bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethanol-induced Alterations of Glucose Tolerance, Postglucose Hypoglycemia, and Insulin Secretion in Normal, Obese, and Diabetic Subjects
Authors: Nikkilä Esko A , Taskinen Marja-Riitta 
Published: September 2013

Ethanol at an average blood concentration of 1 mg. per milliliter enhanced the immediate (first-phase) and prolonged (second-phase) insulin response to an intravenous glucose load in nonfasting normal human subjects. Simultaneously, the glucose disposal rate was increased and the postglucose hypoglycemia was accentuated, resulting in definite hypoglycemic symptoms in some individuals. Oral glucose tolerance was not changed by ethanol administration, but the thirty-minute blood glucose and plasma insulin values were increased, suggesting that alcohol might accelerate the absorption of glucose from the gut. Ethanol given orally during evening hours (1.5 gm. per kilogram) caused a nocturnal hyperinsulinemia and a decrease of blood glucose, but not an actual hypoglycemia. Oral glucose tolerance and plasma insulin response tested the next morning, when ethanol had disappeared from the blood, were not influenced by drinking the previous evening. The K-value of intravenous glucose was increased at this time, however. When alcohol was administered for one week at a dose corresponding to 25 per cent of daily calories and substituting for fat, both the oral and intravenous glucose tolerances were impaired in each subject but the insulin response remained unchaged.
In obese nondiabetic subjects, ethanol did not potentiate the early insulin response to intravenous glucose but it increased the second phase of insulin secretion in response to sustained hyperglycemia. In contrast to conditions in nonobese subjects, the glucose disposal rate was not incresed and postglucose hypoglycemia was not accentuated by ethanol in overweight subjects. In insulin-deficient diabetic patients the absent early insulin response could not be restored by ethanol, and the late component of insulin release was little increased by alcohol infusion. Ethanol did not improve the glucose utilization of diabetic patients.
Insulin Degradation by Isolated Fat Cells and their Subcellular Fractions
Authors: Hammond James M , Jarett Leonard 
Published: September 2013

Isolated frt cells and purified subcellular fractions of fat cells have been shown to degrade insulin to biologically inactive trichloroacetic-acid-soluble fragments. Further study of this activity has revealed the following characteristics:
1. Most of the insulin-degrading enzymes are intracellular, inaccessible to insulin or trypsin when fat cells are intact. More that 90 per cent of the recovered activity is found in the high-speed supernatant (cytosol) when cell fractionation studies are performed.
2. The plasma membrane contains significant insulin-degradative capacity, as shown by tryptic digestion of intact cells and cell fractionation.
3. The pH optimum of the cell-membrane insulin-degrading site is more acid than that of the cytosol activity, but the tow enzyme systems are similar with regard to substrate specificity, response to metabolic inhibitors, and elution volume of degradation products on gel filtration.
4. The plasma-membrane-degrading activity differs from the specific insulin-binding site with regard to saturation kinetics, optimum temperature, substrate specificity, sensitivity to sulfhydryl-blocking agents, and trypsin snesitivity.
Short-Term Treatment of Alloxan-Diabetic Rats with Intrajejunal Administration of Water-in-Oil-in-Water Insulin Emulsions
Authors: Shichiri Motoaki , Kawamori Ryuzo , Yoshida Michio , Etani Nobuaki , Hoshi Mitsuru , Izumi Kanji , Shigeta Yukio , Abe Hiroshi , Osaka Kanji 
Published: September 2013

Alloxan-diabetic rats with fasting blood glucose levels above 300 mg./100 ml. were treated with intrajejunal administration of water-in-oil-in-water (W/O/W) insulin emulsions via an indwelling catheter at a dose of either 25 or 50 U./100 gm. body weight, three times daily for five to fourteen days. The course of diabetes was followed by determinations of glucose levels in blood and urine.
During treatment a significant reduction in urinary glucose levels was observed in all rats studied. In two rats treated with 25 U./100 gm., fasting blood glucose levels did not change significantly. In four of five rats treated with 50 U./100 gm., W/O/W insulin emulsions significantly lessened hyperglycemia during treatment. Quantitative estimates suggested that the effectiveness of 50 U./100 gm. of intrajejunal W/O/W insulin emulsions was comparable to that after intramuscular regular insulin at doses between 1 and 2 U./100 gm.
These results would indicate that diabetes can be controlled by enteral administration of insulin preparations.
Insulin Sensitivity of the Large Human Adipocyte in Vitro
Authors: Davidson Mayer B 
Published: September 2013

Adipose tissue from twelve normal-weight and ten obese subjects on weight-maintaining diets and nine obese subjects on hypocaloric diets was removed at surgery and incubated in vitro. Basal glucose oxidation correlated significantly (r = 0.68, p &lt; 0.005) with fat-cell diameter in subjects on weight-maintaining diets. This relationship was significantly altered (p &lt; 0.02) in subjects on calorie-restricted diets. In tissue from subjects on weight-maintaining diets, physiologic concentrations of insulin (25 μU./ml.) significantly increased glucose incorporation into carbon dioxide (p &lt; 0.005) and glycogen (p &lt; 0.001). Maximum insulin-stimulated glucose oxidation (increase over basal) was significantly enhanced (p &lt; 0.05) in tissue from obese subjects, whereas insulin-mediated glucose incorporation into glycogen was similar in controls and obese subjects on weight-maintaining diets. Insulin-stimulated glucose oxidation was imparied in tissue from subjects on hypocaloric diets although fat-cell diameter was similar to those of obese subjects on weight-maintaining diets.
The effect of insulin on glucose incorporation into glycogen in isolated adipocytes was also studied. There was no correlation between insulin-stimulated glycogen synthesis and cell diameter. When cells from the same individual were separated into small and large adipocytes by differential flotation, the insulin effect was similar whether expressed as absolute or per cent increase over basal.
These results indicate that in vitro glucose oxidation by adipose tissue, in both the absence and the presence of insulin, is largely determined by dietary factors. This may also be true for insulin-stimulated glycogen synthesis. No evidence is provided for the concept that the enlarged human fat cell of obesity is insensitive to insulin in vitro.
Perspectives in Current Diabetes Research
Authors: Cahill George F 
Published: September 2013

The Thirteenth Research Symposium, sponsored by the American Diabetes Association in cooperation with itsits Indiana Affiliate and the University of Indiana School of Medicine, attracted an all-time high attendance of 227 research scientists, clinicians, and academicians to the Eli Lilly Center in Indianapolis, October 16 and 17, 1975.
Co-directors of the Symposium were John A. Galloway, M.D., of the University of Indiana School of Medicine, Philip Felig, M.D., of Yale University School of Medicine, and Gerold M. Grodsky, Ph.D., of the University of California, San Francisco.
Cell Membrane Changes in Chronically Diabetic Rats
Authors: Chandramouli V , Carter James R 
Published: September 2013

We have examined the effect of chronic diabetes mellitus upon cell membrane composition and turnover in streptozotocin-treated rats and control animals maintained for four to eight weeks. Liver plasma membranes, prepared from diabetic animals, showed enhanced activities of alkaline phosphatase and glucose-6-phosphatase and depressed 5'-nucleotidase when compared with controls. Studies of the nonprotein constituents of liver plasma membranes and red cell “ghosts” showed similar changes in both tissues: sialic acid and cholesterol content were reduced in the membranes of diabetic animals, while phospholipids (total and individual classes) and neutral sugars were unchanged.
To look for changes in relative turnover rates of individual membrane proteins, we combined a double-label in-vivo technic using [3H] and [14C] leucine with polyacrylamide gel separation of membrane proteins. No significant differences were observed between control and diabetic animals.
In chronically diabetic animals, cell membranes may show significant changes in overall composition with no significant changes in the rate of protein turnover.
Multiple Metabolic Functions of Glucose in Rat Pancreatic Islets
Authors: Pace Caroline S , Ellerman Jeanette , Hover Barbara A , Stillings Susan N , Matschinsky Franz M 
Published: September 2013

Metabolic interactions between glucose and amino acids were studied with isolated rat islets using glucose utilization and lactate formation as indicators. Certain amino acids (8–10 mM) are capable of greatly stimulating lactate formation from 5 mM glucose. On a molar basis L-isoleucine is the most potent stimulator in a group of twenty-six amino acids. A physiological amino acid mixture (7.5–14 mM) or L-isoleucine (8 mM) profoundly altered the basic sigmoidal relation between glucose concentration in the medium and the rate of glucose utilization and lactate formation: with basal glucose (5 mM) both glucose utilization and lactate production were stimulated by the amino acid mixture and by L-isoleucine; at high glucose levels utilization was decreased by the amino acid mixture, but was unaffected by L-isoleucine, whereas lactate formation was decreased by both additions. The data indicate that amino acids may play a significant role in regulating the extent to which glucose serves as a fuel of pancreatic islet cells and in determining the pathways of glucose metabolism.
In order to elucidate the mechanisms of the amino acid effect, studies with phloridzin, ouabain, iodoacetate, cytochalasin B, and Na±deficiency were performed with the most effective amino acid, L-isoleucine. Each of these agents and Na±deficiency substantially reduced or completely blocked the extra lactate formation induced by L-isoleucine (8–10 mM). The intracellular uptake of 14C L-isoleucine by isolated islets was found to be Na±independent, and uphill transport of this amino acid was not detectable, whether basal glucose was present in the medium or not.
The action of iodoacetate in blocking glycolysis was reinvestigated. After forty-five minutes of exposure, 0.2 mM iodoacetate completely blocks lactate formation as well as glucose utilization. This confirms and extends earlier data from this laboratory and suggests that this SH-reagent indeed allows dissociation of the fuel and releasing functions of glucose.
Norepinephrine, Epinephrine, and Dopamine Contents of the Cardiovascular System in Long-term Diabetics
Authors: Neubauer B , Christensen N J 
Published: September 2013

Norepinephrine, epinephrine, and dopamine concentrations were studied in the cardiovascular system of postmortem material obtained from six long-term diabetics and six control subjects.
Norepinephrine concentration was considerably reduced in the cardiovascular system of the diabetic patients. The mean norepinephrine concentration in the apex of the heart, the radial artery, the posterior tibial artery, and the femoral artery in the diabetics averaged 6, 9, 12, and 20 per cent, respectively, of the corresponding mean values in the controls.
Epinephrine was present in the cardiovascular system in the controls but in small amounts in comparison with norepinephrine. There was no correlation between the epinephrine and the norepinephrine concentrations in the tissue. In the diabetics the epinephrine concentration in the heart and in the arteries did not differ from the values obtained in the controls.
The dopamine concentration averaged 11 per cent of the norepinephrine concentration in the cardiovascular system in the controls. There was a strong correlation between tissue concentrationsof dopamine and of norepinephrine. In the diabetics the dopamine concentration was reduced, but relatively less than that of norepinephrine, and constituted 53 per cent of the norepinephrine concentration.
It is suggested that the depletion of the norepinephrine stores in the heart in diabetic patients may in part be responsible for their reduced survival rate in acute myocardial infarction.
Growth Hormone Stimulating the Growth of Arterial Medial Cells in Vitro: Absence of Effect of Insulin
Authors: Ledet Thomas 
Published: September 2013

Earlier studies have shown a stimulatory effect of diabetic serum on the growth of rabbit aortic medial cell cultures.
Growth media supplemented with normal serum with added insulin (50-2,000 μU./ml. serum) did not enhance the growth of the medial cell cultures. Control media containing serum from recent diabetics with low insulin concentration stimulated the growth (2p &lt; 0.01).
Supplementation of normal serum with human growth hormone (final concentration 1-5 ng./ml. medium) resulted in a significant enhancement of growth (2p &lt; 0.005). The growth-promoting effect of growth hormone was not detectable with lower concentrations (0.5 ng. and 0.1 ng./ml. medium).
The growth effect of the low concentration of growth hormone could not be augmented by increasing the concentration of glucose in the incubation medium.
Growth hormone in an amount of 1 ng./ml. medium increased both the number of 3H-thymidine-labeled cells as identified by autoradiography and the number of mitotic bodies (2p &lt; 0.005 and 2 p &lt; 0.025).
The present results demonstrate that the growth-stimulating factor(s) in diabetic human serum described earlier is not insulin but may well be growth hormone.
Treatment of Insulin-induced Lipoatrophy
Authors: Hulst S G Th 
Published: September 2013

Twenty children with insulin-induced lipoatrophy were successfully treated by injecting the insulin into the lipoatrophic area. In 10 children insulin therapy was replaced by monocomponent insulins, while the other 10 children were treated with the insulins they previously used.
It is concluded that both monocomponent and less purified insulins are suitable for treating the complication of insulin therapy when the insulin is injected into the lipoatrophic area.
Continuous Extracorporeal Monitoring of Animal Blood Using the Glucose Electrode
Authors: Layne E C , Schultz R D , Thomas L J , Slama G , Sayler D F , Bessman S P 
Published: September 2013

A continuous extracorporeal monitoring system for blood glucose employing an electrochemical sensor is described. The sensor, about the size of a nickel, is rapid, is specific for glucose, generates its own power, and consists of two galvanic oxygen electrodes. Over one oxygen electrode is affixed a plastic matrix to which glucose oxidase is covalently bound; a blank matrix is over the other, which serves as a reference. Oxygen is consumed in the glucose-oxidase-containing matrix, decreasing the current from the underlying oxygen electrode. The current decrease is nonlinearly proportional to the glucose concentration.
The sensor is clamped between small blocks of plastic fitted with inlet and outlet nipples so that blood pumped from the animal passes over the two electrodes and thence to an automated chemical analysis for comparison. Blood is collected and anticoagulant added in a double-lumen catheter. Blood is withdrawn at the rate of 1 cc. per hour.
Results obtained by use of the system in rabbits are reported. The capacity of the system to continuously monitor changes in blood glucose produced by repeated glucose tolerances is shown in hypo-, normo-, and hyperglycemic animals. Some properties of the system and its calibration are discussed.
Insulin degradation: XVI. Evidence for the Sequential Degradative Pathway in Isolated Liver Cells
Authors: Varandani Partab T , Nafz Mary Ann 
Published: September 2013

Isolated liver cells contain insulin-degrading activity. Examination by chromatography on Sephadex G-75 of the products formed from 125I-insulin (1 nM or 1 µM) upon incubation with suspensions of hepatocytes for various time periods showed that there is at first a transient accumulation of the intermediate product, A chain, which is further hydrolyzed by protease(s) to low-molecular-weight components. These results indicate that the sequential degradative pathway is operative, both at low and high concentrations of insulin, in isolated liver cells, i.e., the insulin is first split at the disulfide bonds by glutathione-insulin transhydrogenase (GIT) into A and B chains, followed by proteolysis of the resultant polypeptides, and that this system might be used for well-defined studies of factors controlling insulin metabolism.
The chelating agent ethylenediamine tetraacetic acid (EDTA) accelerated the accumulation of A chain (i.e., enhanced the activity of GIT), which is in keeping with its effect with purified GIT. In contrast to previous studies with tissue homogenates in which EDTA caused a marked inhibition of the proteolytic stage, EDTA had little or no effect with intact liver cells. Since EDTA does not appreciably penetrate the cell membrane, these data suggest that GIT activity either occurs on the cell surface or is readily available at the cell surface, whereas the proteolytic activity either occurs inside the cell or is inaccessible at the cell surface.
Isotransplantation of Organ-Cultured Neonatal Pancreas: Reversal of Alloxan Diabetes in the Rat
Authors: Hegre O D , Leonard R J , Schmitt R V , Lazarow A 
Published: September 2013

Pancreases from neonatal rats four to 16 days postpartum were grown in organ culture for from two to nine days. Approximately 10-20 explants, each measuring 1 mm.3 (1 mg.), were grown on a single Millipore filter placed at the gas-liquid interface of a medium consisting of 50 per cent horse serum and 50 per cent chick embryo extract. Following organ culture, an estimated 9-20 mg. of cultured islet tissue were dissociated with collagenase and isotransplanted into the peritoneal cavity of alloxan-diabetic recipients.
In seven of eight recipients the diabetes was reversed between 11 and 53 days of posttransplantation. Animals receiving 12-16 mg. of cultured islet attained normoglycemia in 11-20 days; animals receiving 9-10 mg. of cultured islet tissue recovered between 45 and 53 days. These animals have remained symptom-free for over six months.
Biopsies of grafts taken from the peritoneal cavity following reversal of diabetes contained well-vascularized islets compared primarily of heavily granulated beta cells. Quantitative analysis of host pancreases by the linear scanning method (biopsied at one to two weeks and four to five months following reversal of the diabetes) demonstrated that the total beta-cell mass was 3 per cent and the total insulin content was 6 per cent of the normal values. Little or no evidence of regeneration of host beta cells was observed.
These studies show that a period of organ culture prior to isotransplantation does not impair the ability of islet tissue to reverse alloxan diabetes in the rat.
Phenformin-associated Metabolic Acidosis
Authors: Fulop Milford , Hoberman Hemry D 
Published: September 2013

We report 18 consecutive phenformin-treated diabetic patients admitted to this Medical Service acutely ill with metabolic acidosis. Lactic acidosis was anticipated, and documented, in all. Also, however, though most of the patients had only weakly positive, or even negative, serum reactions with the nitroprusside reagent, all were found to have coexisting ketoacidosis, plasma 3-hydroxybutyrate averaging 7.1 mmol/L. ± 3.9 (S.D.). This finding suggest that treatment of these patients should include insulin, and often also glucose, because most do not have marked hyperglycemia and some have hypoglycemia.
The lactic acidosis in the nine patients who survivied was, on average, less severe than in the nine who died, but the difference was not statistically significant. Surivival correlated closely with the absence of shock on arrival.
Only eight patients had a identifiable acute illness other than the metabolic acidosis. The other 10 patients had no discernible cause for the acute illness apart from their treatment with phenoformin. This finding raises serious doubts about whether phenformin should be used to treat patients with diabetes.
Altered Lysosomal Glycohydrolase Activities in Juvenile Diabetes Mellitus
Authors: Bomback Fredric M , Nakagawa Sachiko , Kumin Selma , Nitowsky Harold M 
Published: September 2013

Studies have been carried out on activities of lysosomal β-N-acetylhexosaminidase (hex), β-galactosidase (β-gal), α-glucosidase (α-glu), and acid phosphatase (AP) in serum and urine from patients with juvenile diabetes and matched controls. There is a large increase in blood and urinary hex activity (the former presenting three distinct patterns of abnormality), a moderate increase in urinary β-gal, and a small increase in urinary α-glu activity, but no elevation of blood or urinary AP in the diabetics. Urinary α-glu activity in the diabetics shows striking inhibition by glucose, and this may reflect a similar phenomenon in vivo.
Although glycohydrolase activities are elevated in patients with no detectable microangiopathy, more striking changes may be observed in patients with severe small-vessel disease. These alterations may be associated with increased glycoprotein catabolism in the diabetic, an area in need of further studies in the human and experimental diabetic animal.
Hyperlipoproteinemia in Streptozotocin-treated Rats
Authors: Bar-On Hanoch , Roheim Paul S , Eder Howard A 
Published: September 2013

In order to study hyperlipidemia in diabetes mellitus, rats were made diabetic by administration of streptozotocin and the optimal conditions for production of severe and persistent hyperlipoprotenemia determined. Two groups of rats were compared: rats fed sucrose-rich diets and rats fed laboratory chow. The optimal dose of streptozotocin was 45 mg/kg body weight for the sucrose-fed rats. With this dose, plasma glucose reached a maximum of over 600 mg./100 ml., and plasma insulin was reduced by 60 per cent. Plasma triglycerides rose in the sucrose-fed rats to over 1,000 mg/100 ml. two days after the streptozotocin was given and then decreased to over 770 mg./100 ml. 12 days after treatment and then to 585 mg./100 ml. 10 weeks after induction of diabetes. With this dose, ketonuria did not occur nor did any of the animals die, as occurred with higher doses. In the chow-fed rats, plasma triglyceride levels were elevated with the induction of diabetes to levels of approximately 300 mg./100 ml.
The concentration of all the plasma lipoproteins increased with the induction of diabetes. The concentration of very-low density lipoprotein (VLDL) protein in the sucrose-fed diabetic increased fivefold, the low-density lipoprotein (LDL) protein increased, and especially striking was the increase in high-density lipoprotein (HDL) protein concentration, which became more pronounced with the duration of the diabetes. The diabetes produced by streptozotocin administration to sucrose-fed rats, thus, provides a useful model for the study of the hyperlipoproteinemia of diabetes.