bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myoinositol Metabolism in Diabetes Mellitus: Effect of Insulin Treatment
Authors: Clements Rex S , Reynertson Richard 
Published: September 2013

The metabolism of myoinositol has been studied in 10 nondiabetic subjects and in six patients with diabetes mellitus before and after insulin therapy. While dietary myoinositol intake and fecal myoinositol excretion were similar in both groups, urinary myoinositol excretion was increased 10-fold in the untreated diabetic and accounted for a significant fraction of his dietary myoinositol intake. Insulin treatment restored the urinary myoinositol excretion toward normal. Despite increased myoinositol excretion, plasma myoinositol concentrations were significantly higher in the diabetics following the ingestion of a standard diet or of a 3.0-gm. myoinositol load. This abnormality in oral myoinositol tolerance was also corrected by insulin treatment. The size of the rapidly equilibrating myoinositol pool was significantly decreased in the untreated diabetic and returned to normal following a brief period of insulin treatment.
The elevated plasma myoinositol concentrations observed following myoinositol ingestion in the uncontrolled diabetic presumably represents a combination of enhanced gastrointestinal absorption and impaired intracelhilar transport of myoinositol. The decreased space of distribution of myoinositol also suggests an impairment of intracellular myoinositol transport in the untreated diabetic. These observations are consistent with the speculation that hyperglycemia may condition a widespread relative intracellular myoinositol deficiency in man and suggest that restoration of normal intracellular myoinositol concentrations might prove to be of benefit in the prevention and treatment of certain of the complications associated with human diabetes mellitus.
Carbohydrate Metabolism and Pancreatic Islet-cell Function in Thalassemia Major
Authors: Costin Gertrude , Kogut Maurice D , Hyman Carol , Ortega Jorge A 
Published: September 2013

To investigate the development of diabetes mellitus in patients with thalassemia major, plasma glucose and immunoreactive insulin (IRI) levels following oral glucose and intravenous tolbutamide and glucose disappearance rates following intravenous insulin were measured in 10 patients before and during five years on a high transfusion program (HTP). Plasma immunoreactive glucagon (IRG) levels following oral glucose, intravenous insulin, and arginine were measured during the sixth year. Serial percutaneous liver biopsies were performed on seven patients.
The oral glucose tolerance tests (OGTT) and mean peak IRI levels were normal in nine of 10 patients before HTP. After HTP was begun a progressive deterioration of OGTT occurred despite normal IRI levels. Following tolbutamide, the mean per cent fall in plasma glucose in the patients before HTP was significantly less than in controls (p &lt; 0.01) and similar to that of controls during five years of HTP in spite of higher than normal peak IRI levels.
Of seven survivors after six years of HTP, three had normal OGTT and four had chemical diabetes; mean peak IRI levels were normal, but fasting IRG levels were significantly higher than in controls (p &lt; 0.05). In all seven patients, plasma IRG failed to increase following insulin-induced hypoglycemia and was significantly higher than in controls after arginine (p &lt; 0.01); after oral glucose, plasma IRG fell significantly below that of fasting only in the patients with chemical diabetes (p &lt; 0.03). Following intravenous insulin, the mean per cent fall in glucose before and during HTP was significantly less than in controls (p &lt; 0.01). Hemosiderosis and cirrhosis were present in all biopsied patients. Four patients died; two had chemical and two had nonketotic insulin-dependent diabetes.
These data suggest that diabetes mellitus occurs frequently in patients with thalassemia on HTP and that insulin resistance and hyperglucagonemia, possibly due to cirrhosis, are important etiologic factors.
Effect of Ethanol on Stimulus-induced Insulin Secretion and Glucose Tolerance: A Study of Mechanisms
Authors: Shah Jayendra H , Wongsurawat Nirandon , Aran Peter P 
Published: September 2013

The effect of ethanol on stimulus-induced insulin secretion was studied, and possible mechanisms were examined in fasting unanes-thetized and unrestrained rats with indwelling jugular and aortic catheters. Glucose (150 mg.) or tolbutamide (10 mg.) was given rapidly, i.v., one hour after a gavage of ethanol or saline (control). Acutely, ethanol treatment caused marked inhibition of glucose-induced insulin secretion and impaired glucose disappearance rate. Tolbutamide-induced insulin secretion was also significantly inhibited, and decline in glucose was significantly less in ethanol-treated rats. In response to ethanol, serum calcium concentration significantly declined for two hours.
In another study, an ethanol metabolite, acetate (0.4 μmole/min.) or vehicle (control) was infused for 60 minutes prior to 150 mg. glucose pulse. Acetate priming significantly potentiated glucose-induced insulin secretion and also improved glucose tolerance.
It is proposed that (1) ethanol in vivo acutely induces hypocalcamie, which inhibits glucose- and tolbutamide-induced insulin secretion—which, in turn, causes glucose intolerance and prevents tolbutamide-induced hypoglycamie. (2) Acetate might be the actual potentiating influence on glucose-induced insulin secretion observed several hours after ethanol treatment.
A Test of the Hypothesis that the Rate of Fall in Glucose Concentration Triggers Counterregulatory Hormonal Responses in Man
Authors: DeFronzo Ralph A , Andres Reubin , Bledsoe Turner A , Boden Gunther , Faloona Gerald A , Tobin Jordan D 
Published: September 2013

The hypothesis that the rate of fall in glucose concentration triggers counterregulatory hormonal responses was tested in five subjects following one hour of sustained hyperglycemie. Despite a rapidly falling blood glucose concentration, no increase in plasma growth hormone, Cortisol, glucagon, or catecholamines occurred as long as the blood glucose concentration remained above fasting levels. Plasma growth hormone, cor tisol, and catecholamines were not released until the mean blood glucose reached 28 mg./100 ml., 39 mg./100 ml., and 39 mg./100 ml., respectively, below the fasting level.
Plasma glucagon was suppressed during the period of hyperglycemia. As the blood glucose concentration fell below basal levels, a progressive increase in glucagon occurred. Plasma glucagon returned to fasting values when the nadir in blood glucose was attained. During the period of rapidly falling blood glucose, only plasma insulin showed any change; its response lagged behind the decline in blood glucose. By the time the fasting glucose level was attained, the plasma insulin was still almost three times the basal level. We concluded that under our experimental conditions the rate of fall in blood glucose and the degree of hypoglycemie achieved is primarily determined by the plasma insulin concentration.
Potentiation of the Hepatic Action of Insulin by Chlorpropamide
Authors: Blumenthal Stanley A 
Published: September 2013

In perfused livers of fed rats, chlorpropamide inhibits glucagon-stimulated glucose production by augmenting the action of insulin. This effect is associated with a decrease in cyclic AMP accumulation in liver and perfusate.
Alterations in glucose production appear to correlate more closely with changes in the amount of cyclic AMP in the perfusate than with changes in intrahepatic concentration of nucleotide.
Potentiation by chlorpropamide of the hepatic action of insulin does not require administration of the drug prior to perfusion. Further, it is demonstrable at concentrations of insulin and glucagon (10−11M) that approximate the normal plasma levels of these hormones.
Effects of Fasting on Insulin Secretion, Islet Glucose Metabolism, and the Cyclic Adenosine 3',5'-Monophosphate Content of Rat Pancreatic Islets In Vitro
Authors: Wolters Gerrit H J , Konijnendijk Willem , Bouman Paul R 
Published: September 2013

Fasting for 24 hours inhibits glucose-induced insulin secretion from isolated rat pancreatic islets. At glucose 15 raM the inhibition is only present during the initial 30-45 minutes of stimulation. It decreases at higher glucose concentrations and disappears at glucose 37.5 mM.
In islets of fed rats, 15 minutes of stimulation with glucose 15 mM induced an almost threefold rise of islet cyclic adenosine 3',5'-monophosphate (cAMP). Both this effect and the secretory response were inhibited by about 65 per cent after 24 hours of fasting and almost completely by 72 hours of food deprivation. Fasting for 24 hours also caused a 56 per cent inhibition of the rise of islet cAMP and insulin secretion induced by D-glyceraldehyde 10 mM, but the inhibition was not further enhanced by 72 hours of fasting. Fasting for 24 and 72 hours did not significantly inhibit the islet cAMP response to 15 minutes of stimulation with glucose 37.5 mM.
Fasting for 24 hours impaired neither islet glucose oxidation (14CO2 production) nor over-all glucose utilization (production of 3H-water from [5-3H] glucose) during the initial 30 minutes of stimulation with glucose. After 72 hours of fasting, both over-all glucose utilization and glucose oxidation were reduced by 25 per cent.
These findings suggest that inhibition of the islet cAMP response is a primary factor in the early (24 hours) fasting-induced impairment of the insulin secretory response to glucose stimulation at 5-15 mM. Inhibition of islet glucose metabolism seems to be an independent additional phenomenon that becomes manifest after longer periods of food deprivation.
HLA System in Japanese Patients with Diabetes Mellitus
Authors: Kawa A , Nakazawa M , Sakaguchi S , Nakamura S , Kono Y , Hazeki H , Kanehisa T 
Published: September 2013

Seventy-eight Japanese diabetics were HLA-typed, with special reference to age at onset, insulin dependency, and family history.
HLA-A9, B5, and BW40 were increased, but Al, A3, and B8, which are found frequently among Caucasians, were almost absent among Japanese healthy controls as well as diabetics.
J-l, a Japanese specific subclass of BW22, was significantly increased in juvenile-onset diabetics as compared with controls or diabetics with late onset. J-l was also increased in the diabetics with insulin dependency and/or positive family history. But the association of J-l with juvenile-onset diabetes mellitus was found to be the strongest. A tendency to a decrease in B5 was also observed in Japanese diabetics with juvenile onset, but this did not reach statistical significance as far as corrected P was concerned. These results showed that genetic markers for diabetes mellitus, especially that with juvenile onset, were different among Japanese from those found among Caucasians.
There is ample evidence to indicate a race specificity in HLA phenotypes in diabetics as well as in controls.
These findings also strongly suggest that juvenile-onset diabetes mellitus is a disease entity in itself and different from late-onset diabetes mellitus in origin and pathogenesis.
C-peptide Response to Glucagon: A Test for the Residual β-cell Function in Diabetes Mellitus
Authors: Faber O K , Binder C 
Published: September 2013

Pancreatic β-cell secretory activity was measured in 17 patients with insulin-dependent diabetes mellitus of less than 19 months' duration and in 10 nondiabetic subjects by means of the peripheral plasma C-peptide response to 1 mg. of glucagon i.V. The C-peptide response to a meal was also measured in the diabetic patients.
Residual β-cell function was present in all the diabetic patients as indicated by significant amounts of C-peptide in plasma. Significant increases in C-peptide were observed in 16 after glucagon stimulation and in 15 after the meal. Both absolute and relative increase in C-peptide were reduced in the diabetic patients. The increase in C-peptide was correlated to the fasting C-peptide concentration both after glucagon (r = 0.86, p &lt; 0.001) and after the meal(r = 0.66, p &lt; 0.01). The responses to the meal and to glucagon were correlated (r = 0.77, p &lt;0.005), indicating a high predictive value of the glucagon test as to how the β-cells will respond during normal daily life.
Nesidioblastosis: The Pathologic Basis of Persistent Hyperinsulinemic Hypoglycemia in Infants: Morphologic and Quantitative Analysis of Seven Cases Based on Specific Immunostaining and Electron Microscopy
Authors: Heitz Philipp U , Klöppel Günter , Häcki Walter H , Polak Julia M , Pearse A G Everson 
Published: September 2013

Seven surgical specimens of pancreas, obtained at laparotomy from infants suffering from persistent hyperinsulinemic hypoglycemia, were analyzed by qualitative and quantitative immunocytochemistry and by electron microscopy. In five cases a multifocal ductuloinsular proliferation, in one a focal adenomatosis, and in one a solitary encapsulated nodule (adenoma) were observed. Combinations of the different patterns of proliferation were seen in six cases. Budding off from the ductular epithelium and interposition of endocrine cells between ductular epithelial cells were prominent features common to all cases. An almost fivefold increase of the mean total area occupied by endocrine tissue was found over that of age-matched controls. Four cell types were seen to participate regularly in the proliferation, and their ratios were remarkably constant in all cases, mean figures being 62:21:9:8 per cent for B:A:D:D1 cells, respectively. The ratio of B cells per total endocrine area in nesidioblastosis was very close to that per islet of the controls (62:59 per cent).
Since common features were found in all or in the majority of cases, it is suggested that the various patterns of proliferation are merely morphologic variations of the same basic defect. Nesidioblastosis may result from inappropriately controlled development of the endocrine pancreas that is not arrested but carries on beyond birth and during infancy. The application of specific immunocytochemistry as a necessity for full appreciation of the extent of endocrine proliferation is stressed.
Nutrition and Somatomedin: III. Diabetic Control, Somatomedin, and Growth in Rats
Authors: Phillips Lawrence S , Orawski Arthur T 
Published: September 2013

Observations of a growth hormone-resistant decrease in somatomedin activity associated with conditions of insulinopenia suggest that somatomedin and growth might be related to metabolic control in diabetes mellitus. We examined this relationship by comparing measures of insulin effect with serum somatomedin activity (porcine cartilage bioassay), cartilage growth activity (SO4 uptake in vitro), and change in body weight in streptozotocin-diabetic rats. A range of metabolic control was produced by administration of varied quantities of insulin over twoand four-day periods. Serum somatomedin activity was significantly correlated with serum glucose and Β-hydroxybutyrate (r = −0.69 and −0.76, respectively, p &lt;0.001 for both) but not with free fatty acids. A level of serum glucose &lt;240 mg./dl. or /3-hydroxybutyrate &lt;1.3 mM at sacrifice was generally associated with serum somatomedin activity within the normal range. Urine glucose levels less than 0.1 gm./24 hr. were also associated with normal serum somatomedin activity. Insulin therapy sufficient to provide β-hydroxybutyrate less than 1.3 mM at sacrifice was associated with levels of serum somatomedin activity and cartilage growth activity comparable to those of normal animals and significantly greater than those of untreated diabetic animals. This level of insulin effect also permitted diabetic animals to gain weight at a rate comparable to that of normal animals.
These studies demonstrate a close relationship between insulin efficacy, serum somatomedin activity, cartilage growth activity, and weight gain and support the hypothesis that through somatomedin, insulin may contribute to growth.
Insulin, C-peptide, and Proinsulin in Nondiabetics and Insulin-treated Diabetics: Characterization of the Proinsulin in Insulin-treated Diabetics
Authors: Heding Lise G. 
Published: September 2013

Immunoreactive insulin (IRI), C-peptide, and proinsulin were determined in 46 fasting nondiabetic persons. The means ± S.D. for IRI, C-peptide, and proinsulin (in pmol/ml.) in the 46 nondiabetics were 0.054 ± 0.027, 0.39 ± 0.12, and 0.014 ± 0.009, respectively. The molar ratio between C-peptide and IRI varied from 4.0 to 16.7, with a mean value of 7.9 ± 3.4. Proinsulin constituted 5–36 per cent of IRI, with a mean of 20 ± 10 per cent.
Sera from 24 diabetics aged 17–67 years treated with conventional crystalline insulin for durations of from one to 29 years (mean: 15 years), all of whom had circulating insulin antibodies, were extracted with acid ethanol. Total IRI varied from 2.0 to 22.6 pmol/ml. C-peptide was detectable in only three patients (0.05, 0.08, and 0.15 pmol/ml.). In contrast, human proinsulin was found in all patients and ranged from 0.09 to 9.4 pmol/ml., corresponding to 1 to 45 per cent of total IRI. Species-specific immunoassays for bovine and porcine proinsulin revealed the presence of bovine proinsulin in 23 of the patients (mean 0.36 ± 0.20 pmol/ml.) and porcine proinsulin in eight patients (mean 0.15 ± 0.13 pmol/ml.). Total proinsulin constituted 5 to 64 per cent, mean 22 per cent, of total IRI, while human proinsulin amounted to 1 to 45 per cent, mean 10 per cent, of IRI. Although no insulin secretion could be detected in 21 of the patients, as judged by the amount of C-peptide, the B-cell was still able to secrete proinsulin. Insulin antibodies bind a portion of the secreted proinsulin, thus prolonging its half-life and increasing its concentration in serum.
Clinical Evaluation of Metabolic Control in Diabetes
Authors: Molnar George D 
Published: September 2013

This review examines the current status of the clinical evaluation of diabetic control. The assessment of the patient's symptoms and signs is important but requires laboratory confirmation. Major metabolic derangements usually occur before their clinical detection is feasible.
To be complete, the laboratory assessment of diabetic control should include the insulin concentration in blood or urine. At present insulin and other hormones assays have played mainly an investigative role.
Glucose measurements in blood and urine continue to be the standards for evaluation of diabetic control. Glucose tolerance tests or carefully timed preprandial and postprandial plasma glucose measurements on several successive days under consistent conditions of diet and exercise provide data for adequate evaluation of diabetic control. The addition of urinary glucose monitoring to the blood sampling makes the evaluation more complete. Glucose variability measurements in blood and/or urine provide useful data for characterizing patients, for comparing them with other diabetics, with nondiabetic normals, and with themselves from time to time.
Despite their limitations, urine glucose tests are valuable and worth evaluating so as to provide for each patient the most appropriate method of testing. Methods are described for screening patients for atypical blood-to-urine glucose relationships (“renal glucose threshold”) and for estimating such thresholds.
Among lipid metabolic indices of insulin deficiency the urinary ketone bodies are the most commonly measured in clinical medicine. Triglycerides and cholesterol elevations may in part reflect disturbed diabetic control and may warrant a trial of intensified antidiabetic therapy.
The protein metabolic changes of diabetes during hyperglycemia are measurable as decreased levels of plasma alanine and increased levels of branched-chain amino acids. By sensitive quantitative methods, albuminuria is also demonstrably increased during impaired diabetic control. Improved diabetic regulation restores these protein abnormalities toward normal. These newer refinements for evaluating diabetic control await clinical application.
Glycosylation of hemoglobin, identifiable by an increased proportion as hemoglobin A1c, is of special interest as a longer-term indicator of hyperglycemia.
As clinical interest in more complete normalization of diabetic metabolic changes is intensifying, a wider array of methods are becoming available for determining the degree to which metabolic control is normalized.
Islet Cell Survival Determined by Morphology An Immunocytochemical Study of the Islets of Langerhans in Juvenile Diabetes Mellitus
Authors: Gepts W , De Mey J 
Published: September 2013

The cytologic composition of the pancreatic islets of 58 insulin-dependent diabetics with age of onset of the disease before the age of 40 and a duration of from a few days to 37 years was studied with the aid of Sternberger's immunocytochemical method. Four types of islet cells were stained with specific antisera: β cells (insulin), α cells (glucagon), D cells (somatostatin), and PP cells (pancreatic polypeptide).
β cells were found in 14 of 16 recent-onset cases, in seven of 14 patients having diabetes for less than 11 years, and in five of 28 patients in whom the disease had been present for a longer time. In all these cases, the number of β cells was well below normal. They showed cytologic features of functional hyperactivity.
The majority of the islets, even in recent-onset cases, were devoid of β cells and were composed of thin cords of islet cells. Immunocytochemical staining revealed that, contrary to the classic opinion, these cells are not inactive but are actively secreting glucagon or somatostatin. In many long-term juvenile diabetics, the glucagon-containing α cells appeared very numerous, but it remains to be ascertained whether this represents an apparant or a true hyperplasia.
Insulitis was found in 11 of the 16 recent-onset cases. In one case, the lymphocytic infiltration was found only in islets containing β cells but was strikingly absent in the islets composed of glucagon-, somatostatin-, and PP-cells.
Images of islet regeneration, with neoformation of β cells and other islet-cell types from centroacinar and ductular cells could still be detected focally in a few recent-onset cases. With a disease of longer duration, an atypical type of islet regeneration, originating in the epithelium of small- and medium-sized ducts, becomes more prevalent and produces islets solely composed of PP cells.