Diabetologia

Alford, F.; Bloom, S.; Nabarro, J.

doi: 10.1007/BF00996319pmid: 838198

125 13 13 1 1 Dr. F. P. Alford S. R. Bloom J. D. N. Nabarro Cobbold Laboratories Middlesex Hospital Medical School London England Endocrine Unit St. Vincent's Hospital 3067 Fitzroy Vic. Australia Summary Non-specific plasma effects may produce major errors in the estimation of true plasma pancreatic glucagon concentrations by radioimmunoassay. This has been circumvented by the production of glucagon-free plasma for each individual investigated, by means of glucagon antibody, coupled to sepharose beads. True fasting pancreatic glucagon levels (mean ± SEM) in 18 healthy subjects (24 ± 3 pg/ml) were significantly lower (p < 0.005) than in 10 non-ketotic non-obese diabetics (38 ± 3 pg/ml). It is suggested that, in the presence of decreased insulin-effect in the diabetic, this 55% glucagon elevation in diabetics may be of biological importance and contribute to the fasting hyperglycaemia.

Tuman, R.; Doisy, R.

doi: 10.1007/BF00996320pmid: 838204

125 13 13 1 1 R. W. Tuman R. J. Doisy Department of Biochemistry State University of New York, Upstate Medical Center Syracuse New York USA Summary The effect of spontaneous diabetes on plasma lipids during the natural course of the disease was studied in genetically diabetic mice (C57BL/KsJ-db/db). Hyperlipidaemia developed uniformly in all mice studied and was found to be a characteristic part of the diabetic syndrome, as compared to normal littermates. The hyperlipidaemia was characterized by a marked rise in plasma triglyceride levels with age and severity of the disease, increasing from 120 ±6 mg/dl at 5 weeks of age to 400 ± 91 mg/dl at 19 weeks of age. In addition, db/db mice were observed to be hypercholesterolaemic as compared to age-matched normal littermates. The plasma cholesterol levels of diabetic mice were elevated early in the disease, as compared to control mice (200 ± 6 vs. 130 ± 7 mg/dl, respectively), and the mean level remained elevated throughout the period of observation.

Ludvigsson, J.; Säfwenberg, J.; Heding, L.

doi: 10.1007/BF00996321pmid: 838199

125 13 13 1 1 J. Ludvigsson J. Säfwenberg L. G. Heding Departments of Paediatrics Linköping University Linköping Blood Centre University of Uppsala Uppsala Sweden Novo Research Institute Copenhagen Denmark Summary HLA-types were determined in 102 juvenile diabetics. HLA-B8 was found in 39 patients (RR 2.64; p < 0.01) and HLA-BW15 in 32 patients (RR 1.33; n.s.). HLA-B7 was found in 14 patients (RR 0.40; p < 0.05). There were no correlations between HLA-B8 or BW15 and family history of diabetes, occurrence of infection before onset of diabetes, ketonuria at onset or the age at onset of diabetes. Serum C-peptide, insulin binding capacity of IgG and total serum insulin, IRI, were determined in 94 patients who had had diabetes for more than two years and who were beyond the remission period. Measurable amounts of C-peptide were found in 33 patients (34.7%). There was no evidence of a relationship between any particular HLA-antigen and the B-cell function except for an increased incidence of detectable C-peptide in patients with HLA-B18 and a tendency to a decreased incidence of detectable C-peptide in patients with the combination HLA-B8, W15. Only four patients (4.3%) were lacking insulin antibodies. HLA-BW15 positive patients had higher levels of insulin antibodies than other groups, while HLA-B7 positive patients had lower levels. The results suggest that HLA-B7 and HLA-B 18 might be associated with a different and perhaps milder form of juvenile diabetes.

Turner, R.; Hart, G.; London, D.

doi: 10.1007/BF00996322pmid: 190075

125 13 13 1 1 R. C. Turner G. Hart D. R. London Nuffield Department of Clinical Medicine Radcliffe Infirmary Oxford Queen Elizabeth Hospital Edgbaston Birmingham England Summary Basal insulin secretion has been thought to be via a different mechanism from stimulated insulin secretion, partly because it is not similarly suppressed by adrenalin. However, adrenalin normally causes hyperglycaemia, but if it is infused while the plasma glucose is kept constant there is marked suppression of insulin secretion. Sympathetic stimulation modulates basal insulin secretion, and alpha adrenergic blockade impaired the suppression of insulin secretion in response to hypoglycaemia. Four of five benign insulinomas had marked suppression of insulin secretion by adrenalin, but one malignant and one benign insulinoma had little suppression. Both had a raised proportion of their basal plasma insulin as proinsulin, and the impaired suppression of secretion by adrenalin probably signified an undifferentiated tumour.

Coleman, D.; Burkart, D.

doi: 10.1007/BF00996323pmid: 838200

125 13 13 1 1 D. L. Coleman D. L. Burkart The Jackson Laboratory Bar Harbor Maine USA Summary Plasma corticosterone concentrations in diabetic ( db ) mice maintained on two different inbred backgrounds were found to be elevated significantly when compared to normal controls. These data are similar to that reported with the phenotypically similar obese ( ob ) mouse. These results suggest that the hyperadrenolcorticism is not related to the primary gene action of either gene but rather is a consequence of the development of the obesity-diabetes syndromes.

Gepts, W.; Mey, J.; Marichal-Pipeleers, M.

doi: 10.1007/BF00996324pmid: 320079

125 13 13 1 1 Prof. Dr W. Gepts J. De Mey M. Marichal-Pipeleers Department of Pathology Vrije Universiteit Brussel Belgium Queen Elisabeth Medical Foundation Brussels Belgium Universitair Ziekenhuis Brugmann Van Gehuchtenplein 4 B-1020 Brussels Belgium Summary The cellular composition of the pancreatic islets of juvenile diabetics was studied, using recently developed immunocytochemical methods. B-cells were identified only in juvenile diabetics with a disease of short duration. In chronic juvenile diabetics, the islets which are classically viewed as “atrophic”, were shown to be composed of glucagon- and of somatostatin-cells. Another type of islets which commonly occurs in the pancreas of juvenile diabetics, i. e. the ribbon-like type first described by Cecil in 1911, appeared to be composed almost exclusively of “pancreatic polypeptide” (HPP)-cells. It is suggested that hyperplasia of the HPP-cells in the pancreas of juvenile diabetics results from an atypical type of islet regeneration induced by a severe and prolonged injury to the pancreatic endocrine tissue.

Nobel, E.; Laar, A.; Benraad, Th.

doi: 10.1007/BF00996325pmid: 838201

125 13 13 1 1 E. de Nobel A. van 't Laar Th. J. Benraad Department of Internal Medicine, Radboud Ziekenhuis University of Nijmegen Nijmegen The Netherlands Summary Early insulin responses were measured after a high dose (50 g/1.73 m 2 ) of rapidly injected glucose in 31 subjects who had repeatedly shown “lagstorage” curves in the OGTT, in 24 controls and in 19 mild maturity-onset diabetics. Division between controls and diabetics was virtually complete, when the insulin responses were expressed as “insulindgenic index” Twenty out of 31 patients with lag curves showed normal early insulin responses and 11 patients showed diabetic responses. In patients with lag curves, presence of obesity, and absence of family history of diabetes were associated with normal insulin responses. It is concluded that the finding of a lag curve is of little consequence in obese persons but, when in conjunction with a genetic background of diabetes, is suggestive of diabetes.

Gundersen, H.; Østerby, R.

doi: 10.1007/BF00996326pmid: 838202

125 13 13 1 1 H. J. G. Gundersen Dr. R. Østerby Second University Clinic of Internal Medicine and the University Institute of Pathology University of Aarhus Åarhus Denmark Department of Pathology Kommunehospitalet DK-800 Åarhus C Denmark Summary A study of autopsy kidney material from six long-term diabetics and four controls was performed in order to elucidate the mechanism of the glomerular enlargement in long-term diabetics. The volume and the severity of the glomerular lesion were measured in each of a number of randomly selected, open glomeruli. The relative amount of solid material was taken as an expression of the severity of the glomerular lesion. In the long-term diabetics the volume of open glomeruli was almost doubled compared to that of controls and in the individual subject the enlargement was found to be inversely related to the relative amount of solid material in the glomeruli. This indicates that the enlargement of open glomeruli in long-term diabetics is due to a compensatory hypertrophy rather than to the excessive deposition of basement membrane material. The number of nuclei per open glomerulus was increased in long-term diabetics, but nuclear size was unchanged. Most of the long-term diabetics had a large number of occluded glomeruli, and the individual, relative number of such glomeruli correlated closely both with the duration of diabetes above 15 years and the concentration of creatinine in serum. It is concluded that the destruction of glomeruli due to diabetic microangiopathy is compensated for some years by hypertrophy of the least affected glomeruli. This compensatory hypertrophy of glomeruli might well account for the preservation of renal function in long-term diabetics for a number of years despite the progressive basement membrane lesions of diabetic microangiopathy.

Hellman, B.; Lenzen, S.; Sehlin, J.; Täljedal, I.

doi: 10.1007/BF00996327pmid: 190076

125 13 13 1 1 B. Hellman S. Lenzen J. Sehlin I. -B. Täljedal Department of Histology University of Umeå Umeå Sweden Summary The uptake of 45 Ca 2+ by a lanthanum-nondisplaceable pool in pancreatic islets was studied. Raising the extracellular D-glucose concentration from 3 to 20 mM stimulated the 45 Ca 2+ uptake in hand-dissected islets of ob/ob-mice as well as in collagenase-isolated islets of ob/ob or normal mice. The effect was dose-dependent in the range of 0–20 mM D-glucose and was seen throughout a wide range of extracellular calcium concentrations (16 μmol — 2.56 mmol of Ca 2+ added per litre of medium). The 45 Ca 2+ uptake was also enhanced by other known insulin secretagogues (D-mannose, L-leucine, tolbutamide) and was uninfluenced by compounds lacking insulinreleasing capacity (3-O-methyl-D-glucose, L-glucose, D-galactose, D-leucine). The stimulatory effect of D-glucose was blocked by inhibitors of glucoseinduced insulin release (D-mannoheptulose, diazoxide, L-adrenaline). The results support the view that the lanthanum-nondisplaceable calcium pool is related to the insulin-releasing mechanism, although the exact nature of this relationship is still unclear.

Muller, W.; Aoki, T.; Egdahl, R.; Cahill, G.

doi: 10.1007/BF00996328pmid: 838203

125 13 13 1 1 W. A. Muller T. T. Aoki R. H. Egdahl G. F. Cahill Jr. Elliott P. Joslin Research Laboratory, Harvard Medical School, Dept. of Surgery Boston, University Medical Center Boston MA USA Institut de Biochimie Clinique University of Geneva Geneva Switzerland Summary Exogenous glucagon or epinephrine were infused into normal overnight fasted dogs to raise circulating hormone levels to concentrations within the physiologic range. Plasma levels of glycerol and free fatty acids remained unchanged during the glucagon infusion, but rose significantly during the administration of epinephrine. Plasma insulin in the systemic circulation remained unchanged during the glucagon infusion and increased slightly during the infusion of the catecholamine. The data suggest that in normal dogs glucagon in physiological amounts has no lipolytic effect. The importance of the sympathetic nervous system in regulating lipolysis in normal mammals is stressed.