bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin Metabolism in Hypothyroidism
Authors: Shah Jayendra H , Motto George S , Papagiannes Elaine , Williams Gerald A 
Published: September 2013

Insulin resistance has been invoked to explain the glucose intolerance observed in hypothyroid patients. This possibility was studied by determining fractional and metabolic clearances of intravenously administered porcine crystalline insulin (0.1 U./kg.) and its effect on plasma glucose concentration in ten hypothyroid patients, ten normal subjects, and six treated euthyroid patients.
Following administration of porcine insulin, serum immunoreactive insulin concentrations during the period of observation were similar in hypothyroid patients, in normal control subjects, and in treated euthyroid patients. Similarly, no significant differences in the mean half-life, distribution space, or fractional and metabolic clearances of insulin were observed among any of the three groups.
In response to insulin administration, plasma glucose concentrations declined to the nadir of 36 ± 4, 43 ± 3, and 38 ± 4 mg. per 100 ml. in hypothyroid patients, normal control subjects, and treated euthyroid patients, respectively. Thereafter, plasma glucose steadily increased and approached the baseline value at ninety minutes in normal subjects and treated euthyroid patients. In contrast, the plasma glucose values remained significantly lower than the baseline for the rest of the procedure in hypothyroid patients.
The present study demonstrates that there is no evidence of resistance to the action of insulin in hypothyroid patients. The observation of prolonged hypoglycemic action of exogenously administered insulin in hypothyroid patients might in fact suggest increased sensitivity to insulin action. These findings indicate that glucose intolerance of the hypothyroid state is not characterized by insulin resistance.
Modulation of Fatty Acid Metabolism by Glucagon in Man. III. Role of Pharmacologic Limitation of FFA Availability
Authors: Schade David S , Eaton R Philip 
Published: September 2013

This study was undertaken to examine the contribution of plasma free fatty acid availability upon the regulation of ketone body and endogenous triglyceride concentration in man. This substrate-product relationship was examined both in the basal state and during hormonally induced ketogenic stimulation.
Five insulin-deficient diabetics receiving a fixed dose of exogenous insulin were studied after a twelve-hour fast and twenty-four hours after their last therapeutic insulin injection. Reduction in basal free fatty acid concentration was induced with two weeks of clofibrate administration, and hormonal ketogenic stimulation was induced with glucagon administration.
A highly significant correlation was observed between the basal free fatty acid level and the basal ketone body concentration. This substrate-product relationship persisted throughout hormonally induced ketogenic stimulation, suggesting that the basal free fatty acid concentration is a major determinant of the plasma ketone body concentration in man. In contrast, alterations in basal free fatty acid concentration were not accompanied by consistent changes in plasma triglyceride concentration, suggesting that plasma free fatty acid concentration may not be the principal determinant of the endogenous triglyceride concentration in clofibrate-treated diabetic man.
Antidiabetic Action of Somatostatin–Assessed by the Artificial Pancreas
Authors: Meissner C , Thum Ch , Beischer W , Winkler G , Schröder K E , Pfeiffer E F 
Published: September 2013

By means of a glucose-controlled insulin- and glucose-infusion system (GCIGIS) we examined the effect of somatostatin on insulin and glucose requirements following meals or oral glucose loads in juvenile diabetics.
In six of seven patients the insulin requirement with somatostatin was remarkably reduced to between 38 per cent and 79 per cent of that of otherwise identical control experiments. No reduction could be found in the seventh case, fed only 575 kcal. In all cases we observed an increase in dextrose demanded from the GCIGIS ranging between 28 per cent and 192 per cent of the control amounts. In addition, a lowering and smoothing of postprandial blood glucose curves caused by somatostatin application was a general finding.
It seems to us most likely that the well-known suppression of the secretion of growth hormone and glucagon, both insulin antagonists, is responsible for the antidiabetic action of somatostatin.
Hormonal Regulation of Glycogen Metabolism in Human Fetal Liver: II. Regulation of Glycogen Synthase Activity
Authors: Schwartz Alan L , Rall Theodore W 
Published: September 2013

During the first two thirds of gestation, the concentrations of UDPG, ATP, ADP, and Mg++ in human fetal liver remain constant, whereas the concentration of Pi decreases twofold and the G-6-P and AMP concentrations increase. Incubation of human fetal liver explants with glucagon or insulin did not alter the concentrations of any of these intermediates.
ATP, ADP, and Pi are inhibitors of human fetal liver glycogen synthase D-form activity, while G-6-P and AMP and Mg++ are stimulators. Ca++ at concentrations of &lt; 0.1 mM was found to stimulate glycogen synthase D activity. This effect of Ca++ was also observed in “physiologic” mixtures containing UDPG, G-6-P, ATP, ADP, AMP, Pi, and Mg++ at concentrations found either in liver in utero or in explants. 45Ca++ efflux from perifused (rat) fetal liver explants was stimulated by glucagon. These data provide a picture of the metabolite regulation of human fetal liver glycogen synthase activity in which the D-form may largely control glycogen synthesis in utero and hormonal effects on glycogen synthase may be induced by effects of Ca++ on the D-form.
Plasma Renin Activity and Blood Volume in Uncontrolled Diabetes: Ketoacidosis, a State of Secondary Aldosteronism
Authors: Christlieb A Richard , Assal Jean-Philippe , Katsilambros Nicholas , Williams Gordon H , Kozak George P , Suzuki Tadao 
Published: September 2013

The renin-angiotensin-aldosterone system was evaluated in two types of uncontrolled diabetes: a) diabetic ketoacidosis, and b) nonketotic hyperglycemia. In thirteen patients with ketoacidosis, mean plasma renin activity (PRA) was 58 ± 12 (S.E.M.) ng. per milliliter per hour and in four patients, plasma aldosterone was 82 ± 17 ng. per 100 ml. Corresponding values for upright saltdepleted subjects were 13 ± 2 and 62 ± 8. In eleven diabetics with nonketotic hyperglycemia (mean glucose 318 ± 19 mg. per cent), mean blood volume was 4,660 ml. and PRA 2.1 ± .7. After control of the diabetes (mean glucose 129 ± 13) blood volume was 4,553 ml. and PRA 3.3 ± 1 (N.S.).
The results suggest that: 1) diabetic ketoacidosis is a state of severe secondary aldosteronism, 2) no significant change in blood volume or PRA occurs during short periods of hyperglycemia, and 3) insulin is not necessary for renin release.
Hyperinsulinemia and Enlarged Adipocytes in Patients with Endogenous Hyperlipoproteinemia without Obesity or Diabetes Mellitus
Authors: Bernstein Robert S , Grant Neville , Kipnis David M 
Published: September 2013

Studies of adipocyte metabolism were performed in twelve male subjects with normal plasma lipids and eleven male patients with Type IV or Type V hyperlipoproteinemia. Patients with obesity or diabetes mellitus were excluded from the study. Although all patients had normal glucose tolerance tests, the blood glucose levels during these tests were higher in the hyperlipoproteinemic patients than in the normal control subjects and the plasma insulin responses were even more strikingly elevated in the hyperlipemic group.
Adipocytes isolated from hypertriglyceridemic subjects were larger than those obtained from normal individuals and exhibited increased activities of both Type I and Type II hexokinase and increased rates of glucose oxidation and lipogenesis from glucose. Cell size, hexokinase isoenzyme activities and rates of lipogenesis from glucose were all strongly correlated with each other, but none of these measurements were correlated with glucose oxidation. It is not known how the adipocyte abnormalities are related to the lipid transport disorder.
Responses to Arginine of the Perfused Pancreas of the Genetically Diabetic Chinese Hamster
Authors: Frankel Barbara J , Gerich John E , Fanska Rudolph E , Gerritsen George C , Grodsky Gerold M 
Published: September 2013

Nonketotic, genetically diabetic Chinese hamsters show subnormal pancreatic insulin release and impaired suppression of glucagon in response to glucose.
To study the pancreatic effects of other agents, dynamic insulin and glucagon release was measured from the in vitro perfused pancreases of normal and diabetic Chinese hamsters in response to various combinations of arginine (20 mM), glucose (100 or 150 mg. per 100 ml.), and theophylline (10 mM).
Theophylline alone caused identical insulin and glucagon release in diabetics and normals. Glucose, alone and in the presence of theophylline, caused subnormal insulin release and less suppression of glucagon release in the diabetics than in the normals. Arginine, in the presence of glucose and theophylline, caused excessive glucagon release but nearly normal insulin release in the diabetics Arginine, in the absence of glucose or theophylline, caused excessive glucagon release in the diabetics and undetectable insulin release in either diabetics or normals. Pancreatic content after perfusion did not correlate with release during perfusion. Infusion of arginine alone markedly decreased the amount of extractable pancreatic insulin and glucagon.
These results indicate that the pancreatic alpha cell of the diabetic Chinese hamster responds excessively to arginine, as is seen in the human diabetic. This defect is not related to acute insulin release or the presence of glucose. Further, these results confirm that the diabetic Chinese hamster's alpha and beta cells respond normally to theophylline, but are relatively insensitive to glucose.
Dynamics of Tolbutamide, Glucose, and Insulin Interrelationships Following Varying Doses of Intravenous Tolbutamide in Normal Subjects
Authors: Ganda O P , Kahn C B , Soeldner J S , Gleason R E 
Published: September 2013

Four healthy adult subjects received intravenous tolbutamide (TOL) at six different doses (twenty-four tests): 0.0625 gin., 0.125 gin., 0.25 gm., 0.5 gin., 1.0 gm. and 1.5 gm. Blood glucose (BG), serum immunoreactive insulin (IRI) and serum TOL levels were determined before and for 180 minutes after TOL. There was a highly significant correlation of the dose of TOL with the peak IRI (p&lt;.01), zero to ten minute IRI area (p&lt;.001), and zero to sixty minute IRI area (p&lt;.001) and with the decline in BG expressed as zero to sixty minute BG area (p&lt;.001). Similar significant correlations were observed between levels of TOL and both IRI and BG. At each dose level the IRI response correlated significantly with the BG fall.
An additional eighteen subjects received the 1.0 gm. dose. In these, serum TOL levels did not correlate with either BG or IRI. These subjects also received intravenous glucose (0.5 gm. per kilogram body weight). BG levels did not correlate with IRI. However, there were striking correlations between TOL and glucosestimulated peak IRI (p&lt;.001), zero to ten minute IRI area (p&lt;.001) and zero to sixty minute IRI area (p&lt;.05). Also, the zero to ten minute BG areas in the two tests were negatively correlated (p&lt;.05).
The mean (± SEM) space of distribution for glucose (G.S.) and tolbutamide (T.S.) was found to be 13.45 ± 0.71 and 6.34 ± 0.31 L., respectively. There was a significant correlation between G.S. and T.S. (r = 0.70; p&lt;.01).
Within individuals a significant dose-response relationship exists between TOL and IRI. TOL- and glucose-induced IRI secretion dynamics suggest strong similarities between mechanisms of rapid IRI release and/or size of available IRI storage pools.
Degradation of Insulin by Isolated Rat Liver Cells
Authors: Le Cam Alphonse , Freychet Pierre , Lenoir Pierre 
Published: September 2013

The degradation of insulin by isolated rat liver cells has been studied. The phenomenon is time- and temperature-dependent. After sixty minutes' exposure to 1.5 × 106 cells/ml, about 50 per cent, 15 per cent, and less than 5 per cent of insulin at 1.5 μM. are degraded at 37° C., 20° C., and 0° C., respectively. The methods used to measure the hormone degradation affect the apparent Vmax. Higher values of Vmax are found when radioimmunoassay rather than precipitation by trichloracetic acid and adsorption to talc is used. However, the apparent Km. (0.27 μM.) is virtually the same with any of the methods used. N-ethyl-maleimide and Trasylol are potent inhibitors, whereas GSH increases the hormone degradation. Proinsulin acts as competitive inhibitor (apparent Ki = 0.35 μM.).
Gel filtration patterns of incubation supernates suggest that several enzymatic systems may be operative in the degradation of insulin by the liver cells. Glutathione-insulin-transhydrogenase is suggested by the appearance of a component that has the same elution volume as the A chain, but the inhibitory effects of trasylol on insulin degradation, as well as qualitative and quantitative similarities with insulin proteases, suggest that a proteolytic mechanism is involved. The insulin-degrading system in isolated liver cells closely resembles that observed in purified liver plasma membranes and in the isolated perfused liver. Such similarities stress the possible significance of the degradation process in the regulation of insulin action. These studies are also important for the quantitative analysis of insulin interaction with its specific receptors in isolated liver cells.
Hormonal Regulation of Incorporation of Alanine-U-14C into Glucose in Human Fetal Liver Explants: Effect of Dibutyryl Cyclic AMP, Glucagon, Insulin, and Triamcinolone
Authors: Schwartz Alan L , Rall Theodore W 
Published: September 2013

Incorporation of alanine-U-14C into glucose and liver glycogen increased linearly over sixty-five hours in culture of human fetal liver explants. This rate of incorporation was stimulated two- to tenfold by incubation with N6,2′O-dibutyry I adenosine 3′-5′:cyclic monophosphate (dibutyryl cyclic AMP) (0.1 mM) plus theophylline (0.5 mM) or glucagon (7.5 μg./ml.) plus theophylline. No apparent lag period was detected, and the hormonal effect continued throughout the observation period. Insulin (1 U./ml.) significantly decreased both the basal rate of incorporation and the stimulated rate resulting from dibutyryl cyclic AMP or glucagon incubation. These effects were observed at both high (10 mM) and low (2.8 mM) media glucose and from both 2.3 μM and 5 mM alanine-U-14C. Triamcinolone (20 μg./ml.) alone stimulated the rate of alanine-U-14C incorporation into glucose, whereas triamcinolone in the presence of dibutyryl cyclic AMP produced an increase in incorporation greater than the sum of the individual effects.
The basal incorporation of alanine-U-14C into glucose by these human fetal liver explants provide a rate of approximately 4 nmoles glucose/gm. min, which is discussed in relation to the physiologic needs of the fetus and newborn.
Plasma Lipid Levels in Diabetic Children: Effect of Diet Restricted in Cholesterol and Saturated Fats
Authors: Kaufmann R L , Assal J Ph , Soeldner J S , Wilmshurst E G , Lemaire J R , Gleason R E , White P 
Published: September 2013

Plasma lipids, blood glucose, and urinary glucose excretion were measured in 270 juvenile diabetic children upon admission to and throughout periods of summer camping during which the effect of a usual and a modified diabetic diet was assessed. The usual diabetic diet contained 700-1,500 mg. cholesterol daily with a polyunsaturated/saturated (P/S) ratio of 0.1, while the modified diet limited cholesterol to 300 mg. daily with a P/S ratio of 1.0. Both diets maintained calories with 40 per cent as fat, 40 per cent as carbohydrate, and 20 per cent as protein. Analysis of fasting blood glucose, qualitative and quantitative glucose excretion, and body weight indicated that groups were comparable except for the diet used.
Elevated mean levels of cholesterol and triglycerides were approximately equally distributed in diabetic children of both sexes upon admission to camp, with 24 per cent demonstrating hyperlipoproteinemia. Eleven per cent had type II, 10 per cent type IV, and 3 per cent type V hyperlipoproteinemia upon admission. After following the usual diet, 21 per cent were type II, 1 per cent type IV, and none type V, with no reduction in the over-all incidence of hyperlipoproteinemia despite lower triglyceride and glucose levels. After consumption of the modified diet, hyperlipoproteinemia was reduced to 5 per cent, with 4 per cent type II and 1 per cent type IV.
Results of this study indicated that plasma lipids in juvenile diabetics were elevated when first observed and that the control of blood sugar levels along with a diabetic diet with lower cholesterol and increased polyunsaturated fat significantly reduced the incidence of hyperlipoproteinemia more effectively than control of blood sugar levels alone.
Discordance of Diabetic Microangiopathy in Identical Twins
Authors: Karam J H , Rosenthal M , O'Donnell J J , Tsalikian E , Lorenzi M , Gerich J E , Siperstein M D , Forsham P H 
Published: September 2013

In a pair of 19-year-old monozygotic twin girls, one developed insulin-dependent, ketosis-prone diabetes at the age of three and has required insulin for the past 16 years. Her identical twin has maintained normal oral and intravenous glucose tolerance with normal insulin release and glucagon suppression. An unequivocal hypertrophy of the muscle capillary basement membrane(1,800 ± 148 Å) was found in the diabetic twin, while a normal thickness of 1,149 ± 62 Å was present in her nondiabetic sister. Follow-up of the present subjects and data from other discordant identical twins who have reached adulthood could determine whether muscle capillary basement membrane hypertrophy is an independent marker of genetic diabetes in adults.
Discordance of diabetic microangiopathy in a pair of monozygotic twins has important implications regarding the influence of heredity and environment on diabetic microangiopathy.
Effect of Insulin on the Exaggerated Glucagon Response to Arginine Stimulation in Diabetes Mellitus
Authors: Raskin Philip , Aydin Ismet , Unger Roger H 
Published: September 2013

The effect of insulin on the glucagon response to intravenous arginine was studied in eight juvenile-type and six adult-onset diabetics. In the juvenile-type diabetics, concomitant administration of insulin significantly blunted the glucagon response from a mean maximal rise of 310 ± 54 pg./ml. to only 184 ± 39 pg./ml. (p &lt; 0.01), about the same as in nondiabetics. In the adult-onset patients, however, insulin had no effect, the mean maximal rise being 250 ± 50 pg./ml. without insulin and 307 ± 71 pg./ml. with insulin (N.S.).
This study demonstrates that in juvenile-type diabetics concomitant administration of supraphysiologic quantities of insulin can reduce the exaggerated glucagon response to intravenous arginine to normal, whereas in the adult-type group, it has no apparent effect.
Glucagon Secretion from the Perfused Pancreas of Streptozotocin-treated Rats
Authors: Weir Gordon C , Knowlton Stephen D , Atkins Robert F , McKennan Kevin X , Martin Donald B 
Published: September 2013

One hour following intravenous streptozotocin, rat pancreases were perfused in situ, and , in contrast to saline-injected controls a marked decrease of insulin secretion was observed. In these streptozotocin-treated animals, baseline glucagon secretion was enhanced when the perfusate glucose concentration was either 80 mg./100 ml. or 300 mg./100 ml. In addition there was hypersecretion of glucagon in response to arginine.
Exogenous insulin (20,000 μU./ml.) could suppress glucagon secretion when endogenous secretion was plentiful. Baseline and arginine-stimulated glucagon secretion of the streptozotocin treated animals was not suppressed by large amounts of glucose and insulin to the degree seen in control animals. The glucagon rise in response to an abrupt fall of glucose from 80 mg./100 ml. to 25 mg./100 ml. was not significantly higher in the control group than in the streptozotocin group.
The results seen with epinephrine were in sharp contrast to those found with arginine. Epinephrine-stimulated glucagon secretion was not enhanced in the streptozotocin group. In addition, epinephrine-induced secretion could be suppressed by exogenous insulin in both the control and streptozotocin groups. The differences may be secondary to differences of endogenous insulin secretion.
The present results are compatible with the hypothesis that local insulin secretion can exert a significant suppressive effect upon the alpha cell and that the inhibition of glucagon secretion by glucose is partially mediated by this mechanism. Furthermore, anomalous local insulin secretion may contribute to the abnormal glucagon secretion of diabetes mellitus.
Differential Sensitivity of Glycogenolysis and Gluconeogenesis to Insulin Infusions in Dogs
Authors: Chiasson J L , Liljenquist J E , Finger F E , Lacy W W 
Published: September 2013

The suppressive effect of insulin on hepatic glucose production is generally recognized. Though it is well established that this effect is at least partially due to inhibition of glycogenolysis, controversy still exists about insulin's effect on gluconeogenesis. The present study was undertaken to determine whether insulin could affect gluconeogenesis from alanine in the intact dog and to compare the effect of insulin on glycogenolysis and gluconeogenesis.
In anesthetized dogs fasted overnight, blood samples were drawn simultaneously from a femoral artery and hepatic vein. Alanine-U-14C, 10 μCi./kg., was infused over 110 minutes. A constant insulin infusion at either 1 or 5 mU./kg./min. was begun at 50 minutes, and blood glucose concentration was maintained by a variable glucose infusion. When insulin was infused at 1 mU./kg./min., resulting in plasma immunoreactive insulin (IRI) levels of 73 ± 10 μU./ml., the net splanchnic glucose production (NSGP) was suppressed from 2.7 ± 2 mg./kg./min. to virtually zero. In constrast, this small increment in insulin concentration had no demonstrable effect on the net splanchnic uptake of alanine or on the conversion of plasma alanine to glucose (7.9 ± 0.3 μmol/min.). Insulin infused at 5 mU./kg./min. resulted in IRI levels of 240 ± 25 muU./ml. This higher insulin concentration was associated with a marked suppression of both the NSGP (100 per cent) and the conversion of plasma alanine to glucose (90 per cent) but did not affect the extraction of alanine by the splanchnic bed. Doses of both 1 and 5 mU./kg./min. were associated with a 35 per cent fall in immunoreactive glucagon levels.
These data demonstrate that (1) glycogenolysis is more sensitive than gluconeogenesis to the inhibitory effect of small increments in insulin concentrations, (2) gluconeogenesis could be suppressed by insulin but only at higher insulin concentrations, (3) this suppression of gluconeogenesis from alanine by insulin was due to an intrahepatic effect rather than an effect on the splanchnic extraction of alanine, and finally, (4) that insulin can suppress glucagon in the absence of hyperglycemia.