bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Functional State of Sympathetic Nerves in Spontaneously Diabetic Mice
Authors: Giachetti Antonio 
Published: September 2013

I investigated biochemical parameters of sympathetic nerve function in spontaneously diabetic mice (C57 BL/KsJ db/db) and in their lean littermates. The concentration of norepinephrine (NE) in organs innervated by sympathetic nerves was significantly reduced in the heart, kidney, and salivary glands of mice (24 weeks old) with severe diabetic-like symptoms (blood glucose &gt; 300 mg./100 ml.). In the spleen, vas deferens, and adrenal glands of the same animals the NE levels were not changed in relation to control. Other measurements of NE in young (six weeks old) diabetic mice revealed no differences between diabetic and nondiabetic controls.
The turnover of NE, a measure of the functional state of sympathetic nerves, decreased significantly in the heart and salivary glands of 24-week-old mice but remained unchanged in the kidney and spleen. In young, diabetic mice the rates of NE turnover in several organs were similar to those found in age-matched controls. The hearts of 24-week-old diabetic mice contained significantly less dopamine-β-hydroxylase (DBH), an intraneuronal enzyme active in the terminal step of NE biosynthesis. The kidney of the same animals was hypertrophic and showed a massive elevation of monoamine oxidase (MAO), an enzyme that degrades NE to inactive products.
Other experiments showed that the regeneration of sympathetic neurons that follows the reversible chemical denervation with 6-hydroxydopamine was comparable in diabetic and nondiabetic animals. It appears that mice with spontaneous diabetes show changes of sympathetic nerve function similar to those noted in diabetic patients with autonomic neuropathy.
Serum Lipids and Lipoproteins in Insulin-treated Diabetes: Demonstration of Increased High Density Lipoprotein Concentrations
Authors: Nikkilä Esko A , Hormila Pirkko 
Published: September 2013

In view of the high incidence of coronary heart disease in insulin-dependent diabetes, we determined cholesterol and triglyceride concentrations in serum and in three major lipoprotein fractions of 170 nonuremic middle-aged diabetic patients who had been treated with insulin for a minimum of 10 years. In addition, postheparin plasma lipoprotein lipase activity was measured in a subsample of the diabetic subjects. The diabetics had serum cholesterol and triglyceride concentrations similar to those of nondiabetic control subjects of the same age and sex. However, the concentration of high density lipoprotein (HDL)-cholesterol was significantly higher in both male and female diabetic patients than in respective controls (P &lt; 0.001). Male patients with poor diabetic control or with overweight had elevated triglyceride and very low density lipoprotein (VLDL)-triglyceride concentrations, whereas the patients with good diabetic control had significantly lower triglyceride and VLDL-triglyceride concentrations than did nondiabetic subjects. Overweight diabetic patients also had elevated serum cholesterol and LDL-cholesterol concentrations. The HDL-cholesterol of diabetic subjects, on the other hand, was not dependent on the degree of diabetic control or on the relative body weight. Diabetic patients had higher lipoprotein lipase activity in postheparin plasma than did normal subjects of corresponding age and sex. The HDL-cholesterol concentration showed a significant positive correlation with postheparin plasma lipoprotein lipase activity.
We conclude that the average serum lipid and lipoprotein pattern of insulin-treated chronic diabetic patients is not more. atherogenic than that of nondiabetic subjects of similar age and sex. On the contrary, the increase of HDL-cholesterol observed in the diabetic subjects should make them less liable to develop coronary heart disease. Thus, the excess cardiovascular disease that is associated with insulin-dependent diabetes must be accounted for by other factors.
Insulin-dependent Childhood Diabetes: Normal Viability of Cultured Fibroblasts
Authors: Rosenbloom Arlan L , Rosenbloom Edith K 
Published: September 2013

Cultured skin fibroblasts from clinically normal offspring of two parents with non-insulin-dependent diabetes have demonstrated premature senescence as a decreased ability of cells to establish colonies when inoculated at low density (plating efficiency). The present study tested the hypothesis that there is an inherent cellular defect affecting viability of diabetic cells in insulin-dependent diabetes. Four insulin-dependent patients, aged 12 to 19 years, included two with joint contracture, skin changes, and growth failure; one with thyroiditis and past history of nephrosis; and one with a family history of insulin dependency. Ten control subjects, aged 10 to 52 years, had negative family histories and normal oral glucose tolerance tests.
Number of cells per confluent dish correlated significantly with donor age (p &lt; 0.001) at 30 and 40 in-vitro generations. The patients' cells' mean confluent density did not differ from that of five age-matched controls. Plating efficiency correlated with donor age at 30 in-vitro generations (p &lt; 0.001); plating efficiency of cells from the youngsters with diabetes was virtually identical to that of control cells at 20, 30, and 40 generations.
In this small series of two subjects with in-vivo growth failure, one with associated autoimmune disease and another with familial insulin-dependent disease, cultured fibroblasts demonstrated normal viability and the hypothesis of a cellular growth defect was not confirmed.
Observations on the Value of Mass Indiscriminate Screening for Diabetes Mellitus Based on a Five-year Follow-up
Authors: Genuth Saul M , Houser Harold B , Carter James R , Merkatz Irwin R , Price J Waide , Schumacher O Peter , Wieland Ralph G 
Published: September 2013

Persons screened for diabetes in 1969 by a two-hour post-Giucoia capillary blood glucose determination (cutoff 140 mg./100 ml.) were retested in 1974. In matched positive/negative pairs, the relative risk for diabetes five years later was 22 times greater in the positive subjects. However, about half the 1969 positive subjects retested negative in 1974. Sixty per cent of these had had 1969 blood glucose concentrations less than 180 mg./100 ml. and 70 per cent had already failed to retest positive in 1969. In contrast, of the 1969 positive subjects who had evidence of diabetes in 1974, 60 per cent had 1969 blood glucose concentrations greater than 180 mg./ 100 ml. and 75 per cent had retested positive in 1969. Treatment status (diet versus medication) in 1974 of the 1969 positive subjects was related to the degree of hyperglycemie exhibited in 1969 and in 1974 as well as to the impregnation of the diagnosis into the patient by his physician.
We conclude that the misassignment (intentional or unintentional) of a diagnosis of diabetes mellitus to borderline hyperglycemie individuals occurs with sufficient frequency in indiscriminate mass screening programs to question their value. Efforts now expended in such programs should be directed to targeted populations to improve individual and public benefits.
Selective Calcification of Pancreatic Islets of Langerhans: An Unusual Association with Hypercalcemia and Diabetes Mellitus
Authors: Cotelingam James D , Hellstrom H Richard 
Published: September 2013

An unusual and extensive calcification of islets of Langerhans was found at autopsy in a man, 58 years old, who developed myeloma and, subsequently, hypercalcemia and diabetes. Although the islet cell calcification appears to be related to the hypercalcemia, the pathogenesis of the calcification is not clear, as primary metastatic calcification of pancreatic islets due to hypercalcemia does not occur. In support of this, a retrospective study of pancreatic tissue from 52 hypercalcemic patients with parathyroid adenoma and 34 patients with multiple myeloma, who frequently have hypercalcemia, did not reveal islet calcification.
The islet calcification is ascribed to primary islet cell degeneration and necrosis, with hypercalcemia playing an augmenting but crucial role. It is considered that the combination of islet degeneration and calcification resulted in the diabetic state.
The Immunohistopathology of Glomerular Antigens: III. Increased Mesangial Actomyosin in Experimental Diabetes in the Rat
Authors: Scheinman Jon I , Steffes Michael W , Brown David M , Michael Mauer S 
Published: September 2013

Antisera to rat smooth muscle actomyosin (AMY) and myosin localize in the rat glomerular mesangium. The width of mesangial staining for AMY is increased in rats diabetic for four months (p &lt; 0.01) and seven months (p &lt; 0.0005) compared with age-matched controls. Mesangial AMY staining of unilaterally nephrectomized control animals was moderately increased after seven months, whereas unilaterally nephrectomized diabetic rats had prominently increased AMY mesangial width at four months, when they were compared with intact diabetic animals (p &lt; 0.05).
Thus, a distinctive alteration that is found in human diabetic nephropathy also occurs in experimental (streptozotocin) diabetes in the rat. Further, this alteration appears to be accelerated by the changes in nephron hemodynamics resulting from unilateral nephrectomy. While the function of mesangial AMY is unknown, it may be related to intrarenal regulation of glomerular ultrafiltration, which appears to be altered in diabetic nephropathy in man.
Effects of Chronic Glucagon Excess on Hepatic Metabolism
Authors: Boden Guenther , Wilson Robert M , Owen Oliver E 
Published: September 2013

To investigate the effect of chronic hyperglucagonemia on hepatic metabolism, we have studied net splanchnic glucose and ketone body production rates in a patient with glucagonoma before and after complete tumor resection. Preoperatively, immunoreactive glucagon (IRG) concentration was high (1,800 pg. per milliliter) and the molar insulin/glucagon (I/G) ratio was low (0.4). Arterial free fatty acid (FFA) concentration (0.74 mM) and net splanchnic FFA uptake (0.27 mmole per minute) were normal. However, 48 per cent of the net splanchnic FFA uptake was utilized for net splanchnic ketone body production, which was four times (0.52 mmole per minute) greater than normal. Postoperatively IRG (40 to 150 pg. per milliliter) and the molar I/G ratio (&gt; 1.0) were both normal. Arterial FFA concentration and net splanchnic FFA uptake were unchanged (0.67 mM and 0.27 mmole per minute, respectively). However, only 19 per cent of the net splanchnic FFA uptake was utilized for net splanchnic ketone body production, which had declined to 0.19 mmole per minute. These data suggest that chronic hyperglucagonemia in this patient had a stimulating effect on ketogenesis.
Preoperatively, the net splanchnic glucose production rate was 0.56 mmole per minute and could be accounted for entirely by gluconeogenesis from lactate (83 per cent), pyruvate (9 per cent), glycerol (14 per cent), and alanine, glutamine, and glutamate (8 per cent). The abnormally large contribution of lactate to gluconeogenesis was an effect of inappropriately elevated lactate concentration (0.88 mM) and increased blood flow (2,400 ml. per minute). Postoperatively the net splanchnic glucose production rate was 0.67 mmole per minute, of which 51 per cent could be accounted for by gluconeogenesis. The data provide no evidence for an effect of chronic hyperglucagonemia on splanchnic glucose production. However, they do not exclude a small stimulating glucagon effect on gluconeogenesis from amino acids.
Equilibrium Binding Assay and Kinetic Characterization of Insulin Antibodies
Authors: Goldman José , Baldwin David , Pugh William , Rubenstein Arthur H 
Published: September 2013

A simple and precise equilibrium binding assay has been developed for the quantitation of circulating insulin antibodies. This procedure differs from previously reported methods in that (1) serum samples were deinsulinized in order to avoid endogenous insulin's interfering with the binding assay, (2) l25I-monoiodoinsulin was used to prevent artifacts resulting from variability in ligand binding due to excessive iodination, and (3) separation of free and bound insulin was accomplished by rapid precipitation of the hormone-antibody complexes without disturbing the binding equilibrium. This approach prevented dissociation and underestimation of the bound species.
In agreement with previous reports, two classes of antibody sites (high-affinity-low-capacity and low-affinity-high-capacity) were demonstrated in the sera of insulin-treated diabetic patients. No consistent differences existed in the association constants and/or binding capacities for insulins of bovine, porcine, and human origin, even though the immunogenic stimulus for antibody formation in these patients was treatment with commercial preparations of bovine and porcine insulins. Thus, higher affinities and/or binding capacities for human versus bovine and porcine insulins does not provide evidence for an autoimmune origin of insulin antibodies, as has been previously proposed. Significant differences in the antibody-binding capacities for all three species of insulin were found in individual serum samples, and underestimation of antibody titers may occur if only one species of the hormone is used.
Kinetic studies on the dissociation of the insulin-antibody complexes revealed two classes of dissociating sites, in agreement with the equilibrium binding data. The corresponding dissociation rate constants were large enough to implicate the release of insulin from the pool of antibody-bound hormone as a possible hypoglycemic mechanism in some diabetic patients.
Impaired Granulocyte Adherence: A Reversible Defect in Host Defense in Patients with Poorly Controlled Diabetes
Authors: Bagdade John D , Stewart Mary , Walters Elwanda 
Published: September 2013

When the ability of granulocytes from 10 poorly controlled diabetic patients with fasting hyperglycemia and no evidence of ketoacidosis (mean fasting glucose 293 ± 20 mg. per 100 ml.; mean ± S.E.M.) to adhere to a nylon fiber column was assessed, the number of adherent granulocytes from whole blood was only 53 ± 6 per cent of the values observed in controls. After antidiabetic treatment for one to two weeks and lowering of fasting glucose levels (mean 198 ± 29 mg. per 100 ml.), adherence improved significantly (p &lt;0.01) in the diabetics; however, their values were still subnormal (diabetic 74 per cent ± 8 of control; p &lt; 0.02). Adherence values before and after treatment correlated with the fasting glucose level (r = 0.88, p &lt;0.001).
These findings suggest that, in addition to previously reported abnormalities in migration and the ingestion and killing of bacteria, granulocyte adherence may also be impaired in poorly controlled diabetic patients. This functional abnormality correlates directly with the fasting glucose and is reversed by insulin treatment. A defect of this type may compromise the normal inflammatory response in some diabetics and impair their capacity to resist infection.
Characteristics of Human Erythrocyte Insulin Receptors
Authors: Gambhir Kanwal K , Archer Juanita A , Bradley Carole J 
Published: September 2013

Highly specific insulin receptors have been identified on human erythrocytes. A modification of the monocyte insulin radioreceptor technique permitted distinct separation of human erythrocytes with their bound insulin from the free insulin. When incubated with 80 pg. per milliliter of 125I-insulin (pH 8.0, 3.5 hours, 15 ° C.), erythrocytes from 17 normal volunteers specifically bound 10 per cent (± 1.450 S.D.) of the total 125I-insulin. Less than 15 per cent of the total 125I-insulin bound was nonspecific. Binding of 125I-insulin to human erythrocytes was dependent on pH and temperature. Less than 5 per cent of the insulin available to the plasma membrane was degraded. Both calcium and magnesium enhanced 125I-insulin binding by 100 per cent but had no synergistic effect when mixed in a 1:1 molar ratio.
Scatchard analysis of the binding data resulted in a curvilinear plot with characteristics typical of negative cooperative interactions between receptor sites and with an unoccupied site affinity constant of 0.1 × 108 M-1. Human erythrocytes have 2,000 insulin binding sites per erythrocyte with 14 sites per square micrometer of surface area. The readily available human erythrocyte, thus, has both specific insulin binding sites and binding characteristics similar to other human cell types. These studies have provided the basis for further clinical investigation of polypeptide hormone receptors on human erythrocytes.
Relation of Insulin Release to Cyclic AMP Content in Rat Pancreatic Islets Maintained in Tissue Culture
Authors: Rabinovitch Alexander , Cuendet Guy S , Sharp Geoffrey W G , Renold Albert E , Mintz Daniel H 
Published: September 2013

This study was designed to elucidate the role of adenosine 3′, 5′-monophosphate (cAMP) in the decreased glucose-induced insulin release observed in cultured pancreatic islets. Freshly coUagenase-isolated rat islets and islets that had been maintained in tissue culture medium for two to 140 hours (six days) were incubated for one hour with 3H-2-adenine, and insulin release and islet 3H-cAMP accumulation were measured in subsequent short-term (3 to 60 minutes) incubations.
There was a progressive decrease in the stimulatory effect of 20 mM glucose on insulin release in islets that had been cultured for 2, 4, and 20 hours, and, after 20 to 140 hours of culture, glucoseinduced insulin release was about one-third that in freshly isolated islets. Similarly, 20 mM glucose stimulated a threefold increase in 3H-cAMP content in fresh islets, but did not increase 3H-cAMP in islets cultured for four to 140 hours. Basal insulin release and islet 3H-cAMP levels were two- to threefold higher in islets cultured for 44 hours in 16.7 mM glucose rather than in 5.6 mM glucose. However, the sensitivity and capacity of glucose-induced insulin release were less in islets cultured in medium with either 5.6 or 16.7 mM glucose than in freshly isolated islets, and glucose did not further increase islet 3H-cAMP levels in the cultured islets. By contrast, 3-isobutyl-l-methylxanthine (IBMX, 1 mM) increased insulin release and 3H-cAMP content in both fresh and cultured islets. Glucagon (10 μM) increased insulin release and 3H-cAMP content in cultured islets better than in fresh islets; and glucagon (10 μM) plus IBMX (1 mM) increased insulin release and islet 3H-cAMP content similarly in fresh and cultured islets.
It is concluded that there is rapid and, apparently, selective loss in the short-term action of glucose to increase the cAMP content in islets maintained in vitro, and this may account for the impaired insulin-releasing action of glucose observed in cultured islets.
Stimulatory Effects of Prostaglandins E-l, E-2, and F-2-Alpha on Glucagon and Insulin Release In Vitro
Authors: Pek Sumer , Tai Tong-Yuan , Elster Alan 
Published: September 2013

The effects of prostaglandins (PG) E1, E2, and F2 upon the release of glucagon and insulin from the isolated perfused rat pancreas were investigated. In the presence of 5.6 mM glucose the release of both glucagon and insulin was stimulated by PGF2α at several concentrations ranging from 2.8 × 10−8 M to 3.6 × 10−6 M. Ten-minute perfusions of 1.4 × 10−6 M PGE1 or 2.8 × 10−7 M PGF2α evoked biphasic release of both islet hormones, and they augmented their biphasic release induced by 10 mM L-arginine. The addition of 5 mM fumarate, glutamate, and pyruvate permitted PGE2 to stimulate insulin release at a concentration as low as 1.1 × 10−9 M. The failure of 10−6 M oleic acid to elicit hormone release suggested that these effects of PGs were not nonspecific effects of long-chain fatty acids. In the absence of glucose, in response to 2.8 × 10−7 M PGE1 or PGE2 or PGF2α, the magnitudes of glucagon release were similar to or slightly greater than those seen with 5.6 mM D-glucose, but the release of insulin failed to occur. In the presence of 16.7 mM glucose, in response to 1.4 × 10−6 M PGE2 and 2.8 × 10−7 M PGF2α, the release of glucagon was blunted and that of insulin unchanged as compared with the secretory responses seen in the presence of 5.6 mM D-glucose.
These data indicate that administered PGs can stimulate acutely the release of glucagon and insulin at pharmacologic concentrations as well as at concentrations similar to those found in pancreatic tissues and effluent.
These observations are in keeping with the hypothesis that PGs of the E and F series may play a role in the regulation of secretion of glucagon and insulin.
Effects of Pancreatic Islet Transplantation on the Increased Urinary Albumin Excretion Rates in Intact and Uninephrectomized Rats with Diabetes Mellitus
Authors: Mauer S Michael , Brown David M , Matas Arthur J , Steffes Michael W 
Published: September 2013

The effects of reduced renal mass and of islet transplantation on urinary albumin excretion (UAE) rates in diabetic rats were examined. Increased UAE rates were noted two months after the induction of streptozotocin diabetes in 100-gm. inbred Lewis rats. Over the subsequent seven months, UAE rates remained constant in controls but were increasing in diabetic rats at the end of this time. Uninephrectomized nondiabetic rats had increasing UAE with time as compared with intact controls. Uninephrectomized diabetic rats had greater UAE than their respective controls, and the magnitude of this difference increased over the nine-month period of these studies. Uninephrectomized and intact rats, diabetic for seven months, were cured of the diabetic state by neonatal pancreatic tissue administered via the portal vein. Within one month of transplantation, UAE values decreased in these animals as compared with their pretransplant values and, within two months, were no longer different from values in their respective nondiabetic controls. In contrast, untreated uninephrectomized and intact diabetic rats increased their UAE over these same two months. At two months posttransplant, glomerular mesangial thickening was decreased in transplanted uninephrectomized and intact diabetic rats when compared with their respective untreated diabetic littermates.
Thus, the albuminuria of diabetes in rats is reversed by pancreatic islet transplantation. It is unclear whether this reversal is primarily due to improvement in functional or structural abnormalities in glomeruli of diabetic rats.