bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dichloroacetate—Its In Vivo Effects on Carbohydrate Metabolism in the Conscious Dog
Authors: Diamond Michael P , Rollings Robert C , Erlendson Lee , Williams Phillip E , Lacy William W , Rabin David , Cherrington Alan D 
Published: September 2013

The effects of sodium dichloroacetate (DCA) on carbohydrate metabolism in conscious, 48-h-fasted dogs were examined using the hepatic A-V difference technique and a double isotope infusion technique (3H-glu-cose to measure glucose production and 14C-alanine to assess gluconeogenesis). DCA infusion (0.4 mg/kg-min) resulted in an 82 ± 1% fall in the arterial plasma alanine level and a 53 ± 8% fall in the arterial whole blood lactate level. Hepatic uptake of alanine and lactate fell 67 ± 5% and 59 ± 15%, respectively, although the fractional extraction of these intermediates was not altered. DCA decreased the conversion of circulating alanine and lactate to glucose but by only 41 ± 7%, suggesting that a slight increase in the efficiency of the intrahepatic gluconeogenic process took place. This may be explained by the decrease in the plasma insulin level (39 ± 9%) that occurred in the presence of an unchanged plasma glucagon concentration. Despite the substantial fall in the levels of gluconeogenic precursors in blood and the considerable decrease in their rate of conversion to glucose, the overall rates of glucose production and the blood glucose concentration were not altered by DCA.
These data indicate that the alanine and lactate supplied by the periphery after a 48 h fast in the dog are not essential for the acute maintenance of glucose production or euglycemia. They suggest, further, that a compensatory increase in glucose production can occur by drawing on an alternate intrahepatic carbon source, the nature of which and signal for which remain unclear.
Generalized Diminution in the Response to Nutrients as Insulin-releasing Agents During the Early Neonatal Period in the Rat
Authors: Grill V , Lake W , Freinkel N 
Published: September 2013

Glucose-induced insulin secretion is diminished during the fetal and neonatal period. To investigate whether the “defect” in B-cell secretion is specific for glucose and linked to glucose metabolism, the insulin-releasing effect of three nutrient secretagogues, glucose, glyceraldehyde, and leucine, were compared at different ages of the rat in vivo (1- and 7-day neo-nates) and in vitro (1- and 7-day neonates and adult animals). Intraperitoneal injections produced a marked insulin response to glucose, glyceraldehyde, and leucine in 7-day animals but only small increments that were not significant in 1-day neonates.
The accumulation of insulin from isolated islets of 1-day neonates during 60-min incubations was slightly but significantly enhanced by 11.1-34.4 m M glucose or 40 mM leucine. No response was seen with 1-16 mM glyceraldehyde. By contrast, all three secretagogues markedly stimulated insulin secretion from 7-day and adult islets. However, quantitative relationships differed. Thus, the response from 7-day islets to the highest concentration of glucose was 20%, to glyceraldehyde 10%, and to leucine 50% of adult values. A “basal” concentration of glucose (4.4 mM) amplified glyceraldehyde- or leucine-induced insulin release, but did not influence the age-related differences in secretory response.
The nutrient secregogues induced a small percent stimulation of (32P)-orthophosphate efflux from prelabeled islets of 1-day neonates. This stimulation increased progressively with age. However, in 1- and 7-day islets glucose and leucine stimulated the efflux of 32P more than glyceraldehyde; in adult islets the nutrients were equipotent. Glucose, glyceraldehyde, and leucine increased the accumulation of (3H) cyclic AMP in prelabeled adult but not in 7- or 1-day islets.
The foregoing indicates that the obtunded insulin secretion at birth in the rat may apply to all nutrient secretagogues. Because of the difference in metabolic disposition of tested secretagogues, the secretory limitation cannot be ascribed to faulty glycolysis but must involve some communally shared, probably early, step in stimulus-secretion coupling. Continued maturation includes preferential development of the secretory responsiveness to some secretagogues.
Organ Culture of Fetal Mouse Pancreas: The Effect of Culture Conditions on Insulin and Glucagon Secretion
Authors: Collier S , Mandel T E , Hoffman L , Caruso G 
Published: September 2013

Seventeen-day-old mouse pancreas was grown in organ culture under various culture conditions and the insulin released into the medium, either chronically or during acute incubations, was measured. Three media, DME, RPMI 1640, and TC199, were tested, each at glucose concentrations of 1, 2, 3, and 4 g/L. Fetal pancreata maintained in RPMI 1640 at 4 g/L glucose secreted the most insulin over a 25-day period. Tissue grown in RPMI 1640 and DME secreted more insulin in higher glucose concentrations, but explants grown in TC199 secreted low levels of insulin regardless of glucose concentration. Fetal pancreata grown in medium supplemented with 5% FCS secreted less insulin in acute incubations than tissues grown in 10%, 15%, 20%, or 30% FCS, which secreted equivalent amounts. There was no difference in the amount of insulin released by islets grown in media supplemented with 15% FCS from four different batches.
Although fetal islets grown in high glucose concentrations generally secreted more insulin (and less glucagon) than “normoglycemic” controls, their ability to release insulin in subsequent acute incubations was impaired. Explants, which had been maintained for 2 wk in 2.5 or 4 g/L glucose and a further 3 days in normoglycemic medium, secreted less insulin and glucagon in acute release exeriments than tissue maintained in 1 g/L glucose throughout.
Light microscopy of cultured fetal pancreas showed that tissue remained viable at all glucose concentrations tested and differences in response could not be attributed to selective necrosis. Tranplantation of cultured islets indicated that tissue grown under normoglycemic conditions functioned better than tissue grown in hyperglycemic media.
Correction of Exercise-induced Microalbuminuria in Insulin-dependent Diabetics After 3 Weeks of Subcutaneous Insulin Infusion
Authors: Viberti Giancarlo , Pickup John C , Bilous Rudolf W , Keen Harry , Mackintosh David 
Published: September 2013

The effect of metabolic near-normalization, induced by continuous subcutaneous insulin infusion, on the exaggerated microalbuminuria of exercise was studied in eight insulin-dependent diabetic men selected for normal resting albuminuria. Patients were studied in randomized order during the ordinary glycemic control of conventional insulin treatment (CIT) and after 3 wk of “super-control” with continuous subcutaneous insulin infusion (CSII). Seven age-matched healthy men were used as controls. In the diabetics the albuminuric response to fixed-load bicycle exercise (600 kpm/min for 20 min) during CIT greatly exceeded that of the normal controls (P &lt; 0.01). After 3 wk of optimal plasma glucose control, urinary albumin excretion rates in response to the same exercise load were significantly reduced (P &lt; 0.02) in the diabetics and became statistically indistinguishable from that of the normal controls. The urinary excretion rate of β2-microglobulin, an index of tubular function, was not increased significantly by exercise either during CIT or CSII.
The plasma glucose fall after exercise was greater (P &lt; 0.001) on CIT (8.5 ± 0.9 mmol/L) than on CSII (4.0 ± 0.6 mmol/L). The pulse rate acceleration in response to exercise was significantly reduced after 3 wk of CSII (P &lt; 0.05). The exercise-induced systolic blood pressure rise was similar in controls and diabetics on both therapeutic regimens.
Thus, a period of metabolic near-normalization in the diabetic corrects the abnormal transglomerular passage of albumin induced by moderately strenuous muscular exercise and reduces the exercise tachycardia. Improved control with CSII appears to reduce greatly the risk of exercise-induced hypoglycemia, despite much tighter glycemic control.
Subcutaneous, Isogeneic Transplantation of Duct-ligated Pancreas in Streptozotocin-Diabetic Mice: Relationships Between Carbohydrate Tolerance and Hormone Content in Transplant or Host Pancreas
Authors: Kramp Robert C , Burr Ian M 
Published: September 2013

Mice with subcutaneous, isogeneic transplants of duct-ligated pancreas from either two or five donors displayed impaired glucose tolerance to gastric or intravenous glucose, or to an overnight fast followed by a 15-min meal of mouse food. Compared with peripheral insulin responses in normal controls, those of transplant recipients were less after gastric or intravenous glucqse, but no different after the meal. Despite normalization of peak insulin levels in the peripheral circulation of isografted mice, glucose clearance was still impaired and this probably resulted, in part, from a relative insufficiency of insulin in the portal circulation. Results of glucose tolerance tests, after transplant recipients consumed a relatively small amount of food, suggested that near-normal glucose homeostasis may be present for these mice under normal feeding conditions.
In mice that received incremental doses of streptozotocin, impaired glucose tolerance to a meal was observed if pancreatic insulin content fell below 26% of normal. We failed to show a similar relationship between glucose tolerance and pancreatic insulin content in transplant recipients since all showed impaired glucose tolerance. Despite the initial transplantation of different amounts of islet tissue, at termination insulin content (transplant plus endogenous pancreas) was essentially the same for all recipients, totaling 19–22% of that found in a normal mouse pancreas.
Nonenzymatic Glycosylation of Low Density Lipoproteins In Vitro: Effects on Cell-interactive Properties
Authors: Gonen B , Baenziger J , Schonfeld G , Jacobson D , Farrar P 
Published: September 2013

Atherosclerosis occurs at an accelerated rate in patients with diabetes mellitus. Since some proteins undergo nonenzymatic glycosylation in diabetic patients and because certain chemical modifications of low density lipoproteins produced alterations in their interactions with certain cultgred cells, a fact that may be relevant to atherogenesis, we investigated the effect of in vitro glycosylation on cell-related properties of low density lipoproteins.
Glycosylation was carried out by incubating LDL (1–10 mg LDL-protein/ml) with glucose (0–100 mM) in 0.5 M phosphate buffer, pH 8.0, at 37°C. The amount of glucose incorporated into LDL after 1–2 wk of incubation was estimated to be in the range of 1–10 mol/mol LDL-protein. Amino acid analysis of glycosylated LDL showed that glucose was covalently bound to lysine residues.
In studies with cultured human fibroblasts, glycosylated LDL was internalized and degraded significantly less than control LDL, in proportion to the estimated degree of glycosylation (12% of control for the most extensively glycosylated LDL). Glycosylation of LDL also impaired significantly its ability to stimulate cholesteryl ester synthesis by cultured fibroblasts. Glycosylated LDL did not stimulate cholesteryl ester synthesis in rat peritoneal macrophages. If glycosylation of LDL occurs in diabetic patients, some pathophysiologic consequences related to the increased incidence of atherosclerosis in these patients may result.
Serum Glycosidase Activity in Diabetes Mellitus
Authors: Merimee Thomas J , Kennedy Allan Laurence , Mehl Thomas D , Rosenbloom Arlan 
Published: September 2013

The activity of three glycosidic enzymes, B-glucuroni-dase, N-acetylglucosaminidase, and B-galactosidase were measured in plasma samples from 163 diabetic subjects and 72 normal controls. No age- or sex-based variation in concentration was noted in controls. Plasma activity of B-glucuronidase and N-acetylglucosaminidase in diabetics correlated directly with the overall level of glycemia as measured by HbA1c levels. B-galactosidase activity was consistently normal in diabetics.
A significant age-based variation was noted in the diabetic group for B-glucuronidase and N-acetylglucosaminidase. Prior to age 12, B-glucuronidase and N-acetylglucosaminidase were normal in diabetics, but activity increased significantly after the age of 12, a change that appeared to coincide with the development Of puberty.
High Density Lipoproteins in Diabetes
Authors: Nikkilä Esko A 
Published: September 2013

The concentration of high density lipoproteins (HDL) in patients with diabetes mellitus is highly variable. Subnormal HDL cholesterol levels are present in untreated patients with insulin-deficient juvenile diabetes, but the values return to the normal range after beginning insulin therapy. During conventional subcutaneous insulin treatment the diabetic patients often exhibit increased mean HDL cholesterol concentrations, even in the presence of poor diabetic control. HDL concentration is not related to blood glucose or fast hemoglobin levels. However, in the presence of overt ketoacidosis and upon development of advanced diabetic nephropathy, HDL levels fall. In noninsulin-dependent diabetes low HDL cholesterol values are common, but they are associated more with obesity and hypertriglyceridemia than with the diabetic state itself. Thus, when diabetic and nondiabetic subjects are compared at similar relative body weight and serum triglyceride levels, there seems to be no difference in the mean HDL cholesterol values. The possible effects on HDL of treatment by diet and particularly by oral antidiabetic agents are not yet clear; published results are controversial in this respect.
Alterations of HDL in diabetes are probably based on the presence of insulin deficiency or, more commonly, on hyperinsulinemia and insulin resistance. HDL (particularly the subfraction HDL2) concentration is regulated by two endothelial lipolytic enzymes, lipoprotein lipase and hepatic lipase, both of which are insulin sensitive. Peripheral hyperinsulinemia is produced in insulin-dependent diabetics by insulin treatment. This results in an increase of tissue lipoprotein lipase activity, which in turn augments HDL levels. In obese diabetic patients the peripheral tissues are resistant to insulin and, accordingly, the lipoprotein lipase activity is subnormal. Furthermore, the hepatic lipase activity is often increased and may contribute to the lowering of HDL by increased removal of HDL cholesterol. It is not known whether the alterations of HDL play any role in the increased atherosclerosis of diabetic patients.
Hypertension: The Major Risk Factor in Juvenile-onset Insulin-dependent Diabetics
Authors: Richard Christlieb A , Warram James H , Królewski Andrzej S , Busick Edward J , Ganda Om P , Asmal Abdul C , Stuart Soeldner J , Bradley Robert F 
Published: September 2013

The prevalence of hypertension in various age groups of diabetics and its role as a risk factor in juvenileonset insulin-dependent diabetics followed for 40 yr after diagnosis was evaluated. The results show clearly that hypertension is more prevalent in diabetics of any age after age 24 yr than in the general population.
In this type of diabetes, although death due to renal disease occurs earlier than that due to coronary heart disease, both causes of death are significantly related to hypertension. Those patients with an onset of diabetes 13 yr of age or younger can expect to live longer following the diagnosis of diabetes mellitus than those with an onset after 13 yr of age, perhaps because hypertension appears at about the same age in both groups. Case/control analysis of the data shows that survivors have significantly less hypertension than those dying of renal or cardiac disease. Furthermore, the close temporal relationship between the onset of hypertension and the onset of proteinuria in patients with either renal or coronary deaths suggests that the hypertension in these patients is renal in origin.
Two other risk factors, smoking and serum lipids, were evaluated in this population. From the data thus far accumulated, neither smoking nor lipids appear to influence mortality significantly. We conclude that hypertension is the major additive risk factor for mortality in juvenile-onset insulin-dependent diabetics.
Pericyte Degeneration and Basement Membrane Thickening in Skeletal Muscle Capillaries of Human Diabetics
Authors: Tilton Ronald G , Hoffmann Phyllis L , Kilo Charles , Williamson Joseph R 
Published: September 2013

Pericyte distribution and capillary dimensions were determined in tissue obtained at autopsy from human pectoral, abdominal, quadriceps femoris, and gastrocnemius muscle of 20 diabetics and 20 age- and sex-matched nondiabetics. Tissue was processed for electron microscopy, and morphometric data obtained from electron micrographs were used to calculate capillary circumference, the percentage of capillary circumference covered by pericytes, and capillary basement membrane width (CBMW). The numbers of vessels containing pericytes and the number of pericyte processes per vessel were tabulated as indices of pericyte distribution along capillaries. The presence of cellular debris within capillary basement membranes was tabulated as an index of pericyte necrosis.
Capillary circumference did not differ for controls and diabetics and did not vary between muscles from either group. CBMW was consistently thicker in diabetics than in controls and differences were greatest in lower extremity muscles. Pericytes were associated with virtually all vessels in lower extremity muscles of both normal and diabetic subjects. Although no differences were observed between controls and diabetics for each muscle examined, pericyte circumferential coverage of capillaries, as well as numbers of pericyte processes per capillary, increased significantly in the direction of head to foot for both controls and diabetics, paralleling increases in CBMW. Pericyte debris within capillary basement membranes also increased significantly in the direction of head to foot in both controls and diabetics and, in addition, occurred much more frequently in diabetics than in controls, with the greatest differences present in lower extremity muscles.
These observations indicate that pericyte frequency and coverage of capillaries vary between different skeletal muscles, but not between controls and diabetics. These findings, coupled with the increased frequency of pericyte debris within capillary basement membranes of diabetics, suggest that: (1) pericyte degeneration and turnover are increased in skeletal muscle capillaries of diabetics, arid (2) pericyte degeneration is not limited to the retina in diabetes mellitus. A strong correlation between the presence of pericyte debris and capillary basement membrane thickening suggests that both may be linked to a common pathogenetic factor.
Islet Secretion in a New Experimental Model for Non-insulin-dependent Diabetes
Authors: Weir G C , Clore E T , Zmachinski C J , Bonner-Weir S 
Published: September 2013

An animal model of diabetes mellitus has been developed in which neonatal rats are injected with streptozotocin at 2 days of age. After transient hyperglycemia followed by near normal glycemia, these animals develop nonketotic diabetes at about 6 wk of age that does not require insulin treatment. Secretion from the endocrine pancreas of 6–15-wk-old rats was evaluated with the isolated, perfused pancreas technique.
Insulin secretion responded very poorly to high perfusate glucose concentrations, but in the presence of theophylline this meager response was enhanced. In contrast, arginine elicited an insulin response comparable to that of the control rats. Isoproterenol stimulated insulin secretion more in the diabetic model than in the controls, and tolbutamide failed to evoke insulin secretion. Glucagon secretion in response to arginine and isoproterenol was similar in both groups, but was suppressed less efficiently by glucose in the model than in controls. Evidence for enhanced basal secretion of somatostatin was also found. Thus, these hyperglycemic rats have a selective defect in glucosestimulated insulin secretion with preservation of responses to other agents. In addition, abnormalities in the secretion of glucagon and somatostatin have been found.
Hormonal, Metabolic, and Cardiovascular Responses to Hypoglycemia in Diabetic Autonomic Neuropathy
Authors: Hilsted J , Madsbad S , Krarup T , Sestoft L , Christensen N J , Tronier B , Galbo H 
Published: September 2013

Hormonal, metabolic, and cardiovascular responses to insulin-induced hypoglycemia were investigated in 10 juvenile-onset diabetics who showed signs of autonomic neuropathy, in 8 control patients of similar age and duration of diabetes without neuropathy, and in 6 healthy subjects. In an attempt to normalize intermediary metabolism, the diabetics were treated with soluble insulin only (given subcutaneously and intravenously) for 48 h preceding the study.
Plasma epinephrine concentrations were significantly lower in patients with autonomic neuropathy before the experiment as well as 15 min after serum glucose nadir compared with diabetics without neuropathy (P &lt; 0.05), indicating impaired sympathoadrenal activity. Plasma norepinephrine responses did not differ significantly. No significant increase was found in glucagon concentrations in patients with autonomic neuropathy, whereas a small increment was found in diabetics without neuropathy. Growth hormone and cortisol responses were similar in the two patient groups, and serum free insulin concentrations were also similar. In spite of blunted responses of glucagon and of epinephrine in the patients with autonomic neuropathy, serum glucose responses were similar to those of the diabetics without autonomic neuropathy. Furthermore, rate of lipolysis, as judged from FFA and glycerol concentrations, as well as systolic blood pressure increments were significantly greater (P &lt; 0.05) in patients with autonomic neuropathy than in diabetics without neuropathy.
In conclusion, during insulin-induced hypoglycemia, patients with autonomic neuropathy had impaired activation of the adrenal medulla, probably due to sympathetic neuropathy. Furthermore, they had no increase in glucagon concentrations. Compared with noneuro-pathic diabetics, serum glucose recovery was unaffected and lipolytic responses and blood pressure increments were exaggerated, suggesting increased sensitivity of hepatic glycogenolysis, adipose tissue lipolysis, and the cardiovascular system toward the action of catecholamines in diabetics with autonomic neuropathy.
Correlation of Urinary Excretion of C-Peptide with the Integrated Concentration and Secretion Rate of Insulin
Authors: Meistas Mary T , Zadik Zvi , Margolis Simeon , Avinoam Kowarski A 
Published: September 2013

The secretion rate of insulin (SR-I) of 50 normal subjects was calculated from the 24-h integrated concentration of insulin (IC-I), the peripheral metabolic clearance of insulin (pMCR-l), and the mean fractional hepatic insulin extraction (fhMCR-l) that was derived from our data. fhMCR-l was determined as the difference in the molar secretory rate of C-peptide (SR-C) and the molar peripheral clearance of insulin (pMCRI × IC-I) divided by SR-C. The IC-I in our 50 subjects was 1.19 ± 0.38 ng/ml and the IC-C was 2.93 ± 0.58 ng/ml. Based on these data, the fhMCR-l was 0.40 and the SR-I was estimated to be 54.8 ± 18.0 U/24 h.
The 24-h urinary C-peptide excretion (U-C), 44.9 ± 20.4 μg/24 h, had a statistically significant correlation with SR-I (r = 0.838, P &lt; 0.0001), while the IC-I correlated significantly with the 24-h urinary C-peptide/g of creatinine (r = 0.823, P &lt; 0.0001). The U-C may thus serve as a practical method for estimating the SR-I.