bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of Fatty Acid Metabolism by Glucagon in Man: I. Effects in Normal Subjects
Authors: Schaded David S , Philip Eaton R 
Published: September 2013

This investigation was designed to examine the contribution of glucagon to the regulation of free fatty acid (FFA) metabolism in man. The acute effects of exogenous glucagon upon the concentration of plasma FFA and its metabolities: acetoacetic acid (AcAc), beta hydroxybutyric acid (BOH), and triglyceride (TG) were assessed in five normal male subjects. The threshold of response was determined by administering intravenous glucagon in a graded dose-response fashion, and assessing the magnitude of change in FFA and its metabolities.
A prompt rise in FFA concentration occurred after glucagon injection, and was associated with a synchronous elevation in both Ac Ac and BOH concentration in the plasma. The rise in FFA concentration was maximal with the glucagon dosage of 0.5 μg./kg. with no greater FFA response seen at higher hormone dosage. In contrast, the rise in plasma ketones was linearly related to the dosage of glucagon but not to the corresponding rise in FFA concentration. The behavior of plasma triglyceride concentration following glucagon challenge also contrasted with the linear rise in ketone concentration. At the lowest dosage of glucagon, TG concentration rose transiently, while at the highest two dosages the concentration of TG was reduced. The transitional dosage of hormone at which no change in TG concentration was observed was approximately 0.5 μg./kg. Comparing our in vivo data with the conclusions reached from published liver perfusion studies, it can be suggested that in the dosages employed, glucagon acutely elevates plasma FFA concentration and modulates their metabolism by augmenting conversion to AcAc and BOH while tending to reduce conversion to TG in man.
Modulation of Fatty Acid Metabolism by Glucagon in Man: II. Effects in Insulin-deficient Diabetics
Authors: Schade David S , Philip Eaton R 
Published: September 2013

The potential role of glucagon in the pathogenesis of diabetic ketogenesis was examined by intravenous glucagon administration (1.0 μg/kg. body weight) in five insulin-deficient diabetic subjects. The metabolic response was defined by examining the changes in the plasma concentration of insulin, glucose, free fatty acids (FFA), triglycerides, betahydroxybutyrate, and acetoacetate in comparison to those changes occurring in five nondiabetic control subjects tested under identical experimental conditions.
Our results demonstrate that in the absence of endogenous insulin secretion, exogenous glucagon administration results in an enhanced ketonemia independent of the rise of FFA substrate. This augmented ketogenic response to glucagon in diabetic subjects was not reflected in the dynamics of glucose regulation, with similar changes in blood glucose concentration occurring in both diabetic and nondiabetic populations.
These data demonstrate that glucagon may potentiate ketonemia in insulin-deficient diabetics, although the mechanism mediating this augmentation is not defined. Since the rise in FFA substrate was indistinguishable in the diabetic as compared to the control group, increased hepatic conversion of FFA substrate into ketone bodies is suggested.
Antigenicity of “Monocomponent” Pork Insulin in Diabetic Subjects
Authors: Yue D K , Turtle J R 
Published: September 2013

“Single-peak,” “single-component,” and “monocomponent” insulins have been produced in an attempt to eliminate insulin antigenicity. Recently “single-peak insulin” has been shown to be antigenic. From animal experiments and preliminary human studies it has been claimed that monocomponent (MC) insulin is nonantigenic or only negligibly so. In this study the antigenicity of MC insulin was determined in two groups of diabetic patients. In group 1, seven patients treated with insulin for the first time were given MC insulin for seven to fifteen months. Four of the seven patients developed significant IgG insulin antibodies after four to ten months. In one patient the IgG insulin antibody concentration was high (8.51 mU./ml.). In two patients IgG proinsulin-specific antibodies were detected. In group 2, fourteen patients with unstable diabetes, insulin allergy, or resistance were changed from conventional to MC insulin. Treatment with MC insulin did not decrease insulin requirement or improve diabetic control when assayed by the M factor. After seven to eleven months of therapy there was no significant fall in insulin antibodies except in two patients in whom corticosteroids had been administered simultaneously.
These results differ significantly from those previously reported and could be interpreted as suggesting that insulin itself is antigenic. When the purity of the MC insulin was determined, significant contaminants could be demonstrated in all of ten separate batches of MC insulin. Gel chromatography, polyacrylamide gel electrophoresis, and proinsulin radioimmunoassay were used to identify the presence of nonconvertible insulin dimer, proinsulin, and monodesamido insulin in antigenically significant concentrations.
The generation of IgG insulin antibodies in MC-insulin-treated patients cannot be interpreted as a true indication that insulin itself is antigenic. The problem of insulin antigenicity has not been resolved and will not be until a highly purified insulin is available. Unfortunately, the MC insulins do not meet these requirements.
Renal Substrate Exchange in Human Diabetes Mellitus
Authors: Wahren John , Felig Philip 
Published: September 2013

Renal substrate exchange was examined in five male patients with insulin-dependent diabetes mellitus of several years' duration. Insulin was withheld for twenty-four hours prior to the study. A renal vein was catheterized from the femoral vein, and PAHclearance was employed for the determination of effective renal blood flow.
None of the patients was in ketoacidosis, but all were moderately hyperglycemic in the fasting state (16.8±1.5 mmol/L.) (225-384 mg./100 ml.). Nevertheless, no net release of glucose from the kidney was detectable. Instead, there was a significant net renal uptake of glucose (320±80 μmol/min.). In addition, there was a significant net uptake of glycerol and a net release of pyruvate. Renal amino acid exchange was similar to that reported for healthy subjects: glutamine, glycine, proline, and citrulline were taken up and serine, alanine, cystine, tyrosine, and threonine were released by the kidney.
It is concluded that (a) in nonketoacidotic diabetics there is no net production of glucose by the kidney; (b) renal amino acid exchange in diabetics is similar to that of healthy individuals; and (c) the kidney is not an important gluconeogenic organ in human diabetes.
Glucagon Response to Arginine after Treatment of Diabetes Mellitus
Authors: Ohneda Akira , Ishii Shoji , Horigome Ken , Yamagata Shoichi 
Published: September 2013

To investigate the aminogenic glucagon response in diabetes mellitus, arginine infusion tests were carried out on twenty-four diabetic patients before and after treatment. Eleven healthy men served as a control group. Plasma glucagon was measured by radioimmunoassay using an antiserum, G21, specific for pancreatic glucagon. Out of twenty-four patients, five were treated with diet alone, eight with sulfonylurea, and eleven with insulin.
In all these diabetic groups, the glucose tolerance improved after treatment for diabetes mellitus, while the insulin response to the glucose did not show any remarkable change. The fasting levels of the plasma glucagon did not differ from that of the normal subjects both before and after treatment. Hyperresponsfveness of the plasma glucagon to arginine infusion was observed in all diabetic groups, in comparison with that of the normal controls. The exaggerated response of the plasma glucagon to arginine was lowered following appropriate treatment in each diabetic group. However, as far as the changes in glucagon area during the arginine test are concerned, the aminogenic hyperresponsiveness of the plasma glucagon was reduced prominently in the diabetic group treated with sulfonylurea. The relationship between the response of glucose and plasma insulin and between glucose and glucagon to arginine was investigated, and the importance of the changes in the insulin:glucagon ratio was emphasized. Moreover, the possibility that long-term administration of a sulfonylurea may reduce an exaggerated glucagon response to arginine was discussed.
Age-adjusted Analysis of Insulin Responses During Normal and Abnormal Glucose Tolerance Tests in Children and Adolescents
Authors: Rosenbloom Arlan L , Wheeler Lawrence , Bianchi Raymond , Chin Frank T , Tiwary Chandra M , Grgic Ante 
Published: September 2013

This report analyzes age-specific glucose (PG) and immunoassayable insulin (IRI) responses during oral glucose tolerance testing (OGTT) and examines test results in children and adolescents with OGTT abnormality using the age-appropriate control data. Controls' (n = 93) and patients' (n = 63) results were compared on the basis of statural age (SA) at the time of testing. Control tests (n = 101) showed significant positive correlation of fasting and fourhour postingestion PG with SA (p &lt;0.001), but mean area under the PG curves did not vary between the SA groups (I—18-69 months, 11—70-131 months, III—132+ months). The absence of differences at other sampling times permits uniform diagnostic criteria for this age group. IRI was positively correlated with SA at aU testing times, and mean levels differed significantly between each SA group at every sampling time; the mean areas under the IRI curve also differed significantly between SA groups as did the mean ratios of IRI area to PG area (group I—0.2639 ± 0.0175 S.E.M., groupII—0.3864 ± 0.0235, group III—0.6262 ± 0.0491).
Patient tests (n = 110) were separated into normal (N), borderline (B), and chemical-diabetic (C) for each SA group. IRI means were above control data for each test type in each SA group at all sampling times; one fourth of these differences were significant. IRI responses also increased within each SA group from N to B to C tests. Mean IRI areas and IRI area to PG area mean ratios were higher than in controls, and this difference was greatest with the most abnormal (C) test type in each SA group.
A subgroup of three patients who had low IRI responses from the outset and developed overt diabetes in one to three years was excluded from the analysis. In contrast to apparent relative insulin inefficiency with normal maturation and with chemical diabetes, they had exceptional responsiveness to their low IRI levels. Variable involvement of alpha as well as beta cells in the pathophysiology of diabetes is suggested as one explanation for these paradoxic observations. Changing receptor affinity might also be implicated.
Relationship of Serum Glucose Concentration to Changes in Refraction
Authors: Gwinup Grant , Villarreal Arnold 
Published: September 2013

The effect of chronic changes in serum glucose concentration on refraction was studied by increasing the dose of insulin or chlorpropamide in 10 diabetic patients who initially had relatively high glucose concentrations. In every case when serum glucose concentration was reduced the vision became less myopic or more hyperopic.
To assess acute changes, 10 diabetics (including four with aphakic eyes) were given an intravenous injection of glucose. In patients with intact lenses the vision became more myopic or less hyperopic following the administration of glucose, but in the aphakic eyes hyperopia increased.
It is concluded from both the acute and chronic studies that higher levels of serum glucose concentration produce myopia and lower levels produce hyperopia. Furthermore, these changes are related to changes in the optical properties of the crystalline lens.
A Nonsuppressible Increase of Glucagon Secretion by Isolated Islets of High-protein-fed Rats
Authors: Eisenstein Albert B 
Published: September 2013

We recently demonstrated increased plasma glucagon but normal insulin in rats fed a high-protein, carbohydrate-free (HP) diet; however, other investigators have reported that both plasma glucagon and insulin are increased after protein feeding. For this reason, we have investigated the effects of an HP diet on pancreatic secretion of insulin and glucagon. Male rats were fed an HP or control diet for one, three, or five days, and, at the end of the feeding period, blood was taken for glucose, insulin, and glucagon determinations. Additional animals fed the HP and control diets for up to. 10 days were sacrificed, the pancreases removed, and islets of Langerhans isolated. Islets were incubated for 30 minutes in media with glucose concentration of 1.7, 8.3, 16.7, or 33.4 mM. Insulin and glucagon secreted into the media were determined by radioimmunoassay.
Plasma insulin was markedly reduced after one day of HP feeding but gradually returned to normal by the fifth day. Plasma glucagon was not altered on day 1 but was significantly increased after three days of HP feeding. The I/G molar ratio, which declined precipitously on day 1, increased thereafter but, as shown previously, remained at a level that promotes gluconeogenesis for up to 10 days.
Insulin secretion by isolated islets of control and HP rats increased more than 10-fold as medium glucose was raised from 1.7 to 16.7 mM. There was no difference in insulin release by the two groups of islets. Glucagon secretion by HP islets at low medium glucose remained normal during the first five days; however, beginning on day 3 there was gradual loss of the suppressive effect of high medium glucose on glucagon secretion. After one week of HP feeding, glucagon secretion at low medium glucose was doubled and there was complete lack of suppression of the elevated hormone production by high medium glucose. The alterations of alpha-cell function induced by HP feeding are similar to those found in human and experimental diabetes.
Effects of Acute Insulin Withdrawal and Administration on Plasma Glucagon Responses to Intravenous Arginine in Insulin-dependent Diabetic Subjects
Authors: Gerich John E , Lorenzi Mara , Tsalikian Eva , Bohannon Nancy V , Schneider Victor , Karam John H , Forsham Peter H 
Published: September 2013

To assess further the role of insulin in the abnormal alpha-cell dysfunction found in human diabetes mellitus, the effects of acute insulin withdrawal and administration on plasma glucagon responses to intravenous arginine were studied in eight insulin-dependent diabetic subjects. Arginine infusions (30 gm. over 30 minutes) were performed during and at one and four hours after discontinuation of a 14-hour insulin infusion (1.5 U. per hour), which had rendered the subjects euglycemic, and on another occasion before and one and four hours into a five-hour infusion of insulin (1.5 U. per hour). During the last hour of the 14-hour infusion, glucagon responses to arginine (area under the curve, nanograms per milliliter per minute) were similar to those found in normal subjects (10.3 ± 0.8 vs. 9.0 ± 0.8, respectively). After discontinuation of the insulin infusions, glucagon responses increased progressively (p &lt; 0.01) to values (16.8 ± 1.2) that exceeded those of normal subjects by four hours (p &lt; 0.01). These were similar to results found in the same subjects studied when their diabetes was in &lt; optimal control (14.9 ± 1.3). Infusion of insulin under these conditions progressively decreased glucagon responses to arginine to values (9.6 ± 0.8; p &lt; 0.01) that, at four hours, were similar to those of normal subjects and to values found at the end of the 14-hour infusion of insulin in the same diabetic individuals.
These results demonstrate a rapid effect of insulin on glucagon responses to arginine and suggest that the abnormal responses seen in diabetes mellitus are the immediate result of insulin deficiency. Since abnormal glucagon responses to glucose in diabetes are not as readily corrected by insulin, the mechanisms underlying the abnormal responses to these two stimuli may differ.
Effect of Environmental Temperature on Glucose-induced Insulin Response in the Newborn Rat
Authors: Kervran Alain , Gilbert Marc , Girard Jean R , Assan Roger , Jost Alfred 
Published: September 2013

Blood glucose and plasma insulin and glucagon concentrations were determined in full-term rats delivered by cesarean section and exposed to 37° C. or 24° C. environmental temperature during the first hours of extrauterine life.
When newborn rats were maintained at thermal neutrality (37° C.), a transient period of hypoglycemia of two hours occurred, associated with a rapid fall in plasma insulin and a rise in plasma glucagon concentrations. During cold exposure (24° C.), the blood glucose level remained stable over the four hours studied; the decrease of plasma insulin was sluggish while the rise of plasma glucagon was unchanged.
In newborn rats maintained at 37° C., an intraperitoneal glucose load one hour after delivery produced a marked rise in blood glucose and plasma insulin concentrations one hour later. The distribution of experimental points suggested a sigmoidal dose-response curve. By contrast in newborn rats kept at room temperature (24° C.) the same glucose load did not induce any increase in plasma insulin in spite of hyperglycemia. However, phentolamine resulted in pronounced plasma insulin rise in hypothermic newborns in response to glucose administration. From these observations it is concluded that the in-vivo unresponsiveness of the beta cells to glucose at birth, reported by others, is mainly due to the experimental conditions.
Growth Hormone Levels in Diabetes: Correlation with the Clinical Control of the Disease
Authors: Vigneri R , Squatrito S , Pezzino V , Filetti S , Branca S , Polosa P 
Published: September 2013

We carried out contemporaneous daytime blood sugar and growth hormone (HGH) determinations in eight juvenile and six middle-aged diabetics under both poor and good metabolic control. A continuous blood sampling technic was used. The following results were obtained:
1. HGH values in poorly controlled diabetics were higher and more fluctuating than in normals of a corresponding age.
2. After good control was reached, a significant HGH decrease was observed in all patients but one. In this condition HGH levels were normalized in middle-aged diabetics but not in juvenile ones. In the latter group HGH values, even if decreased, were persistently higher than in controls of the same age.
3. No difference was observed between newly diagnosed diabetics and patients known to have had diabetes for some years.
Our data support the suggestion that HGH abnormalities in diabetes are a consequence of the metabolic disturbance.
Insulin and Free Fatty Acid Levels During Oral Glucose Tolerance Tests and Their Relation to Age in 70 Healthy Children
Authors: Lestradet H , Deschamps I , Giron B 
Published: September 2013

In 70 healthy children aged from three months to 15 years, blood glucose, immunoreactive insulin, and free fatty acids were measured during a three-hour glucose tolerance test. The results are presented for the whole group as well as for three age groups: three months-five years, six-10 years, and 11–15 years.
It is demonstrated that (1) glucose levels are significantly lower in young children (younger than five years); (2) there are no significant age-related changes in free fatty acid concentration; (3) insulin levels are increasing constantly and significantly with age, the most strikingly at the age of onset of puberty; the absence of notable changes in glucose tolerance results in a rise of the I/G ratio as well.
The causes for the increase of insulin secretion with age, whether of peripheral or pancreatic order, are still speculative.
Inhibition of Lymphocyte Blastogenesis by Factor(s) in Alloxan-diabetic Rat Plasma
Authors: Pallavicini Maria G , Nichols William K 
Published: September 2013

Supplementation of rat lymphocyte cultures with plasma from alloxan-diabetic rats produced a dose-dependent suppression of mitogen-induced blastogenic responses. Viability measurements indicated that this inhibition was not due to a direct cytotoxic effect of alloxan-diabetic plasma on rat mononuclear leukocytes in vitro. This inhibition was not explained by hyperglycemia alone and was observed when blastogenesis was induced in vitro by phytohemagglutinin (PHA), concanavalin A (con A), or allogeneic cells. Peripheral blood lymphocytes from alloxan-diabetic rats appeared to be more sensitive than normal cells to the inhibitory effect of diabetic plasma.
Heating at 56° for 60 minutes produced only a partial loss of the inhibition by diabetic plasma. Alloxan-diabetic rat plasma promoted an increased accumulation of adenosine 3′,5′-monophosphate (cyclic AMP) in mononuclear leukocytes. Insulin (1 and 100 μU./ml.) in vitro enhanced PHA-induced blastogenesis but failed to reverse the inhibition caused by diabetic plasma. Ultrafiltration through a cellulose dialysis membrane with an exclusion size of 12,000 molecular weight did not remove the inhibitory factor(s).
These results indicate that a depressed cellular immune response is produced during an insulin-deficient diabetic state. The suppressed in-vitro blastogenic response of lymphocytes from alloxan-diabetic rats appears to involve some circulating inhibitory factor(s) in diabetic plasma. This inhibition may be explained, in part, by the ability of diabetic plasma to elevate cyclic AMP in mononuclear leukocytes.
Immunopathology of Renal Extracellular Membranes in Diabetes Mellitus: Specificity of Tubular Basement-membrane Immunofluorescence
Authors: Miller Kenneth , Michael Alfred F 
Published: September 2013

This study documents the presence of marked immunofluorescence for IgG and albumin in renal extracellular membranes, especially tubular basement membranes (TBM), of patients with severe diabetic nephropathy. A comprehensive immunofluorescent analysis was carried out on kidney tissue from 83 patients—Group I: 24 living normal renal allograft donors and two infants less than one week of age. Group II: 24 patients with severe nephropathy who had juvenile onset of diabetes 16 to 30 years previously and who ranged in age from 20 to 47 years. Group III: 33 patients with severe kidney disease of varied etiologies with an age range of five to 63 years. The sections were assayed for a variety of proteins (immunoglobulins, complement components, and tissue antigens). Kidney sections of all patients with severe diabetic nephropathy were readily distinguished from kidneys of other patients and normals by the intense linear staining of the extracellular membranes, especially the tubular basement membrane, for IgG and albumin. Dual-labeled studies using FITC anti-basement-membrane (BM) and tetramethyl rhodamine (TMR) antialbumin demonstrated localization of the albumin predominantly to the outer but also the inner TBM while the BM antisera reacted more intensely with the inner membrane. There is no evidence that an immunologic process is responsible for these Findings.
These immunofluorescent findings are specific for severe diabetic nephropathy and may reflect structural changes in the renal extracellular membranes that permit entrapment of serum proteins, possibly due to changes in permeability.