bluuebunny/crossref_metadata_2025_split huggingface dataset:
Postheparin Plasma Lipoprotein Lipase and Hepatic Lipase in Diabetes Mellitus: Relationship to Plasma Triglyceride Metabolism
Authors: Nikkilä Esko A , Huttunen Jussi K , Ehnholm Christian 
Published: September 2013

The activity of two triglyceride Upases was determined by an immunochemical method in the postheparin plasma of 60 diabetic patients and of 47 age- and sex-matched nondiabetic control subjects. The results were related to the type of diabetes, to plasma triglyceride and insulin concentrations, to removal of exogenous fat from the blood, and to turnover of VLDL-triglycerides. The mean postheparin plasma lipoprotein lipase (LPL) activity was decreased by 44 per cent (p &lt; 0.001) in patients with untreated ketotic diabetes and by 20 per cent (P &lt; 0.01) in patients with untreated mild to moderate nonketotic early-onset diabetes. Insulin treatment of ketotic diabetes resulted in a rapid increase in the activity of LPL and decrease in serum triglyceride level, whereas sulfonylurea treatment of non-insulin-requiring diabetics did not significantly influence the enzyme activity. In insulin-treated chronic diabetics the average postheparin plasma LPL activity was not different from that of nondiabetic controls, but some of these patients had high LPL values. In normolipidemic maturity-onset-type diabetics the LPL activity was within normal range, but in those having hypertriglyceridemia the average LPL value was decreased by an average of 26 per cent (P &lt; 0.01).
The LPL activity showed a significant negative correlation with the logarithm of serum triglyceride concentration (r = −0.62) and a positive correlation with fractional removal of Intralipid (r = +0.64) and fractional turnover of VLDL triglyceride (r = +0.40). The activity of LPL was correlated to basal plasma insulin concentration in insulin-deficient diabetics (r = +0.34) but not in patients with maturity-onset-type diabetes. The hepatic lipase (HL) activity of postheparin plasma was similar in diabetics and controls, with the exception of hypertriglyceridemic maturity-onset diabetics, who had higher mean HL activity than the corresponding control group (p &gt; 0.01). The activity of HL was not related to triglyceride removal but showed a significant correlation to VLDL-triglyceride production rate.
On the basis of these results it seems that a deficiency of LPL accounts for a great deal of the elevation of serum triglyceride in insulin-deficient human diabetes but has a smaller role in the pathogenesis of the hypertriglyceridemia that is associated with maturity-onset diabetes. The latter abnormality is caused mainly by an increased secretion of triglycerides into the blood even though a decreased LPL may contribute to development of hyperlipemia in cases with gross elevation of serum triglycerides.
Incidence and Significance of Islet-cell Autoantibodies in Different Types of Diabetes Mellitus
Authors: Prete Gian Franco Del , Betterle Corrado , Padovan Domenico , Erle Giuseppe , Toffolo Antonella , Bersahi Giorgio 
Published: September 2013

Islet-cell (ICA) and organ-specific autoantibodies (OSA) were determined by the indirect immunofluorescence technique in 920 diabetics, 1,159 nondiabetic patients, and 100 young and 100 adult healthy controls with normal glucose tolerance. In control subjects ICA were not detected, and only 20 miscellaneous patients with normal glucose tolerance showed ICA (1.7 per cent). ICA were present in 45.4 per cent of patients with juvenile insulin-dependent diabetes (IDD) during the first six months of disease and in 29.1 per cent of patients between 6 and 12 months of disease onset; ICA presence decreased to 19.2 per cent and 20.6 per cent after one and five years of duration of diabetes.
In patients with maturity-onset IDD, ICA incidence was 19.4 per cent in the first year, 20 per cent between one and five years, and 12.2 per cent after five years of disease. In this group, 64 per cent of ICA-positive patients showed clinical and/or serologie evidence of thyroid, gastric, or adrenal autoimmune disorders.
In sera from young patients with non-insulin-dependent diabetes (J-NIDD), ICA were not detected. In adult patients with the same type of diabetes (M-NIDD) ICA incidence was 9.8, 7, and 8.9 per cent and was not related to the duration of diabetes. Patients with chemical diabetes were divided into two groups (younger and older than 35 years), and ICA incidence was 18.9 and 12.9 per cent, respectively. In two nondiabetic patients, glucagon cell autoantibodies were detected. ICA titers were variable in juvenile IDD of recent onset. Persistent ICA titers, frequently associated with OSA, were observed in the other types of diabetes, with the exception of J-NIDD. ICA may be considered markers of severe beta-cell alteration, with consequent reduction of insulin secretion, even though insulin dependency is sometimes delayed in a few patients.
Lipid Metabolism in Pregnancy: V. Interactions of Diabetes, Body Weight, Age, and High Carbohydrate Diet
Authors: Warth Maria R , Knopp Robert H 
Published: September 2013

Plasma triglycerides increase two-to-three-fold in normal pregnancy. If mechanistically similar to the atherosclerosis-associated hypertriglyceridemias, hypertrigiyceridemia in pregnancy should be exaggerated by diabetes, obesity, and high carbohydrate feeding. A failure to exaggerate would point to a different physiologic mechanism. To study this matter, we measured fasting plasma triglyceride and cholesterol in 38 normal, 22 gestational-diabetic, and 27 overtly diabetic women in the third trimester, measuring the concomitant effects of age and body weight and, in four subjects, high carbohydrate feeding.
Compared with controls, fasting plasma triglyceride and cholesterol were unchanged in gestational diabetics and in 10 of the 27 overtly diabetic pregnant women treated with insulin and diet. However, 17 of 27 diabetic women treated with an estrogen-progestin supplement during gestation had a 36 per cent higher triglyceride and a 15 per cent higher cholesterol than control. Body weight, age, duration of diabetes, or length of gestation could not account for the observations. In non-hormone-treated subjects, regression analysis showed a positive correlation of triglycerides with age but not with body weight. High carbohydrate feeding in pregnancy produced a triglyceride increase (mean±S.D.) of 9±19 per cent in whole plasma and 17±13 per cent in very-low-density Upoprotein. Respective postpartum increases were 41 and 68 per cent, similar to the responses reported in nonpregnant individuals.
Conclusion: Lack of a major effect of diabetes, body weight, and high carbohydrate feeding on blood lipids in gestation distinguishes pregnancy from the atherosclerosis-associated hypertriglyceridemias and points to a different physiologic control mechanism.
Pancreatic Islet-cell Antibodies in Diabetes Mellitus Correlated with the Duration and Type of Diabetes, Coexistent Autoimmune Disease, and HLA Type
Authors: Irvine W J , McCallum C J , Gray R S , Campbell C J , Duncan L J P , Farquhar J W , Vaughan H , Morris P J 
Published: September 2013

In a study of 972 patients with diabetes mellitus, humoral pancreatic islet-cell antibodies (I.C.Ab.) were detected in highest prevalence in insulin-treated diabetics with (38 per cent) and without (22 per cent) associated overt organ-specific autoimmune disease (A.I.D.) where consideration was not given to the duration of diabetes. They were also detected in 8 per cent of diabetics treated with oral bypoglycemk agents (O.H.A.), but not in diabetics requiring diet alone and in only 0.5 per cent of 434 control subjects. Six per cent of 522 patients with overt organ-specific A.I.D. but not diagnosed to be diabetic had I.C.Ab.s. I.C.Ab.s were present in the sera of 2 per cent of 157 first-degree relatives of I.C.Ab.-positive subjects.
In insulin-treated diabetics and, to a lesser extent, in diabetics not requiring insulin, the prevalence of humoral I.C.Ab. was strongly dependent on the duration of the diabetes, being 60 per cent during the first year from diagnosis in the insulin-treated group and falling to 20 per cent at two to five years and to 5 per cent at 10–20 years. The prevalence of I.C.Ab. in insulin-treated diabetics showed no correlation with the patient's age at the time of testing when the duration of diabetes was taken into account.
Diabetics who did not require insulin for treatment but who were I.C.Ab.-positive showed a significant tendency to subsequently require insulin and to have a higher prevalence of other autoantibodies than insulin-independent diabetics who were I.C.Ab.-negative.
Persistence of I.C.Ab. for more than five years from diagnosis of diabetes was associated with coexistent overt organ-specific A.I.D. and with HLA-B8, A1, and A1 + B8.
Investigation of Insulin Sensitivity in Treated Subjects with Ketosis-prone Diabetes Mellitus
Authors: Ginsberg LCDR Henry N 
Published: September 2013

Two similar intravenous infusion techniques have been utilized to investigate insulin sensitivity in young subjects with recent-onset ketosis-prone diabetes mellitus. All subjects presented initially with mild to moderately severe ketoacidosis and had been treated with daily insulin therapy for two to eight weeks at the time of study.
Six diabetics and 10 normal subjects (group A) received intravenous infusions of glucose (6 mg./kg./min.), insulin (80 mU./min.), epinephrine (6 μg./min.), and propranolol (0.08 mg./min.) for ISO minutes. Steady-state plasma glucose (SSPG) and insulin levels (SSPI) were reached by 90 minutes and maintained through the end of the study. As all subjects achieve similar SSPI while simultaneously receiving similar glucose loads, the SSPG can be used to measure individual insulin sensitivity. Under these conditions the diabetics in group A had a mean SSPG (± S. E.) of 99 ± 26 mg./lOO ml., which was not different from the level of 98 ± 14 mg./100 ml. for their control subjects. Six diabetics and six normal subjects (group B) received infusions of only glucose (6 mg./kg./min.) and insulin (80 mU./min.). Similar SSPI levels were attained in both the diabetic and control subjects, and their mean SSPG (± S.E.) levels were not significantly different (83 ± 13 vs. 61 ± 6mg./100 ml.).
One diabetic in group A and two diabetics in group B had SSPG levels above the highest values measured in their control groups. However, all three had markedly elevated fasting plasma glucose levels on the day of study. In contrast, nine well-controlled diabetics had normal insulin sensitivity. These results suggest that well-controlled subjects with ketosis-prone diabetes mellitus have normal sensitivity to insulin.
2,3-Diphosphoglycerate, Nucleotide Phosphate, and Organic and Inorganic Phosphate Levels During the Early Phases of Diabetic Ketoacidosis
Authors: Kanter Y , Gerson J R , Bessman A N 
Published: September 2013

The relation between serum and red blood cell (RBC) inorganic phosphate levels, RBC 2,3-diphosphoglycerate (2,3-DPG) levels, RBC nucleotide phosphate (Pn), and RBC total phosphate (Pt) levels were studied during the early phases of treatment and recovery from diabetic ketoacidosis (DKA).
A steady drop in serum inorganic phosphate was found during the first 24 hours of insulin treatment and was most profound at 24 hours. No statistically significant changes (P&gt;0.05) were found in red cell inorganic phosphate or nucleotide phosphate levels during the 24-hour study period. The levels of total red cell phosphate were lower in this group of patients than in nonacidotic diabetic subjects and decreased slightly after 24 hours of treatment. The red cell 2,3-DPG levels were low at the initiation of therapy and remained low during the 24-hour study period. Glucose, bicarbonate, lactate, and ketone levels fell in linear patterns with treatment.
In view of the current evidence for the effects of low 2,3-DPG on oxygen delivery and the relation of low serum phosphate levels to RBC glycolysis and 2,3-DPG formation, this study reëmphasizes the need for phosphate replacement during the early phases of treatment of DKA.
Mechanism of Hypoglycemia Observed in a Patient with Insulin Autoimmune Syndrome
Authors: Ichihara Kikuo , Shima Kenji , Saito Yoshikazu , Nonaka Kyohei , Tarui Seiichiro , Nishikawa Mitsuo 
Published: September 2013

A 21-year-old female patient complaining of frequent hypoglycemie attacks in the presence of a large amount of circulating insulin-binding antibodies without prvious known immunization is described.
In order to clarify the possible mechanism of the hypoglycemie attacks occurring in this new syndrome, changes in plasma glucose, plasma total and free immunoreactive insulin (IRI), and C-peptide immunoreactivity (CPR) levels were investigated in the patient before, during, and after a three-hour glucose infusion. The character of her antibodies was also examined. An abrupt discontinuation of the glucose infusion caused a sharp decline in the plasma glucose level, reaching a nadir of 30 mg./100 ml. at 270 minutes; then she became unconscious. A huge amount of total IRI of 2,834 μU./ml. was registered at 180 minutes, while the peak value of free IRI of 208 /μU./ml. was observed 45 minutes after the cessation of the glucose infusion. Plasma CPR was increased from high basal level, 19.6 ng./ml., to the maximum level of 29.2 ng./ml. The maximum insulin-binding capacity of IgG in the patient's serum was 6.25 mU./ml. The antibody-combining site was homogeneous, showing one high-affinity site (K: 1.1 × 109M−1).
Neither the prolonged fasting nor the administration of tolbutamide induced the hypoglycemie attack in the patient.
The hypoglycemia may be explained by an unduly excessive amount of insulin liberated from a large pool of bound insulin irrespective of blood sugar level. The cause of the antibody production is also discussed.
Intravenous Insulin Causing Loss of Intravascular Water and Albumin and Increased Adrenergic Nervous Activity in Diabetics
Authors: Gundersen H J G , Christensen N J 
Published: September 2013

Blood pressure, heart rate, plasma norepinephrine, forearm blood flow, plasma volume, plasma albumin, blood glucose, and plasma epinephrine were measured in six diabetic patients without neuropathy in the supine position and during feet-down tilting for seven minutes. The experiments were repeated after intravenous (i.v.) injection of 6 to 8 U. of insulin.
The mean blood glucose concentration averaged 205 ± 14 (S. E. M.) mg./100 ml. in the control experiment and had decreased by 97 ± 17 mg./100 ml. 45 minutes after the injection of insulin. None of the patients had hypoglycemia, and plasma epinephrine did not increase.
There was no change in arterial blood pressure after insulin was given either in the supine position or after tilting. The heart rate averaged 64 ± 5 beats per minute in the control experiment and had increased by 7 ± 2 beats per minute 40 minutes after the injection of insulin (2p = 0.035). The rise in heart rate In response to tilting was statistically significantly greater after administration of insulin (2p = 0.0064).
Plasma norepinephrine averaged 0.17 ± 0.03 ng./ml. in the control experiment and had increased by 70 ± 24 per cent 45 minutes after the i.v. injection of insulin (2p = 0.045). The rise in plasma norepinephrine in response to tilting was statistically significantly greater after the injection of insulin (2p = 0.017).
Forearm blood flow decreased from 2.13 ± 0.29 ml./l00 ml. per minute in the control experiment to 1.63 ± 0.32 ml./100 ml. per minute 40 minutes after the injection of insulin (2p = 0.011). Plasma volume averaged 3,061 ± 67 ml. before injection of insulin and had decreased by 265 ± 59 ml. 45 minutes after insulin was given (2p = 0.011). The intravascular mass of albumin averaged 118 ± 3 gm. and 109 ± 3 gm. before and 45 minutes after the administration of insulin, respectively (2p = 0.017).
There was a dose correlation between the relative increase in plasma norepinephrine in the supine position and the relative decrease in plasma volume after the injection of insulin (r = −0.95, 2p = 0.013).
It is concluded that i.v. injection of insulin results in an increased adrenergic nervous activity that is due to a decrease in plasma volume. The effect of insulin is accompanied by a significant reduction in the intravascular pool of albumin.
These observations may explain the fact that patients with abnormal cardiovascular reflexes are unable to maintain arterial blood pressure, especially in the upright position, after the i. v. injection of insulin.
The observed decrease in plasma volume after the administration of insulin was much larger than could be expected from the decrease in blood glucose concentration and the ensuing decrease in plasma osmolality.
It is suggested that insulin either directly or secondarily to its metabolic effects may alter the function or the volume of the endothelial cells and thereby increase the transfer of fluid and albumin out of the vascular system.
6-Phosphogluconate/Glucose-6-Phosphate Ratio in Rat Pancreatic Islets During Inhibition of Insulin Release by Exogenous Insulin
Authors: Akhtar Muhammad S , Verspohl Eugen , Hegner Dietmar , Ammon Hermann P T 
Published: September 2013

Inhibition of glucose-stimulated insulin release by exogenous insulin has been demonstrated in pancreatic islets to be associated with a decrease of the NADPH/NADP ratio and the pentosephosphate cycle activity.
Batches of five islets were incubated for 15 and 90 minutes in 1 ml. of KRB buffer with 2 per cent albumin containing 3mg/.ml. glucose and 0, 200, 400, or 800 μU./ml. of rat insulin, and the glucose-6-phosphate (G6P) and 6-phosphogluconate (6PG) contents were determined by enzymatic cycling.
In response to a rise in the concentration of insulin, the 6PG/G6P ratio decreased. A close relationship was observed between this decrease of 6PG/G6P ratio and the net insulin release, the absolute rate of glucose oxidation via the pentose phosphate cycle, and the NADPH/NADP ratios measured under similar conditions. The results suggest that exogenous insulin, directly or indirectly, regulates the pentose cycle activity in the pancreatic islets at the G6P dehydrogenase step.
The Immediate Insulin-secretory Response of the Rat Pancreas to Glucose Compared with Tolbutamide and Other Secretagogues
Authors: Lenzen Sigurd 
Published: September 2013

Insulin secretagogues induced characteristic secretory responses of the pancreas. While tolbutamide provoked an immediate insulin secretory response of the perfused rat pancreas, after a short delay insulin secretion appeared in response to glyceraldehyde, glucose, and mannose after different characteristic latent periods. Glucose and tolbutamide competed for insulin from the same rapidly available hormone pool during the immediate insulin-secretory response of the perfused pancreas. The mechanism of their secretory action differed.
There was a latent period between arrival of glucose at the pancreatic β-cells and the insulin-secretory response when the perfu-sate was switched from a medium without glucose to a medium with 16.7 mM glucose. However, when the preperfusion medium contained a substimulatory glucose concentration, this latent period was diminished or nearly abolished. The increment in glucose concentration necessary for insulin release was reduced con-comitantly. The ability of glucose to sensitize pancreatic β-cells was concentration-dependent and time-dependent. Only mannose was able to substitute for glucose in its capacity to virtually abolish the latent period. Glyceraldehyde, dihydroxyacetone, and leucine only reduced the latent period. L-glucose, 3-O-methylglucose, fructose, and pyruvate were ineffective. Tolbutamide desensitized the β-cell to glucose stimulation and prolonged the latent period.
It is proposed that both glucose and tolbutamide initiate insulin secretion by interaction with a common receptor site. They differ, however, in that glucose but not tolbutamide sensitizes pancreatic β-cells. Tolbutamide cannot fully replace glucose.
Syntheses of C-peptides and Human Proinsulin
Authors: Yanaihara Noboru , Yanaihara Chizuko , Sakagami Masanori , Sakura Naoki , Hashimoto Tadashi , Nishida Toshinobu 
Published: September 2013

Syntheses of human, dog, rat, and duck C-peptides and their analogues and preliminary results on the total synthesis of human proinsulin are described.
In the syntheses of the C-peptides, chain elongation was performed exclusively by the azide-fragment condensation method in solution. The synthetic human, dog, rat, and duck C-peptides and their analogues were proved to be homogeneous by several analytic means. With these synthetic peptides, radioimmunoassay systems for dog, rat, and duck C-peptides were developed.
For the total synthesis of human proinsulin, 10 protected peptide hydrazides were prepared, and the linearly protected hexaoctacontapeptide having the proposed sequence of human proinsulin was constructed by the azide-fragment condensation method in solution starting from the C-terminal undecapeptide (HP 75–86). After deblocking of the α-amino protection, the partially protected hexaoctacontapeptide was treated with sodium in liquid ammonia. The ensuing sulfhydryl form was converted to the S-sutfonate form, which was reduced and then air-oxidized. The oxidized material was purified by gel filtration on Sephadex G-50 (fine) followed by ion-exchange chromatography on DEAE-cellulose. The crossreactivity in the insulin radioimmunoassay of the ensuing product was 62.5 per cent of porcine proinsulin on a weight basis at B/B0 = 60 per cent.
Acid hydrolysis and amino acid analysis of this product gave the theoretically expected ratios. In addition, this peptide, as well as the S-sutfonate form of the hexaoctacontapeptide, showed displacement curves superimposable on that of synthetic human C-peptide on an equimolar basis in the human C-peptide radioimmunoassay (antiserum 527). These results confirm the synthesis of human proinsulin.
C-peptide Immunoreactivity (CPR) in Urine
Authors: Kuzuya Takeshi , Matsuda Ayako , Sakamoto Yoshikazu , Tanabshi Shinobu , Kajinuma Hiroshi 
Published: September 2013

Human urinary C-peptide immunoreactivity (CPR) was measured by a double-antibody radioimmunoassay using synthetic human C-peptide. Urine CPR was stable as long as one year, if stored frozen. Urine CPR was eluted by gel filtration as a single peak in the region that corresponded to 125I-labeled C-peptide. Even in a patient with insulin antibody whose serum contained a CPR fraction with higher molecular weight, urine CPR was eluted in its expected region.
Normal subjects excreted 81 ± 36 μg. CPR per day. Urine CPR excretion was very low in juvenile-onset diabetics, variable in adult-onset diabetics and liver disease patients, and increased in patients on corticosteroid treatment. Diurnal changes and a 50-gm. glucose tolerance test revealed that urine CPR excretion rate increased in parallel with plasma CPR levels. The responses of diabetic patients were smaller and more sluggish. Urine CPR excretion tended to be decreased in patients with renal diseases and extremely low in those on regular hemodialysis. CPR was positively correlated with serum creatinine. Urine CPR was not increased in patients with marked β2-microglobulin excretion.
Highly significant correlations were observed between 24-hour urine CPR values and fasting plasma CPR or summed CPR after glucose load. Thus, urine CPR seems to provide a good means to assess B-cell function, and it is particularly suitable to monitor B-cell function continuously or when multiple blood samplings are not practical. Continuous measurement of daily urine CPR in diabetic patients on glibenclamide treatment revealed that improvement of blood sugar control could occur without preceding increases in total daily B-cell secretion.