bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of Improvement in Glucose Metabolism After Chronic Glyburide Therapy
Authors: Simonson Donald C , Ferrannini Eleuterio , Bevilacqua Stefano , Smith Douglas , Barrett Eugene , Carlson Rodney , DeFronzo Ralph A 
Published: September 2013

The effect of glyburide on glucose metabolism was examined in 10 non-insulin-dependent diabetic subjects (NIDDM) and 7 young, control subjects. After 3 mo of glyburide treatment in NIDDM, fasting plasma glucose declined from 198 to 141 mg/dl (P &lt; 0.01) without change in fasting insulin levels. Basal hepatic glucose production (HGP) was slightly elevated in NIDDM versus controls (2.35 versus 2.18 mg/kg · min, P = NS) and was positively correlated with the fasting glucose concentration (r = 0.93, P &lt; 0.001). With chronic glyburide therapy, HGP declined to 1.72 mg/kg · min (P &lt; 0.01 versus preglyburide) and remained highly correlated with the fasting glucose concentration (r = 0.85, P &lt; 0.005). Basal glucose clearance in NIDDM was reduced by 48% compared with age-matched controls (1.22 versus 2.32 ml/kg · min, P &lt; 0.001) and was unchanged after 3 mo of glyburide. Thus, the most important factor responsible for the decline in fasting plasma glucose concentration was an inhibition of hepatic glucose output. The decrease in basal hepatic glucose production and fasting plasma glucose concentration occurred without any change in fasting plasma insulin or C-peptide concentration.
Insulin-mediated glucose metabolism (insulin clamp technique) was reduced by 55% in NIDDM (2.91 versus 6.39 mg/kg · min, P &lt; 0.001). After glyburide, insulin-mediated glucose metabolism increased by 26% to 3.67 mg/kg · min (P &lt; 0.01). This increase in tissue sensitivity to insulin was unassociated with any change in insulin binding to monocytes. Beta cell secretion of insulin (hyperglycemie clamp technique) was markedly impaired in NIDDM (mean plasma insulin response: 24 versus 54 μU/ml, P &lt; 0.001). After glyburide, the plasma insulin response increased to 36 μU/ ml (P &lt; 0.01). These results indicate that improved glucose tolerance in NIDDM after glyburide results from both enhanced tissue sensitivity to insulin and increased insulin secretion.
Glyburide administration to young, healthy, control subjects also increased insulin-mediated glucose metabolism (from 6.45 to 7.61 mg/kg · min, P &lt; 0.05) without any change in insulin binding to monocytes. Insulin secretion, however, was unaltered. Thus, the primary mechanism responsible for the improvement in glucose metabolism in young controls was enhanced tissue sensitivity tO insulin.
Influence of Physical Training on Formation of Muscle Capillaries in Type I Diabetes
Authors: Wallberg-Henriksson Harriet , Gunnarsson Rolf , Henriksson Jan , Östman Jan , Wahren John 
Published: September 2013

The effects of physical training on skeletal muscle morphology and enzyme activities were compared in 10 male, type I diabetic subjects and 10 healthy, male, control subjects. The training program consisted of running for 45 min, three times per week for 8 wk. Muscle biopsies were obtained before and after the training period from the lateral portion of the gastrocnemius muscle. Pretraining maximal oxygen uptake was similar in the two groups (diabetic subjects 42 ± 1 versus control subjects 43 ± 2 ml × kg−1 × min−1), and the training resulted in an identical increase (+ 13%, P &lt; 0.01). Muscle capillarization (number of capillaries per muscle fiber) increased on the average in the control group (+ 14 ± 4%, P &lt; 0.01), but was unchanged in the diabetic group (0 ± 4%). Capillary density, expressed as number of capillaries per unit muscle cross sectional area, also increased on the average in controls (8 ± 4%, P &lt; 0.05) but failed to do so in the diabetic patients (–8 ± 6%, NS). The activities of the mitochondrial enzymes citrate synthase (+ 26–27%, P &lt; 0.01–0.05) and succinate dehydrogenase (+ 24–25%, P &lt; 0.05) increased significantly and similarly in the two groups, whereas training did not result in significant changes in the activities of the glycolytic enzymes 6-phosphofructokinase and glyceraldehyde-phosphate dehydrogenase. Glycemie control in the diabetic group did not improve with the training, as evaluated from hemoglobin A1 and home-monitored blood glucose.
The findings suggest that, compared with controls, the ability to form new skeletal muscle capillaries in response to physical training may be deficient in patients with type I diabetes mellitus of long standing, while the increase in mitochondrial enzyme activities is normal. A deficient formation of new capillaries may be an expression of the microangiopathy of this disorder.
Effects of Prior High-Intensity Exercise on Glucose Metabolism in Normal and Insulin-resistant Men
Authors: Devlin J T , Horton E S 
Published: September 2013

The effects of prior high-intensity cycle exercise (85% VO2 max) to muscular exhaustion on basal and insulinstimulated glucose metabolism were studied in obese, insulin-resistant, and normal subjects. Six obese (30.4% fat) and six lean (14.5% fat) adult males underwent two separate, two-level hyperinsulinemic-euglycemic clamp studies (100-min infusions at 40 and 400 mU/m2/min), with and without exercise 12 h earlier. Carbohydrate oxidation was estimated by indirect calorimetry using a ventilated hood system, and endogenous glucose production by D-(3-3H)-glucose infusion. Glycogen content and glycogen synthase activity (GS %l) were measured in vastus lateralis muscle biopsies before and at the end of each insulin clamp procedure.
After exercise, the obese and lean subjects had comparably low muscle glycogen concentrations (0.10 versus 0.08 mg/g protein, respectively), and equal activation of muscle GS activity (54.4 versus 45.3 GS %l, respectively). In the obese subjects, insulin-stimulated glucose disposal was increased significantly, but not totally corrected to normal. In both groups there was a comparable increase in nonoxidative glucose disposal (NOGD), whereas glucose oxidation was decreased and lipid oxidation was increased. Thus, the major effect of prior exercise was to increase insulin-stimulated glucose disposal in the obese subjects and to alter the pathways of glucose metabolism to favor NOGD and decrease glucose oxidation.
No correlation was found between the exercise-induced increase in GS %l and NOGD, except in the normal subjects during maximal insulin stimulation. Thus, glycogen synthase activity does not appear to be ratelimiting fpr NOGD at physiologic insulin concentrations. Our findings suggest that a single bout of glycogendepleting exercise can increase glucose disposal for at least 12–14 h in obese subjects with insulin resistance.
Effects of Gestational Hyperglycemia on Glucose Metabolism and Its Hormonal Control in the Fasted, Newborn Rat During the Early Postnatal Period
Authors: Nurjhan N , Ktorza A , Ferre P , Girard J R , Picon L 
Published: September 2013

To evaluate the effects of gestational hyperglycemia on glucose metabolism and its regulation in the fasted rat during the early postnatal period, unrestrained rats were continuously infused with glucose during the last week of pregnancy. Control rats were infused with distilled water. Newborns were studied during the first six postnatal hours.
At birth, newborns from glucose-infused rats, compared with controls, showed higher plasma glucose levels, increased plasma insulin, and lower plasma glucagon and catecholamine concentrations.
Between birth and 2 h postpartum, newborn rats from both groups exhibited a marked hypoglycemia, which was, however, more severe in newborns from glucose-infused rats (15 mg/dl) than in controls (26 mg/dl). During the first four postnatal hours, plasma insulin concentration remained higher, while plasma glucagon and catecholamine concentrations remained lower in newborns from hyperglycemic rats. At 6 h, the glycemia reached normal values and the concentrations of the different hormones were similar in controls and newborns from glucose-infused mothers.
Concurrently, in the newborns from glucose-infused rats, hepatic glucose production was altered, as they were unable to mobilize liver glycogen stores during the six postnatal hours. Despite slightly delayed phosphoenolpyruvate carboxykinase induction, the rate of gluconeogenesis from 10 mmol/L lactate estimated on isolated hepatocytes was higher in newborns from hyperglycemic mothers than in controls.
These results show that gestational hyperglycemia compromises the metabolic and hormonal adaptation of the newborn rat to early extrauterine life; the striking feature of these neonates is the absence of mobilization of liver glycogen stores, which can probably be explained by fetal and neonatal hyperinsulinism associated with the defect of counterregulatory hormones.
Insulin Clearance Contributes to the Variability of Nocturnal Insulin Requirement in Insulin-dependent Diabetes Mellitus
Authors: Dux Shlomo , White Neil H , Skor Donald A , Santiago Julio V 
Published: September 2013

We have previously described, in insulin-dependent diabetic subjects (IDDM), a small, but significant, increase in the insulin clearance rate (ICR) during 0600–0800 h as compared with 0100–0300 h. To determine whether this increase was also seen at more physiologic levels of insulin replacement, we calculated ICR during euglycemic clamp studies in 13 patients with IDDM with a constant infusion of insulin at 20 mU/min/ m2 and during insulin replacement from the Biostator GCIIS without exogenous glucose.
During the euglycemic clamp study with constant insulin infusion at 20 mU/min/m2, the ICR was 16% higher at 0600–0800 h than at 0100–0300 h (264 ± 50 ml/min/m2 versus 228 ± 51 ml/min/m2; P &lt; 0.005). During insulin replacement by the Biostator, the mean insulin infusion rate increased by 92 ± 27% (7.5 ±1.1 to 13.5 ±1.2 mU/min/m2; P &lt; 0.001) and ICR increased by 123 ± 30% (130 ± 24 to 268 ± 51 ml/min/m2; P &lt; 0.01) during the prebreakfast period when compared with 0100–0300 h. There was a highly significant correlation (r = 0.97) between the increment in insulin infusion rate and the increment in ICR.
Measurement of insulin concentration in saline solutions, delivered by the Biostator at a same rate and under similar conditions to those in this study, showed that insulin delivery was stable for the 8-h period of this study.
We conclude that, at levels of insulin replacement that maintain blood glucose between 90 and 100 mg/dl, variation in the ICR is an important contributor to the “dawn phenomenon” of increasing early morning blood glucose concentration and insulin requirements in diabetic subjects.
Acanthosis nigricans in Obese Women with Hyperandrogenism: Characterization of an Insulin-Resistant State Distinct from the Type A and B Syndromes
Authors: Flier Jeffrey S , Eastman Richard C , Minaker Kenneth L , Matteson Doreen , Rowe John W 
Published: September 2013

Acanthosis nigricans and hyperandrogenism are commonly found in patients with extreme target cell resistance to insulin, as in the type A and B syndromes of insulin resistance. However, the significance of concurrent acanthosis nigricans and hyperandrogenism in other clinical settings is not clear. We observed acanthosis nigricans to be present in 5% (15 of 300) of patients being evaluated for hyperandrogenism, and carried out studies of insulin binding and action in a group (7) of these women. Although none were diabetic, all were insulin resistant as assessed by hyperinsulinemia when fasting and after oral glucose administration. All patients were obese (mean IBW, 169%). However, when matched to hyperandrogenized women of similar body weight, patients with acanthosis nigricans were clearly more hyperinsulinemic. Insulin binding to monocytes and red cells was decreased in patients with acanthosis, and the extent of decrease was predicted by the fasting insulin level. There was also marked resistance to exogenous insulin during euglycemic insulin clamp studies in the two patients so tested. Anti-insulin receptor antibodies were not detectable, ruling out the type B syndrome. Unlike the type A syndrome, insulin binding to monocytes of these patients increased after acute (2/2) and chronic (1/1) caloric restriction. In the latter patient, acanthosi nigricans remitted as insulin resistance and the insulin binding defect improved.
We conclude that acanthosis nigricans is present in as many as 5% of women with clinically significant hyperandrogenism. These women, although not diabetic, have fairly marked insulin resistance. Despite a number of clinical similarities to patients with the type A and B syndromes, the insulin resistance of these women seems more likely to be a consequence of their obesity, and caloric restriction would appear to be the most appropriate therapy. The basis for apparent interrelationships between insulin, androgens, and acanthosis nigricans in these and other patients is discussed.
Observations on Control of Glycemia with Conventional Insulin Therapy or Continuous Subcutaneous Insulin Infusion
Authors: Tamborlane William V , Champion Malcolm C , Rizza Robert A , Service F John , Bergenstal Richard M ,   The Kroc Collaborative Study Group
Published: September 2013

Determination of glycemic differences between groups treated with continuous subcutaneous insulin infusion (CSII) or conventional insulin therapy (CIT) was central to the major objective of the study. Assessment of glycemia was based on (1) 24-h inhospital profiles of plasma glucose; (2) pre- and postprandial and bedtime (seven time points) diurnal profiles performed monthly on outpatient samples; and (3) glycosylated hemoglobin (HbA1) measured bimonthly at each center. The correlation between plasma glucose determinations in the central laboratory and in local laboratories was 0.988. Significance of differences between treatments was by analysis of variance and least-squares regression.
At baseline, mean inhospital plasma glucose and HbA1, concentrations and insulin dosages were identical in the groups randomized to CSII or CIT. A prompt decrement of indices of glycemic control during CSII was observed such that mean decrements sustained over the 8-mo treatment period in home and in hospital plasma glucose profiles and HbA1 relative to values obtained during CIT (P &lt; 0.0001). The likelihood of CSII-treated patients achieving glycemic indices within the normal range was increased. The standardization of the mean and the M-value calculated from inhospital glucose profiles during CSII and CIT at 4 and 8 mo indicated that there was less plasma glucose fluctuation during CSII.
The method of pooling standardized local HbA1 measurements from the six centers appeared to be an adequate substitute for centrally performed HbA1 determinations. Advantages of inhospital plasma glucose measurements in terms of accuracy and ability to obtain nocturnal samples contrasted with the likelihood of increased realism and superior correlation with HbA1, in home-obtained samples. We have shown in insulin-dependent diabetic patients that prerandomization levels of glycemia were unchanged during CIT, and during CSII a significant decrease in glycemia was established and sustained. The primary aim of the study has thus been achieved.
Albumin Permeation of New Vessels Is Increased in Diabetic Rats
Authors: Kilzer Paul , Chang Kathy , Marvel Joyce , Rowold Edwin , Jaudes Phyllis , Ullensvang Suzanne , Kilo Charles , Williamson Joseph R 
Published: September 2013

125I-bovine serum albumin (BSA) permeation of the vasculature of 3-wk-old granulation tissue (induced by subcutaneous implantation of polyester fabric) formed in the diabetic milieu was assessed in female BB/W, spontaneously diabetic rats and in male, Sprague-Dawley rats with streptozocin-induced diabetes as well as in corresponding nondiabetic controls. Albumin permeation of new granulation tissue vessels was markedly increased in both groups of diabetic animals relative to that of nondiabetic controls, while albumin permeation of vessels in most other tissues did not differ for controls and diabetics. These observations indicate that the functional integrity of new vessels formed in the diabetic milieu is impaired: (1) to a greater extent than that of older vessels formed before induction of diabetes and (2) relative to new vessels in nondiabetics.
The implication of these observations is that molecular constituents of vessels synthesized in the diabetic milieu are quantitatively and/or qualitatively abnormal and/or their incorporation into vessels is defective.
Bone Calcification and Calcium Homeostasis in Rats with Non-insulin-dependent Diabetes Induced by Streptozocin
Authors: Levy Joseph , Teitelbaum Steven L , Gavin James R , Fausto Aurora , Kurose Hirofumi , Avioli Louis V 
Published: September 2013

The effect of mild, non-insulin-dependent diabetes (NIDDM) on bone calcification and calcium (Ca) homeostasis was studied in growing rats (males and females). The diabetic state was characterized by mild insulin deficiency, plasma levels being 73% of controls, and mild hyperglycemia, with nonfasting plasma glucose levels of 1.5 times normal. There was no difference in plasma levels of Ca, phosphate (Pi), magnesium (Mg), alkaline phosphatase, immunoreactive parathyroid hormone (iPTH), calcitonin, 25-(OH)vitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OHrsqb;2D), and 24,25-dihydroxyvitamin D (24,25[OH]2D) between the NIDDM rats and their controls of either sex. Metabolic Ca and Pi balance studies revealed that the experimental animals of both sexes were in positive Ca and Pi balance similar to that of their controls. Histologic studies of the kidney and intestinal slices from the experimental group were normal.
Ca and Pi bone content calculated per gram bone ash of the femur, mandible, and second and fourth caudal vertebrae, and the organic content in the bones of the NIDDM animals showed no difference from their controls. Femur bone density and tibial epiphyseal growth plate width and morphology were similar histologically in the experimental and control rats. No decreased osteoid content in the tibial bone was found in the diabetic rats compared with controls.
Physiologic sex differences, consisting of lower plasma Pi, higher plasma calcitonin levels, increased ratio of femur dry bone weight to total body weight, and increased percentage of mineralized and total bone volume at the tibial metaphysis seen in female compared with male control rats were also seen in the diabetic animals.
The data reveal that, in states of mild insulin deficiency in the rat, the factors that regulate mineral metabolism are functioning normally and bone mineralization proceeds without alterations. In addition, physiologic sex differences are preserved. There is no indication for bone loss under these conditions.
Lack of Association of the Polymorphic Locus in the 5'-Flanking Region of the Human Insulin Gene and Diabetes in American Blacks
Authors: Elbein Steven , Rotwein Peter , Permutt M Alan , Bell Graeme I , Sanz Nancy , Karam John H 
Published: September 2013

A polymorphic region 5' to the human insulin gene has been associated with diabetes in earlier studies. This polymorphic region is composed of tandem repeats that fall into 3 general size classes, designated class 1 (600 base pairs), class 2 (1300 base pairs), and class 3 (2500 base pairs). Frequencies of these classes of alleles vary among racial groups. American Blacks have been underrepresented in published studies of insulin gene polymorphism and diabetes.
We undertook a cooperative study between two centers (San Francisco and St. Louis) to determine genotypes at the insulin locus in 313 unrelated American Blacks (132 nondiabetic, 27 with IDDM, and 154 with NIDDM). In both centers, nondiabetic individuals were younger and leaner than NIDOM patients. Allelic and genotypic frequencies at the insulin locus were not different between the two centers. Class 1 alleles represented 60% of all alleles, class 2 alleles 11%, and class 3 29%. No class of insulin allele was associated with NIDDM in this study. Subdivision of the study population by obesity, family history, or age at diagnosis failed to detect a subgroup for which the insulin allele was associated with NIDDM. Only 27 IDDM individuals were studied, and no significant association of class 1 alleles with this group was noted. However, examination of more IDDM individuals is required before a definitive statement can be made.
Fasting serum triglyceride levels were determined retrospectively in 50 NIDDM individuals. No differences in triglyceride levels among genotypes were noted. The frequency of class 3 alleles in 13 hypertriglyceridemic NIDDM subjects was not different from that of the whole group.
Thus, in American Blacks there is no association of class 3 alleles with NIDDM. Studies using this polymorphic marker in linkage analysis of appropriate families may be more successful in defining a role for the insulin gene in diabetes.
Complement and HLA: Further Definition of High-Risk Haplotypes in Insulin-dependent Diabetes
Authors: Rich S , O'neill G , Dalmasso A P , Nerl C , Barbosa J 
Published: September 2013

The families of 41 probands with type I (insulin-dependent) diabetes mellitus (IDDM) were typed for HLAA, HLA-B, and HLA-DR antigens in addition to the complement polymorphisms C2, C4A, C4B, and Bf. All of these loci are encoded on the short arm of human chromosome 6 in a narrow region. Alleles at HLA-B (8, 15, 18, and 40), HLA-DR (3 and 4), and Bf (F1) have been associated with increased relative risk (RR) for IDDM, while HLA-B7 and HLA-DR2 have been associated with decreased RR for IDDM. This study confirms those significant risks in addition to confirming increased risk for the null (silent) allele for C4A (C4AQ0) and a rare C4B variant (C4B2.9). The significantly associated antigens (alleles) and risks were: HLA-B8 (RR = 3.1), HLA-DR3 (RR = 5.2), HLA-DR4 (RR = 4.3), and BfF1 (RR = 7.1), in addition to C4AQ0 (RR = 2.8) and C4B2.9 (RR = 12.6). Significantly low risk was associated only with HLA-DR2 (RR = 0.1).
In a recent study, we defined five high-risk haplotypes that were determined solely by HLA-B, Bf, and HLA-DR (B8-BfS-DR3, B8-BfS-DR4, B15-BfS-DR4, B18-BfF1-DR3, and B40-BfS-DR4). By inclusion of information from the complement polymorphism, we have defined in greater detail three of these five high-risk haplotypes. One previously identified haplotype (B40-BfS-DR4) showed no complement clustering, while the rare high-risk haplotype (B8-BfS-DR4) was seen only once in this smaller sample. Information at the HLA-A locus was deemed important only in the definition of the B8-BfS-DR3 extended high-risk haplotype. Three haplotypes that exhibited significantly increased risks with complement inclusion were B8-BfS-C2C-C4AQ0-C4B1-DR3 (RR = 2.4), B15-BfS-C2C-C4A3-C4B2.9-DR4 (RR = 10.2), and B18-BfF1-C2C-C4A3-C4BQ0-DR3 (RR = 10.6). Of possibly major significance, it was shown that all probands carried at least one high-risk antigen or allele.