayed higher fasting plasma glucagon values than healthy controls (high insulin responders) (224±4 versus 151±22 pg/ml, p <0.01), higher plasma glucagon responses to arginine and an absence of inhibition by glucose of the arginine-stimulated glucagon release. In strictly controlled diabetic patients, fasting plasma glucagon levels (176±16 pg/ml) were not significantly different from healthy controls, the glucagon response to arginine returned to the normal range, A cell suppressibility by glucose was restored and A cell stimulation by hypoglycaemia reappeared. In the low insulin responders, fasting plasma glucagon was not different from that of high responders (107±12 pg/ml), the slope of the dose response curve to arginine was similar in both groups and the A cells were inhibited by glucose to a similar extent. These results support the concept that islet A cell dysfunction in diabetes is not a primary phenomenon.

Williams, R.; Knowler, W.; Butler, W.; Pettitt, D.; Lisse, J.; Bennett, P.; Mann, D.; Johnson, A.; Terasaki, P.

doi: 10.1007/BF00257786pmid: 7297796

125 21 21 5 5 R. C. Williams W. C. Knowler W. J. Butler D. J. Pettitt J. R. Lisse P. H. Bennett D. L. Mann A. H. Johnson P. I. Terasaki Department of Anthropology Arizona State University Tempe Arizona Southwestern Field Studies Section National Institute of Arthritis, Mebabolism and Digestive Diseases Phoenix Arizona Immunology Branch National Cancer Institute Bethesda Maryland Division of Immunology Duke University Durham North Carolina Department of Surgery University of California Los Angeles Los Angeles California USA Summary In Pima Indians with Type 2 (insulin independent) diabetes mellitus, HLA-A2 allele frequencies were inversely associated with age, (0.72, 0.59, and 0.52 in those less than 35, 35 to 54, and 55 years old and over, respectively). This suggests that there may be a gene closely linked with the HLA-A locus which plays a role in the expression of diabetes in the Pimas by contributing to an earlier age of onset. HLA-A2 was found in 65% of 69 non-diabetic and 81% of 191 diabetic subjects (relative risk = 2.2).

Taylor, C.; Varandani, P.

doi: 10.1007/BF00257787pmid: 7028560

125 21 21 5 5 C. A. Taylor P. T. Varandani Fels Research Institute and Department of Biological Chemistry School of Medicine and College of Science and Engineering, Wright State University Yellow Springs Ohio USA Summary Glutathione-insulin transhydrogenase catalyzes the inactivation of insulin by splitting the hormone into A and B chains. We have localized this enzyme immunocytochemically by light microscopy in the pancreas, kidney and liver of both lean and obese (ob/ob) mice and similarly in normal and streptozotocin-diabetic rats. Localization was achieved by an antibody to glutathione-insulin transhydrogenase using a peroxidase-antiperoxidase technique. In comparison with tissues from control animals, positive immunostaining for glutathione-insulin transhydrogenase was increased in the obese mouse but reduced in the diabetic rat. Different tissues showed considerable variation in the amount of glutathioneinsulin transhydrogenase which could be detected. In the pancreatic islets there was little or no evidence for the presence of the enzyme in peripheral cells. In the kidney, immunocytochemical staining was found only in the proximal tubules. In the liver there was a generalised distribution of the enzyme, but the greatest concentration was in the periportal region. These observations parallel the biochemical data relating to glutathione-insulin transhydrogenase, indicating that different amounts of insulin degrading activity exist in different regions of tissues.

Scott, A.; Atwater, I.; Rojas, E.

doi: 10.1007/BF00257788pmid: 7028561

125 21 21 5 5 A. M. Scott I. Atwater E. Rojas Department of Biophysics School of Biological Sciences, University of East Anglia Norwich Norfolk UK Summary A method has been developed for the simultaneous measurement of insulin release and electrical activity in single micro-dissected mouse islets of Langerhans. The effects of D-glucose have been studied in individual islets. Each islet was exposed to 0, 5.6, 11.1, 16.7, 22.2, 27.8 and 33.3 mmol/l glucose in a stepwise fashion. The minimum glucose concentration required to elicit spike activity is lower than that required to stimulate insulin release above basal levels and the maximum spike frequency occurs at a lower glucose concentration than does maximum insulin release. Following a reduction in glucose from 27.8 (or 33.3) to 5.6 mmol/l, membrane potentials returned to resting values within 2 min whereas insulin returned to basal values after 20 min. Increasing glucose from 5.6 to 27.8 mmol/l induced spike activity within 10 s; the insulin response was detected within 40 s. Thus, it is possible to use the single mouse islet for simultaneous measurements of insulin release and electrical activity.

Rossi, G.; Bestetti, G.

doi: 10.1007/BF00257789pmid: 7028562

125 21 21 5 5 G. L. Rossi M. D. G. Bestetti Institute of Animal Pathology University of Berne Switzerland Institut für Tierpathologie Universität Bern Postfach 2735 CH-3001 Bern Switzerland Summary The hypothalami, pituitaries and testes from streptozotocin-treated and control male Wistar rats were examined by light and electron microscopy 12 months after induction of diabetes. Light and electron microscopic immunohistochemical techniques were employed for the localization of luteinizing hormone-releasing hormone and luteinizing hormone in the hypothalami and the pituitaries. In the hypothalami of diabetic animals swollen neuronal processes containing anti-luteinizing hormone-releasing-hormone positive material were frequent. In the pituitaries of the same animals a large number of small luteinizing hormone-gonadotrophs was found. These cells contained numerous secretory granules and were deficient in endoplasmic reticulum. The average testicular weight of the diabetic rats was significantly reduced but with marked individual variations. Histologically, the testes with the highest weights appeared normal, those with the lowest weights atrophic with few degenerating Leydig cells. These hypothalamic-hypophyseal changes are probably responsible for the testicular lesions found in experimental diabetes mellitus and may have relevance to the problem of infertility in human diabetes.

Yu, K.; Gould, M.

doi: 10.1007/BF00257790pmid: 6795077

125 21 21 5 5 K. T. Yu M. K. Gould Department of Biochemistry Monash University Clayton Victoria Australia Summary The uptake of D-xylose by isolated rat soleus muscle (measured at 37 °C) was stimulated by prolonged cooling at 0 °C. The effect of cooling reached a maximum value after 3 h and was reversed on rewarming; reversal was temperature-dependent. Cooling stimulated xylose uptake sub-maximally compared with the effect of insulin (100 U/l). Xylose uptake in cooled muscle was further stimulated by insulin, but not by anoxia. The effect of cooling and its reversal were still demonstrable in the presence of ouabain (1 mmol/l), or when unidirectional efflux of calcium and magnesium from the muscle was induced by EDTA (5 mmol/l). The ionophore, A23187 (2.5 mg/l), depressed the effect of cooling in the presence of EDTA but not in the presence of EGTA. It is concluded that cooling disrupts an intracellular magnesium-pump and that muscle sugar transport is consequentially stimulated through an increase in cytoplasmic magnesium.