bluuebunny/crossref_metadata_2025_split huggingface dataset:
HLA-DRw Antigens in Mexican-American and Black-American Diabetic Patients
Authors: Zeidler Adina , Loon Jimmy , Frasier S Douglas , Kumar Dinesh , Penny Robert , Terasaki Paul 
Published: September 2013

HLA-A, -B, and -C antigens were studied in 67 Mexican-American and 38 black-American diabetic patients who had the onset of their disease before age 31 yr. Control populations consisted of 322 Mexican-American and 367 black-American subjects for HLA-A, -B, and -C antigens. In addition, HLA-DRw antigens were studied in 60 Mexican-American and 34 black-American diabetic patients. Control populations for HLA-DRw antigens consisted of 189 Mexican-American and 145 black-American subjects.
We found that juvenile-onset-diabetic patients of Mexican-American origin who had the onset of their disease before age 19 demonstrated a significant increase in HLA-DRw4. HLA-DRw4 was also significantly increased in black-American patients with juvenile-onset diabetes mellitus. HLA-DRw2 was not detected in any patient with juvenile-onset diabetes in either ethnic group. A significant association was found between HLA-B18 and HLA-DRw3 in Mexican-American juvenile-diabetic patients.
These findings, which are comparable to those in similar Caucasian patients, provide additional information to support the hypothesis that HLA-DRw antigens play a major role in determining the susceptibility to juvenile-onset diabetes mellitus.
Dissociation Between Plasma Triglyceride Concentration and Tissue Lipoprotein Lipase Deficiency in Insulin-deficient Rats
Authors: Chen Yii-Der I , Howard Julie , Huang Virginia , Kraemer Fredric B , Reaven Gerald M 
Published: September 2013

SUMMARY
Insulin deficiency was produced by streptozotocin in young (5–6 wk old) male rats, and measurements were made of plasma triglyceride and glucose concentrations and of lipoprotein lipase (LPL) activity of adipose tissue (epididymal) and muscle (gastrocne-mius and soleus). Rats with streptozotocin-induced diabetes underwent a significant reduction in adipose tissue LPL activity (both total and heparin releasable), but the fall in LPL activity in these rats bore little relationship to their rise in plasma triglyceride concentration. Furthermore, muscle LPL activity was essentially unchanged in diabetic rats. Qualitatively similar changes were observed when measurements were made at either 8 a.m. (after the normal evening access to food) or 2 p.m. (6 h after food withdrawal). It is concluded that the hypertriglyceridemia that occurs secondary to insulin deficiency is not a simple function of decreased tissue LPL activity.
Changes in Nerve Conduction Velocity After Six Weeks of Glucoregulation With Portable Insulin Infusion Pumps
Authors: Pietri Angel , Ehle Albert L , Raskin Philip 
Published: September 2013

SUMMARY
Near normal glucoregulation was maintained in 10 patients with insulin-dependent (type I) diabetes mellitus for 6 wk with preprogrammed continuous subcutaneous insulin infusion using a portable battery-powered infusion pump (CSII). This form of therapy resulted in a statistically significant increase in motor nerve conduction velocity in the median and peroneal nerves compared with baseline values. There was no significant change in the motor nerve conduction velocity in the ulnar nerve or in the sensory nerve conduction studies. No changes occurred in five additional patients studied in similar fashion while on a conventional insulin regimen. These results suggest that the prevention of sustained hyperglycemia with CSII could theoretically result in the prevention of diabetic neuropathy. However, only long-term studies of CSII will provide the information necessary to determine the clinical relevance of the findings.
Effects of Glucose and Amino Acids on the Biosynthesis of DNA and Insulin in Fetal Rat Islets Maintained in Tissue Culture
Authors: Swenne Ingemar , Bone Adrian J , Howell Simon L , Hellerström Claes 
Published: September 2013

Islet growth and insulin biosynthesis in fetal rat islets have been studied in a recently developed in vitro culture system. Collagenase-digested pancreases of 22-day-old rat fetuses were maintained for 5 days in culture medium RPMI 1640 (11.1 mM glucose) to allow degeneration of acinar tissue. Intact pure islets, composed of more than 90% B-cells, were then collected and subsequently treated for 3 days in culture with different concentrations of glucose and amino acids. Islets were then labeled for 24 h with 3H-thymidine (DNA synthesis) or for 2 h with 3H-phenylalanine (insulin/protein biosynthesis). The specificity of the incorporation of 3H-thymidine into B-cell DNA has been investigated and characterized by both Chromatographie and autoradiographic studies. Moreover, using a colchicine metaphase arrest technique, a relationship was demonstrated between incorporation of labeled thymidine and mitotic incidence in the B-cells.
Incorporation of 3H-thymidine was significantly higher in the fetal than in the adult islets following treatment in all the different concentrations of glucose and amino acids studied. In the presence of 10% fetal calf serum, however, there was no increase in DNA synthesis in the fetal islets in response to high concentrations of glucose or amino acids. In media containing 2.5% fetal calf serum, there was a significant increase in the rates of DNA synthesis after addition of high concentrations of either glucose or amino acids.
Fetal islets showed a marked insulin biosynthetic response to an acute glucose challenge. Both the basal and stimulated rates of insulin biosynthesis were increased after treatment in high concentrations of glucose but not after treatment with amino acids. The results suggest an important role of nutrients in the regulation of B-cell growth and insulin biosynthesis and also a dissociation between the regulatory mechanisms of these two processes.
Reversal of the Enhanced Somatostatin Release from the Isolated, Perfused Diabetic Rat Pancreas after the Amelioration of Diabetes by Whole Pancreas Transplantation
Authors: Kadowaki Seizo , Taminato Tomohiko , Chiba Tsutomu , Goto Yasuo , Nozawa Masumi , Seino Yutaka , Matsukura Shigeru , Fujita Takuo 
Published: September 2013

To investigate the pancreatic endocrine function in streptozotocin-diabetic rats before and after the whole pancreas was transplanted, pancreatic insulin, gluca-gon, and somatostatin content and release were measured.
Highly inbred Lewis male rats were divided into the following three groups: normal control rats; streptozo-tocin-induced-diabetic rats; and streptozotocin-diabetic rats transplanted with whole pancreas. Studies in vivo revealed normalization of elevated blood glucose and marked improvement of the impaired arginine-induced plasma insulin release by the transplantation of a healthy pancreas into the diabetic rats. Neither basal nor arginine-induced plasma glucagon levels in the diabetic rats were significantly different from the normal group, but significantly higher plasma glucagon levels were found in the transplanted rats. Studies in vitro using the isolated perfused rat pancreas revealed a significant increase of somatostatin release from the diabetic pancreas, with a marked reduction of insulin release and almost normal glucagon release. In the transplanted rats, on the other hand, arginine-induced somatostatin release from the host pancreas was reduced to normal without a significant change in insulin or glucagon release. In addition, the endocrine function of the graft remained normal in the transplanted rats.
Pancreatic somatostatin release, thus, appears to be affected by changes in circulating insulin, since pancreatic transplantation effectively corrects the circulating insulin level.
Body Weight, Skeletal Muscle Morphology, and Enzyme Activities in Relation to Fasting Serum Insulin Concentration and Glucose Tolerance in 48-year-old Men
Authors: Lithell H , Lindgärde F , Hellsing K , Lundqvist G , Nygaard E , Vessby B , Saltin B 
Published: September 2013

Tissue samples were taken from the gastrocnemius muscle of 26 randomly selected, glucose-tolerant, 48-yr-old men. Hexokinase, phosphorylase, lactate dehy-drogenase (LDH), succinate dehydrogenase, and lipo-protein lipase activity (LPLA), as well as the area per fiber type and capillary density, were determined.
Mean fiber area correlated positively with relative body weight (r = 0.53, P &lt; 0.01), but capillary density did not. The result is that, in cases of high body weight, each capillary supplies a larger muscle fiber area.
Serum insulin concentration in the fasting state correlated positively with body weight (r = 0.77, P &lt; 0.001) and with mean fiber area per capillary (r = 0.87; P &lt; 0.001). Only during the latter part of an oral glucose tolerance test (OGTT) did blood glucose concentrations correlate with relative body weight and mean fiber area per capillary (r = 0.42, r = 0.51, P &lt; 0.05). A stepwise multiple regression analysis showed that the different muscle morphology measurements could account for % of the variation in the fasting serum Insulin concentration, the fasting insulin/glucose ratio, and the blood glucose concentration at 120 min in the OGTT. Of the intracellular enzymes, only LDH (r = -0.71, P &lt; 0.001) correlated with the mean fiber area per capillary.
LPLA correlated with capillary density (r = 0.66, P &lt; 0.001), and, along with the muscle morphology measurements, could account for ¾ of the variation in serum triglyceride concentrations.
The results show that a large mean muscle fiber area/capillary ratio indicates a morphologic imbalance, which is related to both glucose tolerance and various degrees of insulin sensitivity.
Effect of Insulin Therapy on Insulin Resistance in Type II Diabetic Subjects: Evidence for Heterogeneity
Authors: Ginsberg Henry , Rayfield Elliot J 
Published: September 2013

Insulin resistance has been demonstrated previously in both glucose-intolerant and untreated type II diabetics. Although the former group had hyperinsulinemia in the fasting state and after an oral glucose load, the hyperglycemic type II subjects were relatively insulin deficient after carbohydrate ingestion. In an attempt to define the role that insulin deficiency might have played in the pathophysiology of insulin resistance in this latter group, we measured the steadystate plasma glucose level (SSPG) during a constant infusion of glucose (6 mg/kg/min) and insulin (80 mU/min) in 15 nonobese insulin-deficient type II diabetics before and after insulin replacement therapy. Hepatic glucose output (HGO) and plasma clearance of glucose (PCG) during these studies were also determined using an infusion of 3-3H-glucose.
Before insulin treatment, 13 of 15 subjects had SSPG levels above the range reported in normal subjects. Two type II patients appeared to be normally sensitive to insulin. Although all subjects were more sensitive to insulin after 1–8 wk of insulin therapy, they could be clearly divided into two groups. Thus, five patients were now normally sensitive to insulin (SSPG:75 ± 5.3 mg/dl) while 10 patients were still significantly resistant (SSPG: 227±11.3 mg/dl). HGO during the infusion studies was high in the resistant group pretreatment and did not change posttreatment (3.54 ± 0.32 vs. 3.14 ± 0.78 mg/kg/min). HGO was lower before insulin therapy and decreased by &gt; 50% after therapy in the sensitive group (1.93 ± 0.07 vs. 0.71 ± 0.32 mg/kg/min). PCG determinations revealed a similar pattern of response. Retrospective analysis of the two groups revealed no significant differences in their baseline characteristics. Fasting plasma glucose and hemoglobin A1c levels also did not differ between the two groups before or after insulin therapy.
These results indicate that heterogeneity exists among subjects with type II diabetes mellitus. One-third of the subjects studied appear to have only insulin deficiency as the basis of their diabetes, while two-thirds seem to have an underlying resistance to insulin that is not corrected by insulin therapy.
Effect of the Membrane Lipid Environment on the Properties of Insulin Receptors
Authors: Ginsberg Barry H , Brown Thomas J , Simon Ido , Spector Arthur A 
Published: September 2013

We have altered the fatty acid composition of the Friend erythroleukemia cells and studied the effect on the binding parameters of the insulin receptor. Cells were grown for about five generations in media enriched with oleate (a monounsaturated fatty acid) or linoleate (a polyunsaturated fatty acid). The microsomal phospholipids normally contained about 40% saturated, 40% monounsaturated, and 20% polyunsaturated fatty acids. In cells grown with oleate, monounsaturates rose to 63% and in cells grown with linoleate, the polyunsaturated component rose to 52%. Fluidity determination by electron spin resonance similarly indicated that the membranes of cells grown in linoleic acid were more fluid than those grown in oleic. Control cells demonstrated the least membrane fluidity.
The cells enriched in unsaturated fatty acids had an increased number of insulin receptors and decreased receptor affinity, but the exact interpretation of the change was dependent on the method of data analysis. When analyzed assuming negative cooperativity among a single class of receptors, there was an increase in receptor number from 23,000/cell in the control cells to 39,000/cell in the oleate-enriched and to 81,000/cell in the linoleate-enriched cells. These changes were accompanied by reciprocal decreases in the affinity of both the unoccupied form of the receptor (Ke) and the occupied form of the receptor (Kf). When analyzed assuming two independent classes of sites, there was no major change in the number or affinity of the high affinity receptors (6000–8000/cell). There was, however, a marked increase in the number of low affinity receptors from 15,000/cell in the control cells to 32,000/cell in the oleate-enriched and 74,000/cell in the linoleate-enriched cells. This increase in receptor concentration was again accompanied by a reciprocal decrease in the affinity of the low affinity receptor.
These studies thus demonstrate a relationship between the cellular fatty acid composition and the properties of insulin receptors. The observed changes could be due to alterations in the quaternary structure Of the receptor.
Nonenzymatic Glycosylation of Serum and Plasma Proteins
Authors: Kennedy Laurence , Mehl Thomas D , Elder Elizabeth , Varghese Matthew , Merimee Thomas J 
Published: September 2013

Albumin and other serum and plasma proteins may be nonenzymatically glycosylated in vitro and in vivo. Chromatographie and colorimetrie measurement of these nonenzymatically glycosylated proteins shows that levels are approximately two to three times higher in diabetic than nondiabetic subjects. In diabetic patients levels appear to reflect glycemia in the preceding several days and correlate with other established parameters of glycemia such as fasting serum glucose, mean of several capillary blood glucose measurements, and glycosylated hemoglobin. Because serum and plasma proteins have shorter half-lives than hemoglobin, nonenzymatically glycosylated proteins are altered more rapidly than glycosylated hemoglobin in response to prolonged decreases or increases in blood glucose levels.
Acetylsalicylic acid significantly inhibits in vitro glycosylation of albumin and other serum proteins incubated for up to 7 days in glucose. It is not known whether such inhibition occurs in vivo.
Glycosylation of albumin appears to reduce its solubility, and glycosylation of low-density lipoprotein may increase its catabolism. Whether nonenzymatic glycosylation of other serum proteins alters their functions or may contribute to some of the long-term complications of diabetes is unknown at present.
Expression of HLA-DR Antigens in Human Fetal Pancreas Tissue
Authors: Danilovs John A , Hofman Florence M , Taylor Clive R , Brown Josiah 
Published: September 2013

The expression of HLA-DR antigens in human fetal pancreas tissue was studied using four independently derived monoclonal antibodies recognizing nonpolymorphic HLA-DR antigens. Immunoperoxidase staining of frozen sections revealed numerous DR-antigenpositive cells. Two major cell types could be distinguished. Large, strongly DR-positive cells with dendritic morphology were distributed throughout the pancreatic parenchyma and interstitial connective tissue. Dual staining of DR antigens and insulin using a two-color immunoperoxidase technique clearly showed that some of these DR-positive dendritic cells were located within and in close association with insulin-producing islets.
Also observed as a regular feature of fetal pancreas tissue sections were large clusters of DR-positive cells with lymphoid morphology. Positive staining of many cells within these clusters with monoclonal antibodies against T-cell marker (Leu-1) and T-cell subset markers (Leu-2 and -3) supported their classification as lymphoid cells. In contrast, no positive staining with anti-T-cell antibodies was observed outside of lymphoid cell clusters, confirming the distinction between these cells and the DR-positive cells distributed throughout the pancreas. The presence of other DR-bearing cell types in fetal pancreas could not be excluded, but most endothelial cells appeared to be DR-negative.
The demonstration of numerous DR-bearing cells associated with fetal pancreas tissue may require that we alter our views on DR-antigen ontogeny and develop new strategies for fetal pancreas transplantation.
Skin Collagen Metabolism in the Streptozotocin-induced Diabetic Rat: Enhanced Catabolism of Collagen Formed Both Before and During the Diabetic State
Authors: Schneir Michael , Ramamurthy Nangavaram , Golub Lorne 
Published: September 2013

Collagen catabolism has been measured in skins of streptozotocin-induced diabetic rats. For measuring catabolism of collagen synthesized de novo during the diabetic state, we measured the amounts of [3H]hydroxyproline-containing degradation products in skins of diabetic rats, killed 4 h after [3H]proline injection (protocol 1); degradation products were isolated in TCA-soluble fractions of skin homogenates. For measuring catabolism of collagen preexisting before the induction of the diabetic state, we measured the 21-day loss of [3H]hydroxyproline (and hydroxyproline) in entire skins of rats that were streptozotocin-treated after [3H]proline injection (protocol 2).
A 2.5-fold increase in the relative amounts of [3H]hydroxyproline-containing degradation products was measured in the TCA-soluble fractions of skins from diabetic rats (protocol 1). These degradation products had a low molecular weight (as evident from their diffusibility), and they were derived from recently synthesized collagen, possibly procollagen (as evident from their high [3H]hydroxyproline specific activity). Furthermore, they were not derived from the degradation of [3H]hydroxyproline-labeled collagen present before induction of the diabetic state (protocol 2). Evidence for this conclusion is as follows: the amounts of [3H]hydroxyproline-containing degradation products in skins of diabetic rats were not greater than that in skins of control rats, despite a 50% resorption of collagen in skins of diabetic rats.
Overall, the catabolism of collagen formed de novo during the diabetic state was distinguished from the catabolism of collagen formed before, and both catabolic processes were enhanced in rat skins of streptozotocin-induced diabetic rats.
Virus-Induced Diabetes Mellitus: Glucose Abnormalities Produced in Mice by the Six Members of the Coxsackie B Virus Group
Authors: Toniolo Antonio , Onodera Takashi , Jordan George , Yoon Ji-Won , Notkins Abner Louis 
Published: September 2013

SUMMARY
The capacity of Coxsackie B viruses (CBVs) to produce diabetes in mice was studied before and after passage in various cell types. CBVs that had been passaged in monkey kidney cells or in mouse embryo fibroblasts failed to produce abnormal glucose tolerance tests, whereas virus passaged five or more times in the pancreata of mice or in beta-cell cultures p oduced transient abnormal glucose tolerance tests. Immunofluorescence and histologic studies revealed that passage of CBVs in cultured beta-cells changed the tropism of these viruses from the acinar pancreas to the islets of Langerhans. Although all six CBV serotypes that had been passaged in beta-cell cultures behaved very similarly, substantial variation was observed with the different virus passages and in some experiments, beta-cell damage and the glucose abnormalities were minimal. From these and other experiments, we conclude that the six members of the CBV group have the potential for infecting and damaging pancreatic beta-cells in mice.
Insulin, Glucagon, and Somatostatin Receptors on Cultured Cells and Clones from Rat Islet Cell Tumor
Authors: Bhathena Sam J , Oie Herbert K , Gazdar Adi F , Voyles Nancy R , Wilkins Samuel D , Recant Lillian 
Published: September 2013

SUMMARY
Cells grown in culture from rat islet cell tumor (parent cells) and clones obtained from them were used in this study. Parent cells secreted primarily insulin and somatostatin with very small quantities of glucagon. The clones, based on hormone content and secretion, were divided into three phenotypic groups: insulin secreting, somatostatin secreting, and nonsecreting clones. Specific receptors for insulin, glucagon, and somatostatin were demonstrated on parent cells and clones. Parent cells bound 4.12 ± 0.46% insulin, 2.11 ± 0.29% glucagon, and 2.49 ± 1.24% somatostatin per 2 × 106 cells. Characteristic hormone binding patterns were observed in insulin secreting versus somatostatin secreting clones. Insulin secreting clones bound less insulin than somatostatin and other noninsulin- secreting clones (P &lt; 0.02). In contrast, somatostatin secreting clones bound more somatostatin than non-somatostatin-secreting clones (P &lt; 0.05). Somatostatin-secreting clones had a significantly greater number of receptors for all three hormones. The difficulties involved in the interpretation of the quantitative aspects of binding in the presence of continued hormone secretion are discussed. Nonetheless, the presence of receptors on the cells for hormones secreted by the same cells strongly suggests autoregulation. The apparent low affinity of some of these receptors and the presence of receptors for all three islet cell hormones on all islet cells supports the likelihood of paracrine controls.