Diabetologia

Martin, F.; Russell, J.

doi: 10.1007/BF01219662pmid: 4844184

125 10 10 2 2 F. I. R. Martin J. Russell Departments of Endocrinology and Biochemistry Royal Melbourne Hospital Melbourne Australia Summary A simple method for the estimation of plasma insulin in the presence of insulin antibodies is described using dilution and dextran-charcoal separation. In 43 non-insulin resistant diabetics the estimated non-extracted (N.E.) insulin was between 69 and 2444 μU/ml. N.E. insulin appears to be constantly related to values obtained by acid-alcohol extraction of plasma containing insulin-antibodies, representing about 60% of total insulin.

Gibson, T.; Fuller, J.; Grainger, S.; Jarrett, R.; Keen, H.

doi: 10.1007/BF01219663pmid: 4844185

125 10 10 2 2 T. Gibson J. H. Fuller S. L. Grainger R. J. Jarrett H. Keen Unit for Metabolic Medicine, Department of Medicine Guy's Hospital SE 1 9RT London Great Britain Summary The inter-relation between hypertriglyceridaemia and glucose intolerance has been studied experimentally in fifteen male subjects by measuring the effect of acute elevation of plasma triglyceride (injection of Intralipid intravenously) upon oral glucose tolerance. The induced hypertriglyceridaemia did not alter the mean blood glucose or plasma insulin response to oral glucose. The associations between plasma triglyceride levels and glucose tolerance observed both in general population studies and in “patient” populations are probably due to a mutual link with a further factor or factors.

Weeke, J.; Hansen, Aa.

doi: 10.1007/BF01219664pmid: 4210708

125 10 10 2 2 J. Weeke Aa. Prange Hansen Second University Clinic of Internal Medicine Kommunehospitalet Aarhus Denmark Summary Serum thyrotropin (TSH) and growth hormone (GH) were measured in 24 women and 25 men with juvenile diabetes and in comparable normals. Samples were obtained in the postprandial state at 11 a.m., during a 24 h period of daily life and after thyrotropin releasing hormone (TRH) stimulation. The diurnal TSH rhythm in the diabetics was similar to that found in normals. The TSH values at the nadir of the diurnal TSH rhythm (11 a. m.) were identical in diabetics and normals; in addition there was no difference in the TSH response to TRH. No sex dependent difference of the basal TSH level or of TSH response to TRH was present. Serum GH was higher in women than in men, and higher in diabetics than in normals. The study indicates that diabetes mellitus is not likely to be a disease accompanied by a generalized hypo-thalamic dysfunction.

Gliemann, J.; Gammeltoft, S.

doi: 10.1007/BF01219665pmid: 4367434

125 10 10 2 2 Dr. J. Gliemann S. Gammeltoft Institute of Medical Physiology C University of Copenhagen 71, Rådmansgade DK-2200 Copenhagen N. Denmark Summary A number of modified insulins were assayed for biological activity (increase in synthesis of lipids from glucose) and binding affinity (inhibition of receptorbinding of 125 I-insulin) on rat fat cells and the following was found: -1. The modified insulins tested showed the same maximal effect as native insulin. Decrease in biological activity induced by modifications was interpreted as decrease in potency. -2. Removal of 2 amino acids from the amino-terminal end of the B chain caused little or no decrease in potency. Removal of 5 amino acids from the carboxy-terminal end of the B chain caused a decrease in potency to about 17% of that of insulin. Removal of one amino acid (glycine) from the amino-terminal end of the A chain caused a decrease in potency to about 1 %. -3. Substitutions with acetyl or succinyl residues at position Al had a greater effect on the potency than substitution at position B1 or B29. -4. Cross linkage between positions A1 and B29 caused decreases in potency on fat cells to between 2 and 10%. Cross linkage between positions A1 and B1 almost abolished biological activity. −5. 9 of the modified insulins were tested for ability to inhibit binding of 125 I-insulin to fat cell receptor sites. The decrease in receptor binding affinity induced by chemical modifications was, in all cases, in agreement with the decrease in biological potency.-6. It is concluded that the binding affinity of insulin to the receptor, and therefore the potency, is dependent on (1.) a largely unchanged tertiary structure of the insulin molecule and (2.) free access to the region of the amino-terminal end of the A chain.

Perrett, A.; Rowe, A.; Shahmanesh, M.; Allison, S.; Hartog, M.

doi: 10.1007/BF01219666pmid: 4844186

125 10 10 2 2 A. D. Perrett A. S. Rowe M. Shahmanesh S. P. Allison M. Hartog Bristol Royal Infirmary University Department of Medicine Bristol England Summary Blood lipid estimations were performed on 118 diabetics receiving different forms of treatment and with varying degrees of control of their diabetes. Elevated blood lipids were found predominantly in elderly patients being treated with hypoglycaemic drugs and could not be accounted for by poor diabetic control. Patients with elevated plasma triglycerides were significantly heavier than those with normal levels.

Kissebah, A.; Adams, P.; Wynn, V.

doi: 10.1007/BF01219667pmid: 4844187

125 10 10 2 2 A. H. Kissebah P. W. Adams V. Wynn Alexander Simpson Laboratory for Metabolic Research St. Mary's Hospital Medical School W. 2 London Summary The plasma free fatty acid and triglyceride transport kinetics in 16 non-obese and 7 obese maturity onset diabetics with hypertriglyceridaemia have been compared with results obtained in 27 control subjects. Changes in glucose and insulin responses were evaluated in relation to the lipid parameters. All the diabetics showed elevated plasma FFA levels and turnover rates. In the non-obese diabetics the plasma triglyceride turnover rate was within the normal range and their hypertriglyceridaemia was due to impaired triglceride clearance. In the obese diabetics the plasma triglyceride turnover rate was increased and they also had some impairment of triglyceride clearance, so that in them a double mechanism was observed to account for their hypertriglyceridaemia. The insulin levels in the diabetics were similar to, or greater than, those found in the controls. Our results suggested that the enhanced lipolysis and impaired triglyceride clearance observed in the diabetic patients were a manifestation of insulin unresponsiveness in adipose tissue and that the changes in insulin and glucose relationship could be secondary to elevated FFA and triglyceride levels. Further confirmation was obtained by the finding of an exaggerated insulin response to a glucose challenge in normal subjects infused with Intralipid. Treatment with phenethylbiguanide (Phenformin) significantly lowered the plasma FFA and triglyceride concentration in both diabetic groups. This was associated with normalisation of both plasma FFA turnover and triglyceride clearance. It also reduced the triglyceride turnover rate to the normal range in the obese diabetics. These changes were associated with a fall of plasma glucose and insulin levels to within the normal range. These results suggested an effect of Phenformin in reducing the rate of lipolysis leading to improved glucose tolerance.

L'age, M.; Fechner, W.; Langholz, J.; Salzmann, H.

doi: 10.1007/BF01219668pmid: 4210709

125 10 10 2 2 M. L'age W. Fechner J. Langholz H. Salzmann Abteilung für Endokrinologie, Medizinische Klinik und Poliklinik, Klinikum Steglitz Freie Universität Berlin Federal Republik of Germany Summary Withholding of insulin therapy in alloxan diabetic rats results in a steady increase of plasma corticosterone, which is associated with a decrease in pH and bicarbonate and with an increase in plasma FFA and ketone bodies. Adrenalectomy prevents the development of ketoacidosis after withholding insulin therapy, whereas stimulation of the adrenal cortex accelerates the development of diabetic ketoacidosis. In insulin deficiency a stress signal produces significantly higher corticosterone levels when compared with normal rats. It is concluded that glucocorticoids are involved in the development of ketoacidosis in the insulin deficient rat.

Gilbert, C.; Kaye, J.; Galton, D.

doi: 10.1007/BF01219669pmid: 4844188

125 10 10 2 2 C. H. Gilbert J. Kaye D. J. Galton Diabetes Research Laboratory St. Bartholomew's Hospital London B.C.I. England Summary The release of fatty acids and glycerol from adipose tissue of obese diabetics and obese controls has been studied in relation to the fall in plasma fatty acids during a glucose tolerance test. Adipose tissue was taken at zero-time and lh after an oral glucose load (50g). Obese diabetics released more fatty acids from adipose tissue than obese controls ( p < 0.001), whereas glycerol release was similar in the two groups. The percent reduction in release of fatty acids from adipose tissue of obese diabetics during a G. T. T. was significantly less than obese controls (p < 0.02), as was the percent fall in plasma fatty acids (p < 0.02), whereas the percent reduction in glycerol release from adipose tissue was similar in the two groups. In addition the percent fall in plasma fatty acids during a G.T.T. correlated with the percent reduction in release of fatty acids from adipose tissue (p<0.05), but not with release of glycerol; and the increment in plasma insulin from zero-time to lh during a G.T.T. correlated with the percent reduction in fatty acid release from adipose tissue (p<0.01). Finally, the plasma insulin at lh of a G.T.T. correlated inversely with the release of fatty acids from adipose tissue (p<0.05), but not with the release of glycerol. The data is consistent with the view that the plasma fatty acids fall during a G.T.T. due to re-esterification of fatty acids rather than due to an antilipolytic action of insulin.

Molnar, G.; Taylor, W.; Langworthy, A.

doi: 10.1007/BF01219670pmid: 4844189

125 10 10 2 2 G. D. Molnar W. F. Taylor A. Langworthy Mayo Clinic and Mayo Foundation Rochester Minnesota Summary Individual blood glucose (BG) measurements at selected time points were compared with continuously recorded BG data as criteria of the adequacy of diabetes regulation. Indices reflecting the adequacy of diabetes regulation have previously been developed from continuously monitored BG measurements during studies under standardized near-normal living conditions. These indices are: (1) mean amplitude of glycemic excursions (MAGE), (2) diurnal mean blood glucose (MBG), (3) mean of daily differences of paired BG values (MODD). Because of the intensive studies necessary to obtain these indices, approximations based on individual BG measurements which might easily be obtained in practice were sought. The BG value 80 min after breakfast correlated best with the MAGE. The average of the fasting BG value and the value at 80 min after breakfast correlated well with the MBG. These individual BG measurements distinguished the groups of subjects. The difference between fasting BG values on successive days (AFBG) correlated well with the MODD. However, unlike MODD itself, AFBG did not distinguish the groups of subjects. Some other selected BG values with different timing were nearly equally highly correlated with these three criteria of BG behavior. Thus, relatively few but critically timed BG measurements on successive days, with suitable urinary glucose measurements, during standardized therapeutic programs may serve as an index of the efficacy of the therapy. By these same means, the characteristics of the patient's diabetes might also be assessed.

Iynedjian, P.; Peters, G.

doi: 10.1007/BF01219671pmid: 4844190

125 10 10 2 2 P. B. Iynedjian G. Peters Institut de Pharmacologie de l'Université de Lausanne Lausanne Switzerland Summary The hyperglycemic response to two 2-ml injections of guinea pig anti-insulin serum (GPAIS), given at a 1.5 h interval, was measured after 18 h of fast in nephrectomized rats, intact animals and animals with anuria caused by ligating the ureters. In controls plasma glucose rose by + 196±4.0 mg/100 ml within 1.5 h after G-PAIS injection, then levelled off with the onset of glucosuria and began to decline at 4.5 h. Anuria due to ureteral obstruction did not affect the initial rise of plasma glucose (+ 197±11.9mg/100ml at 1.5h). In contrast, the initial rise of plasma glucose amounted to only + 136± 5.3 mg/100 ml at 1.5h in nephrectomized rats. Blood sugar remained lower in the latter animals than in those with ligated ureters for the rest of the experiment. The blunted glycemic response to GPAIS in anephric rats, thus, is due to the loss of kidney tissue per se. It is suggested that, after sudden insulin deprivation, the kidneys might release sizeable amounts of newly synthesized glucose into the circulation.