bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Pathogenic Role of an Insulin-receptor Defect in Diabetes Mellitus of the Obese
Authors: Beck-Nielsen Henning 
Published: September 2013

I-125-insulin binding to circulating monocytes was measured in 12 obese, maturity-onset diabetic patients, in 10 obese subjects, and in 12 normal persons. The diabetic obese patients were extremely insulin resistant and had an impaired glucose tolerance, while the normoglycemic obese subjects were slightly insulin resistant and had borderline values of glucose tolerance. The insulin secretion pattern of diabetic obese patients after a glucose load differed from that of the normal and normoglycemic obese subjects, showing a low initial response.
Insulin binding to monocytes from diabetic obese patients showed a 40 per cent decrease when compared with normal persons (p &lt;0.05). Furthermore, insulin binding to monocytes was about 20 per cent lower in diabetic obese than in normoglycemic obese subjects. However, this difference was not statistically significant (p &gt;0.1). In the total group of persons studied, the insulin binding correlated positively to both glucose tolerance (R = 0.69, p &lt;0.001) and insulin sensitivity (R = 0.74, p &lt;0.001). In the separate groups we also found a statistically significant correlation between insulin binding and insulin sensitivity in normoglycemic obese (R = 0.69, p &lt;0.05) but not in diabetic obese subjects (R = 0.36, p &gt; 0.1)
After 10 days of treatment with a 1200-kcal. diet the diabetic patients exhibited significant increases in glucose tolerance (p &lt; 0.01), in insulin sensitivity (p &lt; 0.01), and in insulin binding (p &lt; 0.01)
We conclude that a close correlation exists between insulin binding and insulin sensitivity in the three groups studied. Among obese subjects the correlation was less pronounced (statistically insignificant) in diabetic obese persons, emphasizing that, especially in this group, there are other factors of importance for the insulin resistance in addition to the receptor defect.
Carbohydrate Diet-induced Changes in Very Low Density Lipoprotein Composition and Structure
Authors: Witztum Joseph L , Schonfeld Gustav 
Published: September 2013

High carbohydrate (CHO) diets cause accumulation in plasma of larger, triglyceride (TG)-enriched very low density lipoprotein (VLDL) particles. In man, the composition of the VLDL is changed by such diets as well. The source of the altered VLDL particles is presumed to be the liver, but the intestine is known to secrete VLDL, and VLDL is also altered during its postsecretory catabolism. To ascertain that the liver is a source of “diet-induced VLDL,” we fed rats CHO and control diets and we examined plasma levels of lipids chemically and apoproteins A-I (ApoA-I) and B (ApoB) by specific radioimmunoassay (RIA). VLDL (d &lt; 1.006) and VLDL density subfractions were isolated and their composition studied by RIA, column chromatography, isoelectric focusing (IEF), and polyacrylamide gel electrophoresis. Livers from control and CHO-fed rats were perfused in vitro. Whole perfusates and perfusate VLDL were studied similarly.
In the CHO-fed rats, plasma TG increased, cholesterol and ApoA-I remained unchanged, and ApoB fell. The VLDL isolated were TG enriched and less dense. Although total VLDL-protein rose, the proportion of VLDL-protein that was ApoB and arginine-rich protein (ARP) fell, while ApoC rose. The ApoB content varied directly with density of particles. ARP subunits were not changed, but relative proportions of ApoC-III0 rose from 39 to 46 per cent of dye uptake on IEF gels and ApoC-III3 fell from 34 to 26 per cent. Thus, CHO feeding produced altered plasma VLDL in the rat.
The perfused livers of the CHO-fed rat secreted more TG, but absolute secretory rates for cholesterol, ApoB, and ApoA-I were unchanged. The VLDL isolated from perfusates were larger, TG-enriched, and less dense. Although VLDL-protein rose, the proportion that was ApoB fell; both ApoC and ARP rose, ARP sub-units were unchanged, while ApoC-III0 rose from 29 to 37 per cent and ApoC-III3 fell from 48 to 42 per cent. In contrast to plasma, ApoC content was not increased relative to ARP. As in plasma, content of ApoB varied with particle density.
Thus, CHO feeding induced changes in hepatic perfusate VLDL structure and composition that in general paralleled those changes seen in plasma. This strongly suggests that the action of diet on the liver is responsible for many of the changes seen in plasma VLDL. On the other hand, the discrepancy between the VLDL-ApoC content and subunit proportions of plasma and perfusate suggests that the discrepancy is due to postsecretory processing. Similarly, the failure to see decreases in absolute hepatic ApoB secretion, while plasma ApoB levels fell, suggests that the postsecretory metabolism of ApoB-containing lipoproteins is also altered by diet. In addition, the failure to see increases in hepatic VLDL-ApoB secretory rates at a time when VLDL-TG and VLDL-protein increased suggests that there is no tight coupling between the secretion of ApoB and lipids.
24-Hour Studies of the Effects of Somatostatin on the Levels of Plasma Growth Hormone, Glucagon, and Glucose in Normal Subjects and Juvenile Diabetics
Authors: Christensen S E , Hansen Aa P , Weeke J , Lundbaek K 
Published: September 2013

Somatostatin was infused in various doses into normal subjects and juvenile diabetics for a 24-hour period preceded by a 24-hour control period and followed by another three-hour control period. Saline was infused during the first control period. Meals were served during the two 24-hour periods. Blood samples were taken hourly.
Five normal males received a total dose of 4 mg. somatostatin. Four male diabetics received 2 mg., four received 4 mg., and four 6 mg. In the diabetics, somatostatin suppressed plasma growth hormone, glucagon, and glucose throughout the infusion. All parameters rebounded at cessation of infusion. In the normals, somatostatin suppressed plasma growth hormone, glucagon, and insulin but increased plasma glucose.
It is concluded that the plasma glucose suppression in the diabetics is mainly due to the suppression of the diabetogenk hormones growth hormone and glucagon. A minor effect of decreased and/or delayed absorption of carbohydrates cannot be excluded in these experiments. The elevated plasma glucose levels in normals must be due to the suppressive effects of somatostatin on insulin secretion.
Effect of Glucose on the Glucagon Response to L-dopa in Normal and Diabetic Subjects
Authors: Klimeš Iwar , Vigaš Milan , Jurčovičová Jana , Repčeková Daniela , Kolesár Pavel 
Published: September 2013

The effect of an oral dose of 1 gm. L-dopa either without or after a concomitant oral administration of 100 gm. glucose on the plasma level of pancreatic glucagon, plasma immunoreactive insulin (IRI), and plasma growth hormone (GH) was assessed in eight normal and 10 insulin-treated diabetic subjects. In the normal group the stimulatory effect of L-dopa on pancreatic glucagon release was reconfirmed. Moreover, in the diabetics essentially the same plasma glucagon increase after drug administration was found, such a response being inhibited in both groups by glucose.
The increase of plasma GH after L-dopa in both healthy persons and diabetics and the inhibition of this response by glucose in healthy subjects was reconfirmed. Furthermore, the same effect of exogenous glucose on the L-dopa-induced GH release was observed in diabetics.
It may be concluded that glucagon may play a pathogenetic role in the worsening of parkinsonian diabetic patients during the treatment with L-dopa and that diabetic hyperglycemie per se seems to be insufficient for an inhibition of the release of both glucagon and GH after L-dopa.
Effect of Insulin Therapy on the Profiles of Plasma Immunoreactive Glucagon in Juvenile-type and Adult-type Diabetics
Authors: Raskin Philip , Unger Roger H 
Published: September 2013

To determine if the abnormal A-cell function of human diabetes can be corrected by insulin therapy, 10 patients with juvenile-type and 10 with adult-onset types of diabetes were aggressively treated with insulin for up to 10 days. Glucose, immunoreactive glucagon (IRG), and, where possible, insulin were measured in plasma specimens obtained at two-hour intervals for periods of up to 10 days. These patients were compared with nine nondiabetics who were studied similarly.
During a two-day “uncontrolled” period, marked hyperglycemie, glycosurie, and elevated IRG concentrations were present in both groups of diabetic patients. “Improved control” was achieved in the juvenile-type diabetic group with an average insulin dose of 115 ± 24 U. per day. Such therapy significantly reduced the mean plasma glucose (p &lt; 0.001) and IRG (p &lt; 0.05) concentrations when compared with the “uncontrolled” period, but both remained above (p &lt; 0.05) the values seen in the nondiabetk subjects.
“Improved control” was achieved in the maturity-onset group of patients with an average insulin dose of 160 ± 24 U. per day. This dose was associated with a mean plasma-insulin value of 106 ± 26 μU. per milliliter, significantly greater (p &lt; 0.05) than that of the nondiabetk: group. Mean plasma glucose (p &lt; 0.001) and IRG (p &lt; 0.02) concentrations were reduced significantly as compared with the “uncontrolled” period; the mean IRG level was the same as that of the nondiabetics, but the mean plasma glucose levels remained significantly greater (p &lt; 0.001) than in the nondiabetics.
The results indicate that aggressive administration of insulin by conventional means does significantly reduce the average IRG level in juvenile-type and adult-type diabetics. However, despite the large doses of insulin and unphysiologically high concentrations of circulating insulin in the juvenile-diabetic group, IRG remained significantly above that of the nondiabetics. In the adult-onset group, although it was reduced to normal, the IRG level can be viewed as above normal relative to the persistent hyperglycemie and hyperinsulinemia.
Glucose Tolerance in Viral Hepatitis: A Study of Twenty Patients During the Acute Phase and After Recovery
Authors: Chupin Maurice , Charbonnel Bernard , Bodic Louis Le , Grolleau Jean-Yves , Chupin Françoise , Guillon Jean 
Published: September 2013

Twenty patients with viral hepatitis were investigated during the acute phase and after recovery in order to study their glucose tolerance. During hepatitis, three tests were performed: oral and intravenous glucose tolerance tests and tolbutamide test, with measurements of glucose, insulin, free fatty acids, trigiycerides, growth hormone, and cortisol. After recovery, a control oral glucose tolerance test was performed. All these results were compared with those of healthy controls.
During the acute phase, both oral and intravenous glucose tolerance tests showed two groups of patients: nine with normal glucose tolerance but significant hyperinsulinism, and 11 with glucose intolerance but a delayed and not increased insulin response. Tolbutamide test was always normal, without any difference between these two groups.
Free fatty acids (FFA) were increased only in the glucose-intolerant group; there was a significant negative correlation between basal FFA and the K values. Trigiycerides were increased in the two groups, but were higher in the normal glucose-tolerant one. Growth hormone and cortisol were increased only when the K value was very low.
All these parameters returned to normal in all the patients after their recovery.
Clinical features, hepatic tests, and HLA typing were similar in the two groups, with no significant differences. A comparative group of patients with mild and nonhepatic infections did not show any abnormalities.
This study suggests there is a transitory insulin-resistant state during viral hepatitis, which can be due to an increase in FFA concentrations. Glucose intolerance occurs in half of the cases, possibly as a consequence of an additional β-cell impairment.
Interactions of Obesity and Glucose-stimulated Insulin Secretion in Familial Hypertriglyceridemia
Authors: Maruhama Yoshisuke , Abe Ryuzo , Okuguchi Fuminobu , Oikawa Shinichi , Ohneda Akira , Goto Yoshio 
Published: September 2013

Plasma lipids and lipoproteins, glucose tolerance, plasma insulin response to glucose load, and liver function were examined in 81 relatives of 12 index cases with primary endogenous hypertriglyceridemia, hyperinsulinemia, and hepatic steatosis, as well as in 90 nonrelatives, including the spouses, as controls. Insulin hypersecretion (with or without glucose intolerance), endogenous hypertriglyceridemia, and abnormal liver function suggesting hepatic steatosis were shown to exist in the relatives mostly in combined fashion. Correlation analysis and stepwise multiple regression analysis revealed that the combined disorder developed on the basis of obesity. The incidence of diabetes mellitus was significantly high in the relatives (14.8 per cent) as compared with the normal Japanese population (3.5 per cent).
Although the vertical transmission of the combined disorder was noted in almost all pedigrees, the frequency distribution analysis of insulin response, glucose tolerance, and plasma triglyceride showed the histograms of these variables similarly skewed to the right as compared with those in the controls, with no apparent bimodality.
In view of the hitherto suggested role of insulin in triglyceride metabolism, it is concluded that hyperinsulinemia coupled with obesity seems to be the basic trait of this form of familial hypertriglyceridemia and hepatic steatosis, though the mode of transmission remains to be elucidated.
Diabetes Screening Using a Quantitative Urine Glucose Method
Authors: Davidson John K , Reuben David , Sternberg James C , Ryan William T 
Published: September 2013

Sensitivity and specificity of three methods (random urine glucose (RUG) &gt; 25 mg. per deciliter; positive Clinitest; and random plasma glucose (RPG) &gt; 140, &gt; 120, and &gt; 100 mg. per deciliter) for detecting the unknown diabetic were compared. In 1,952 screenees, RUG of 96.7 per cent was 3 to 25 mg. per deciliter (normoglucosuria), RUG of 2.0 per cent was 26 to 100 mg. per deciliter (moderate hyperglucosuria), and of 1.3 per cent was &gt; 100 mg. per deciliter (marked hyperglucosuria). Twenty-five randomly selected from each of the first two groups and 18 from the third group had a glucose tolerance test (GTT); seven in the third group had fasting plasma glucose tests &gt; 150 mg. per deciliter. GTTs were evaluated by United States Public Health Service (USPHS), Fajans-Conn (F-C), and summation (S) criteria, and tested screenees divided into nondiabetic (ND) and diabetic (DM). NDs with RUG &gt; 25 mg. per deciliter were false positive screens: renal hyperglucosurics (RHG) if GTT urine glucose ≥ 80 mg. per deciliter, nonrenal hyperglucosurics (NRHG) if GTT urine glucose ≤ 25 mg. per deciliter. The prevalence of DM was 1.24 per cent (USPHS), 1.37 per cent (F-C), and 1.45 per cent (S). The prevalence of false positives (USPHS) was 2.04 per cent (1.19 per cent RHG and 0.85 per cent NRHG). In the normoglucosuria group, 100 per cent who had a GTT were true negatives. In the moderate hyperglucosuria group, 16 per cent (USPHS) were true positives, 84 per cent false positives (44 per cent RHG, 40 per cent NRHG). In the marked hyperglucosuria group, 72 per cent (USPHS) were true positives, 28 per cent false positives (24 per cent RHG and 4 per cent NRHG). By Clinitest, 23 per cent of the DMs (USPHS) were false negatives, and 1.8 per cent in the normoglucosuria group were false positives. Nine per cent of the DMs were false negatives by RPG &gt; 140, and 4.5 per cent were false negatives by RPG &gt; 120.
RUG &gt; 25 mg. per deciliter was as sensitive as the GTT in detecting unknown DMs but was less specific. Random normoglucosuric screenees are unlikely to have diabetes; about 40 per cent of random hyperglucosuric screenees have diabetes.
Somatostatin and Pancreatic Polypeptide Secretion: Effects of Glucagon, Insulin, and Arginine
Authors: Weir G C , Samols E , Loo S , Patel Y C , Gabbay K H 
Published: September 2013

The isolated perfused canine pancreas with duodenal exclusion was used to examine islet hormone output in response to arginine and exogenous glucagon and insulin. Exogenous glucagon (100 ng/ml) stimulated insulin and somatostatin secretion, which occurred in a biphasic pattern. The insulin response to glucagon was markedly enhanced by increased perfusate glucose, unlike the somatostatin response, which was little affected. The insulin and somatostatin responses were seen between 15 and 45 s after the glucagon stimulus. Pancreatic polypeptide secretion was uninfluenced by exogenous glucagon.
Biphasic release of glucagon, somatostatin, and pancreatic polypeptide was evoked by 10 mM arginine, the responses first being apparent within less than 30 s. Exogenous insulin (50 mU/ml) infused for 10 min had no statistically significant effect on glucagon, somatostatin, or pancreatic polypeptide secretion. This study suggests that these four islet hormones may all be involved in the dynamic mechanisms of nutrient metabolism. In addition, potential intra-islet paracrine effects are identified.
Pharmacogenetics of Tolbutamide Metabolism in Humans
Authors: Scott Joanne , Poffenbarger Phillip L 
Published: September 2013

This study was designed to focus on the genetic control of tolbutamide disposition in humans and to provide insight into the potential for high accrued blood levels in individuals receiving fixed dosage regimens. Tolbutamide was administered intravenously to 42 nondiabetic subjects, eight of their relatives, and to five sets of twins. A ninefold variation in the rate of tolbutamide disappearance from plasma (Kd) was found. This variation was characterized by a trimodal frequency distribution, suggestive of monogenic inheritance and consistent with pedigree analysis, indicating autosomal transmission of rapid and slow inactivation of tolbutamide. A heritability value of 0.995 for Kd indicated little influence of environmental factors on variation of this rate.
Interindividual differences in the binding of 35S-tolbutamide to serum proteins were also assessed. No correlation was found between tolbutamide serum protein binding affinity and Kd. Analysis of the metabolites of tolbutamide in urine samples provided evidence for the microsomal oxidation of the drug to hydroxytolbutamide as the primary site of genetic control.
In conclusion, this study provides evidence for monogenic control of tolbutamide metabolism in man. The results suggest that fixed dosage regimens of this drug, as were prescribed in the controversial University Group Diabetes Program study, might lead to higher accrued blood levels in slow inactivators.
Nutrition and Somatomedin. VIM. The “Somatomedin Inhibitor” in Diabetic Rat Serum is a General Inhibitor of Growing Cartilage
Authors: Phillips Lawrence S , Vassilopoulou-Sellin Rena , Reichard Larry A 
Published: September 2013

Serum somatomedin activity appears to reflect the presence of both somatomedins and “somatomedin inhibitor,” a factor(s) that blunts cartilage stimulation by somatomedins. Although poor growth in uncontrolled diabetes is associated with an increase in inhibitor, suggesting a possible physiologic role, little is known of the interactions between this factor and somatomedins. We examined such interactions by measuring the effects of serum from normal rats (NRS, enriched in somatomedins) and serum from streptozo-tocin-diabetic rats (DRS, enriched in inhibitor) on costal cartilage from hypophysectomized rats. A 48-h exposure of cartilage to NRS resulted in an uptake of sulfate and uridine 125 ± 36% and 59 ± 14% (m ± SEM) above buffer levels, respectively, but addition of DRS to NRS produced sulfate and uridine uptake of 66 ± 3% and 95 ± 2% below buffer, respectively, indicating that chondroitin sulfate and RNA synthesis were both affected. Significant inhibition of uridine uptake (an early cartilage process) occurred as little as 4 h after exposure to DRS, while inhibition of sulfate uptake (a later process) was not found until 20 h. The decrease in isotope uptake following 24 h of exposure to DRS persisted over the next 24 h despite transfer of cartilage to fresh DRS-free medium and addition of NRS during the second 24-h period. When cartilage was incubated with a fixed concentration of DRS and increasing concentrations of NRS, Lineweaver-Burk analysis of both sulfate and uridine uptake indicated that NRS/DRS interactions were noncompetitive.
These results indicate that the inhibitory factor in DRS affects different cartilage processes, produces profound, long-lasting decreases in cartilage activity, and has noncompetitive interactions with somatomedins in NRS. We conclude that somatomedin inhibitor in the serum of diabetic rats is a general inhibitor of growing cartilage that not only blocks stimulation by somatomedins, but also inhibits cartilage metabolism directly.
Genetic Susceptibility to Diabetes Mellitus: the Distribution of Properdin Factor B (Bf) and Glyoxalase (GLO) Phenotypes
Authors: Kirk R L , Theophilus Jaya , Whitehouse S , Court J , Zimmet P 
Published: September 2013

The distribution of phenotypes controlled by two loci on chromosome 6 has been studied in a series of 239 patients with type 1 (insulin-dependent) and 297 patients with type 2 (non-insulin-dependent) diabetes mellitus. At the properdin factor B (Bf) locus there is a significant increase in the frequency of the Bfs1 and BfF1 alleles for type 1 patients, and the combined increase in frequency of Bfs1 and BfF1 in those patients is highly significant. The relative risk for F1 is 6.2 and for F1 and S1 combined is 5.3. These results confirm the association with F1 reported recently by Raum and co-workers in Boston. The two rare alleles Bfs1 and BfF1 are in significant negative disequilibrium with HLA B8.
For the glyoxalase (GLO) locus there is a slight but nonsignificant increase in the frequency of the GLO2 allele, but a significant disturbance in the distribution of the GLO phenotypes for type 2 patients. These results for the GLO alleles may be due to stratification in our series of type 2 patients. Further studies are in progress to test this hypothesis.
Studies of Insulin Binding in Children Using Human Erythrocytes in Small Amounts of Blood
Authors: Kappy Michael S , Plotnick Leslie 
Published: September 2013

We have demonstrated specific insulin binding by the erythrocytes (RBCs) of children.
Complete binding studies were done using as little as 5 ml of blood.
The receptors exhibited competition-inhibition curves and nonlinear Scatchard plots similar to those reported for insulin target tissues, such as the hepatocyte and the adipocyte.
Compared with those from adults, the RBCs from children had significantly greater numbers of insulin receptors per cell (P &lt; 0.05). The total insulin bound by the RBCs from both children and adults, however, was not different over the physiologic range of insulin concentrations. Cord blood RBCs showed greater numbers of receptors per cell than did those from either children or adults; however, the affinity for insulin was similar in both groups. The total amount of insulin bound by cord blood was significantly greater than that in either children (P &lt; 0.01) or adults (P &lt; 0.05) over the physiologic range of insulin concentrations.
The method used to measure insulin binding by erythrocytes had relatively little intra- and interassay variability, and there was little diurnal variation in binding. Storage of heparinized blood at 4°C for 24-36h had no effect on insulin binding by the RBCs. We conclude that the measurement of insulin binding by RBCs from small volumes of blood may be particularly useful in the study of infants and children with disorders of carbohydrate metabolism to elucidate the role, if any, of abnormal receptor function in their condition.