bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diabetic Neuropathy in the Mutant Mouse [C57BL/ks(db/db)]: A Morphometric Study
Authors: Robertson David M , Sima Anders A F 
Published: September 2013

Detailed studies of peripheral nerves were undertaken in the mutant diabetic mouse of the [C57BL/ks(db/db)] strain using electrophysiologic and morphometric techniques.
Electrophysiologic studies showed severely impaired motor nerve conduction velocity (MNCV), which developed promptly during the early phase of the diabetic syndrome. Morphometric changes occurred first after 20 wk of diabetes in both myelinated and unmyelinated fibers. There were both loss and shrinkage of myelinated fibers, most pronounced in the sural nerve and the ventral root. Changes appeared late in the dorsal root and in the peroneal and vagus nerves. Unmyelinated fibers showed both shrinkage and loss of axons, presumably involving sympathetic and afferent somatic fibers.
Teased fiber studies and calculations of axon-myelin ratios confirmed our earlier suggestion18 that the neuropathy is primarily axonal in nature.
The temporal discrepancy between functional and structural impairments in the present model strongly suggests a metabolic cause of the early neuropathy. This was further supported by the positive effect of insulin treatment on MNCV during the early phase of diabetes, whereas, during the late phase, treatment failed to show any effect.
Resistance to Insulin but Not to Glucagon in Lean Human Hypertriglyceridemics
Authors: Steiner George , Morita Soichiro , Vranic Mladen 
Published: September 2013

SUMMARY
Glucose kinetics were studied in a group of nonobese humans with endogenous hypertriglyceridemia before, during, and after an infusion of graded increments of glucagon. The tracer methods employed permitted glucose turnover to be quantitated under non-steady state conditions. The rates of glucose production, disappearance, and fractional disappearance were related to the range of glucagon and insulin levels in each individual. The findings in hypertriglyceridemics were compared with those in lean normals of the same relative body weight and the same extracellular fluid volume per kg, as reflected by their apparent glucose space. Glucose production and serum insulin were each positively correlated to plasma glucagon concentrations in both hypertriglyceridemics and normals. Thus, with respect to these parameters, the hypertriglyceridemics were not resistant to glucagon. During the glucagon infusion, the glucose concentration rose more in the hypertriglyceridemics than in the normals because of a reduced total rate of glucose disappearance in the hypertriglyceridemics. In the normals the fractional disappearance rate of glucose was positively related to serum levels of insulin, whereas in the hypertriglyceridemics it was lower than normal and did not change in relation to insulin concentration. This demonstrated that, at least with respect to glucose utilization, lean hypertriglyceridemics can be resistant to insulin even in the absence of obesity.
Glucose Intolerance Due to Insulin Resistance in Patients with Spinal Cord Injuries
Authors: Duckworth William C , Solomon Solomon S , Jallepalli Panduranga , Heckemeyer Chris , Finnern James , Powers Alvin 
Published: September 2013

SUMMARY
Glucose intolerance occurs frequently in patients with spinal cord injury (SCI). To characterize this better, 45 patients with spinal cord injuries received oral glucose tolerance tests (OGTT). The subjects with glucose intolerance had significantly higher insulin levels than either the glucose-tolerant or normal control subjects.
Since hyperinsulinism in the presence of glucose intolerance suggests insulin resistance, the peripheral insulin activity (A) was calculated from the OGTT data. The glucose-intolerant SCI patients had significantly lower A values than the other groups. The most resistant SCI subjects (A&lt;0.3) also had resistance to exogenous insulin. In 18 subjects receiving insulin tolerance tests, the A value calculated from the OGTT was 100% accurate in predicting the presence of sensitivity or resistance to exogenous insulin. In spite of the presence of insulin resistance, however, 125I-insulin binding to SCI patients' circulating monocytes was not significantly different from that in control subjects.
Effects of Acute Insulin Deficiency on Glucose and Ketone Body Turnover in Man: Evidence for the Primacy of Overproduction of Glucose and Ketone Bodies in the Genesis of Diabetic Ketoacidosis
Authors: Miles John M , Rizza Robert A , Haymond Morey W , Gerich J E 
Published: September 2013

SUMMARY
To assess the relative contribution of overproduction and underutilization of glucose and ketone bodies to the development of diabetic ketoacidosis in man, the effects of acute insulin deficiency on glucose and ketone body turnovers were determined in seven ketosis-prone (type I) diabetic subjects. After termination of prolonged intravenous infusions of insulin, which had been maintaining the subjects euglycemic, plasma free insulin decreased from 18 ± 4 μU/ml to 7 ± 1 μU/ml, P &lt; 0.01; plasma glucagon increased from 67 ± 6 pg/ml to 259 ± 67 pg/ml, P &lt; 0.05, but plasma growth hormone and cortisol did not increase. Plasma glucose increased from 5.4 ± 0.3 mM to 15.6 ± 1.0 mM, P &lt; 0.01; plasma ketone bodies (β-hydroxybutyrate plus acetoacetate) increased from 1.4 ± 0.4 mM to 7.2 ± 1.5 mM, P &lt; 0.01. Glucose production increased abruptly from 13.2 ± 1.1 μmol/kgmin to a maximum of 26.1 ± 2.9 μmol/kg-min at 2 h but then decreased toward baseline rates; glucose utilization also increased transiently. In contrast, both ketone body production and utilization increased progressively throughout the study from 5.4 ± 1.4 and 5.5 ± 1.1 to 18.3 ± 3.9 and 14.7 ± 2.1 μmol/kg-min, respectively, P &lt; 0.01. Clearance of both glucose and ketone bodies decreased more than 50%, P &lt; 0.01. These results indicate that overproduction of glucose and ketone bodies is the primary process involved in the initiation of diabetic ketoacidosis in man. However, persistent overproduction of glucose and ketone bodies may not be necessary for the maintenance of hyperglycemia and hyperketonemia, since clearance of both substrates is impaired. Finally, since, of all counter-insulin hormones measured, only plasma glucagon increased coincident with increases in glucose and ketone body production, these results provide further evidence that glucagon may be the most important counter-insulin hormone involved in the genesis Of ketoacidosis.
Multiple Redox Forms of the Insulin Receptor in Native Liver Membranes
Authors: Massagué Joan , Czech Michael P 
Published: September 2013

SUMMARY
Three forms of disulfide-linked insulin receptor complexes are labeled by covalent cross-linking to receptor- bound 125I-insulin in native adipocyte or liver membranes. These receptors of Mr 350,000, Mr 320,000, and Mr 290,000 are composed of α(Mr 125,000), β(Mr 90,000), and β1(Mr 49,000) subunits in stoichiometries of (αβ)2, (αβ)(αβ)1 and (αβ1)2, respectively. In adipocyte membranes, these receptor structures can undergo a first step of reduction by dithiothreitol, dissociating into Mr 210,000 (αβ) and Mr 160,000 (αβ1) partially reduced receptor fragments. Complete dissociation of such fragments into the free α,β , and β1 receptor subunits is achieved at high reductant concentrations. In liver plasma membranes the partially reduced receptor species of Mr 210,000 and Mr 160,000 are observed even when electrophoresis is performed under nonreducing conditions. This observation indicates that native liver plasma membranes contain multiple redox states of the high affinity insulin receptor.
Glucocorticoid-induced Recovery from Streptozotocin Diabetes in the Adult Rat
Authors: Roudier Michel , Portha Bernard , Picon Luc 
Published: September 2013

The effect of a large dose of cortisol (5 mg/kg), injected 24h and 3h before or 3h and 24h after streptozotocin (SZ), on the course of SZ-induced diabetes has been studied in the rat. Glucose tolerance tests, performed 1 or 2, 8, and 30 days after the SZ injection (35 mg/kg), gave the same results in cortisol-treated rats regardless of the time of cortisol injection [before SZ (C.SZ) or after it (SZ.C)]. During the first test, elevated plasma glucose, decreased glucose tolerance, and decreased glucose-induced insulin secretion were present in SZ, C.SZ, and SZ.C rats. During the second and the third tests, glucose tolerance and insulin secretion were significantly improved in both groups of cortisol-treated rats. On the contrary, rats receiving only SZ showed a worsening of the diabetic state. It should be noted that cortisol-induced recovery of diabetes was not obtained with larger doses of SZ (50 mg/kg).
These findings indicate that an improvement of diabetes can be obtained by cortisol treatment after the onset of chemically induced diabetes. Whether this effect is obtained through an effect on pancreatic regeneration and/or through the anti-inflammatory properties of glucocorticoids is unknown at the present time.
Altered Responsiveness to Cortisol, Epinephrine, and Glucagon in Insulin-infused Juvenile-onset Diabetics: A Mechanism for Diabetic Instability
Authors: Shamoon Harry , Hendler Rosa , Sherwin Robert S 
Published: September 2013

To evaluate the mechanism of rebound and stress hyperglycemia in diabetes, cortisol, epinephrine, and glucagon were infused into normal and juvenile-onset diabetic subjects for 5–6 h in doses designed to simulate the increments observed in insulin hypoglycemia or severe stress. Plasma glucose and glucose kinetics were normalized in the diabetics before each experiment by infusion of insulin (0.25–1.0 U/h) for 4–6 h, which was then continued during anti-insulin hormone administration.
Infusion of cortisol and epinephrine produced comparable elevations in plasma cortisol (35–45 /μg/dl) and plasma epinephrine (350–450 pg/ml) in normal and diabetic subjects. However, the increment in plasma glucose in diabetics after cortisol (86 ± 15 mg/dl) and epinephrine (129 ± 12 mg/dl) infusion was fivefold to sevenfold greater than it was in normals (P &lt; 0.001), despite ongoing insulin infusion. Whereas cortisol failed to alter glucose production in normals, in diabetics there was a progressive 35% increase in glucose production (P &lt; 0.001). Similarly, epinephrine produced only a transient (&lt;90 min) 60% rise in glucose production in normal subjects, but caused a sustained 50%–90% rise in glucose production in diabetics throughout the entire 5-h study. In contrast, both cortisol and epinephrine infusion was accompanied by a 25%–40% (P &lt; 0.001) decline in glucose clearance, no different than in normal and diabetic subjects. Glucagon infusion produced a transient 35%–40% rise in glucose production, which was of comparable magnitude and duration in normal controls and diabetics. However, the glucagon-induced rise in plasma glucose was threefold greater in the diabetics due to failure of endogenous insulin secretion and consequent lack of an increase in glucose clearance as observed in normal controls. When saline was administered to the insulin-infused diabetics, neither plasma glucose nor glucose production were altered from baseline values.
It is concluded that (1) the hyperglycemic effect of each of the anti-insulin hormones is increased in diabetics, in spite of prior normalization of plasma glucose concentration, by continuous insulin infusion and (2) hyperglycemia is particularly exaggerated by elevations of cortisol and epinephrine in diabetes as a consequence of an altered response of the liver to these hormones.
Duodenal Contribution to Pancreaticoduodenal Vein Islet Hormones During Stimulation of the Canine Pancreas with Calcium
Authors: Hermansen K 
Published: September 2013

The possible influence of the duodenum on pancreatic hormones in the pancreaticoduodenal venous effluent of the canine pancreas was studied. The magnitude and dynamics of somatostatin, glucagon, and insulin responses during stimulation with 5 mM calcium were identical whether or not the duodenal remnant was excluded from the perfusion by clamping.
The results indicate that during perfusion with calcium the duodenal remnant is without any significant regulatory or contributory role on pancreatic hormone secretion from the isolated canine pancreas preparation.
Immunohistochemical Localization of Aldose Reductase: II. Rat Eye and Kidney
Authors: Ludvigson Mark A , Sorenson Robert L 
Published: September 2013

Aldose reductase (AR) was purified from rat seminal vesicles. Specific antibodies to this enzyme were prepared in rabbits and were used in the unlabeled antibody-enzyme (PAP) technique to localize AR in a number of tissues known to be sites of diabetic lesions. AR was localized in the following structures in the eye: lens epithelial lining and cortical lenticular fibers; corneal endothelium; the inner, nonpigmented layer of ciliary body epithelium and its extension as the posterior surface of the iris; and neuroglial (Muller) cells in the retina. Retinal capillary endothelium did not contain immunoreactive AR.
In the kidney, staining was intense in the inner medulla. Specific structures included thin limbs of the loop of Henle, collecting tubules deep in the inner medulla, and transitional epithelial cells lining the pelvic space: structures in the cortex included gtomerular podocytes and distal convoluted tubules. Collecting tubules in the outer medulla and cortex, as well as proximal convoluted tubules and glomerular capillary endothelium did not contain immunoreactive AR.
Amelioration of Mesangial Volume and Surface Alterations Following Islet Transplantation in Diabetic Rats
Authors: Steffes Michael W , Brown David M , Basgen John M , Mauer S Michael 
Published: September 2013

Highly inbred Lewis rats with streptozotocin-induced diabetes mellitus of 7 mo duration received intraportal transplants of neonatal pancreatic tissue. At 7 and 9 mo of diabetes (at the time of and at 2 mo after islet transplantation) renal biopsies for the evaluation of several morphometric parameters were obtained from control (C), diabetic-nontranspianted (D), and diabetic-transplanted (D-T: with normal plasma glucose values) rats.
Glomerular volume in D-T animals at 9 mo fell to a value less than that in C rats while glomerular volume in D animals exceeded that in C rats at both 7 and 9 mo. Electron microscopic morphometry of the total mesangium and its cellular and matrix components documented a nearly twofold increase in the volume of the mesangial matrix in D as compared with C rats at both 7 and 9 mo. While the mesangial cellular component was also increased in diabetes, the changes in the volume of the mesangial matrix in D rats at both 7 and 9 mo provided the major proportion of the increased volume of the total mesangium. With islet transplantation, significant reduction in the volumes of the mesangial matrix and a much smaller and not significant decrease in the cellular component gave normal values for those components and for the volume of the total mesangium in D-T animals.
The expanded volume of the total mesangium in diabetes concomitantly increased the proportion of the glomerular capillary surface interfaced with the mesangium. Similarly, the proportion of the glomerular basement membrane (GBM)-epithelium interface juxtaposed to the mesangium was elevated in diabetes. These two observations imply that the expanding mesangium interposed itself between the endothelial cells and the GBM, increasing the surface of the mesangium. With islet transplantation these surface alterations returned toward normal in conjunction with the reduction in volume of the mesangium.
These observations with electron microscopic morphometry provide detailed documentation of the alterations in the mesangium of experimental diabetes mellitus. The sensitivity with which these changes can be monitored permit detailed analysis of subtle increases in both mesangial surface and volume in diabetes mellitus.
The Contrasting Responses of Splanchnic and Renal Glucose Output to Gluconeogenic Substrates and to Hypoglucagonemia in 60-h-fasted Humans
Authors: Björkman Ola , Felig Philip , Wahren John 
Published: September 2013

SUMMARY
Arterial concentrations and splanchnic as well as renal exchange of glucose, lactate, pyruvate, glycerol, and alanine were studied in the basal state and during intravenous infusion of alanine or glycerol in healthy subjects who had fasted for 60 h. After 45 min of infusion of alanine or glycerol, somatostatin administration (SRIF, 9 μg/min) was added to induce hypoglucagonemia.
Alanine infusion, at a rate of 1 mmol/min, was accompanied by an 80% rise in splanchnic glucose output (SGO) and a small (16%) rise in arterial glucose. Splanchnic alanine uptake, which rose fivefold to sixfold above basal, could account for the entire rise in SGO. Intravenous administration of glycerol (1 mmol/min) resulted in an elevation of blood glucose (+ 9%) but no significant change in SGO, even though glycerol uptake by the splanchnic tissues rose eightfold above basal levels.
Measurements of renal exchange of glucose indicated a small but statistically significant release of glucose from the kidney (0.04 ± 0.01 mmol/min) in the basal state, which accounted for 10% of total (renal plus splanchnic) glucose production. Administration of glycerol at a rate of 2 mmol/min resulted in a rise in renal glucose output to 0.16 ± 0.03 mmol/min, which could be accounted for in its entirety by renal glycerol uptake. In contrast, infusion of alanine (2 mmol/min), did not alter the renal glucose exchange.
Infusion of SRIF was accompanied by a significant fall in the arterial glucagon level in all studies. Concomitante, large decreases in arterial glucose and SGO were observed during both alanine and glycerol administration. However, splanchnic uptake of gluconeogenic precursors was not influenced by SRIF administration. The elevated renal glucose output seen during glycerol administration was not altered by SRIF infusion.
It is concluded that, in 60-h-fasted man, (a) renal glucose output contributes significantly to total glucose production, (b) administration of glycerol stimulates renal glucose production, (c) alanine infusion increases splanchnic but may not affect renal glucose output, and (d) hypoglucagonemia inhibits splanchnic but not renal glucose output. These data indicate that hepatic and renal gluconeogeneses respond differently with respect to stimulation by specific substrates and to their dependence on basal glucagon levels.
The Role of Calcium in Alpha-adrenergic Inactivation of Glycogen Synthase in Rat Hepatocytes and its Inhibition by Insulin
Authors: Strickland Garrison W , Blackmore Peter F , Exton John H 
Published: September 2013

SUMMARY
The effects of epinephrine, vasopressin, and A23187 on glycogen synthase and phosphorylase were examined in isolated rat liver parenchymal cells from fed animals. In normal calcium-containing hepatocytes, epinephrine, vasopressin, and A23187 were more potent at inactivating glycogen synthase, previously activated with 30 mM glucose, than at activating phosphorylase. In calcium-depleted hepatocytes (cells washed and incubated with 1 mM EGTA), the effect of epinephrine on both enzyme activities was impaired, while the effects of vasopressin and A23187 were completely abolished. Insulin was more effective at inhibiting the effects of epinephrine in calcium-depleted cells, but it was without effect on vasopressin and A23187 actions. The ability of epinephrine, vasopressin, and A23187 to elicit calcium efflux from cells was not altered by the presence of 30 mM glucose. These findings are consistent with the idea that the α-adrenergic inactivation of liver glycogen synthase may be a result of the increased stimulation of a calcium-dependent protein kinase, possibly phosphorylase b kinase.
Increased Integrated Concentration of Norepinephrine, Epinephrine, Aldosterone, and Growth Hormone in Patients with Uncontrolled Juvenile Diabetes Mellitus
Authors: Zadik Zvi , Kayne Richard , Kappy Michael , Plotnick Leslie P , Avinoam Kowarski A 
Published: September 2013

SUMMARY
The 24-h integrated plasma concentration of glucose (IC-glucose), norepinephrine (IC-NE), epinephrine (IC-E), cortisol (IC-F), growth hormone (IC-QH), aldosterone (IC-ALDO), and plasma renin activity (IC-PRA) were measured in 11 nonobese juvenile-onset nonke-totic diabetic patients exhibiting hyperglycemie and glycosuria and 34 matched control subjects using a portable pump, drawing blood at a constant rate through a nonthrombogenic i.v. catheter. The diabetic patients had a noticeable rise of their IC-NE, IC-E, IC-GH, and IC-ALDO. There was no significant difference between the IC-F and IC-PRA of the patients and the control subjects.
Failure of Cortisol Blockade to Inhibit Early Morning Increases in Basal Insulin Requirements in Fasting Insulin-dependent Diabetics
Authors: Bright George M , Melton Terry W , Rogol Alan D , Clarke William L 
Published: September 2013

SUMMARY
Overnight basal insulin requirements to maintain euglycemia were determined in five insulin-dependent diabetic subjects using a closed-loop insulin infusion system. A significant increase in hourly insulin requirements occurred between 0600 h and 0900 h as compared with 0100 h–0600 h. Although the increased insulin requirement was coincident with only the physiologic diurnal increase in plasma cortisol, the oral administration of the 11-beta hydroxylase inhibitor, metyrapone, decreased only the total overnight (0100 h–0900 h) basal insulin requirement, but not the early morning (0600 h-0900 h) rise in insulin required to maintain euglycemia. It would appear that although cortisol is an important counterregulatory factor, its diurnal elevation cannot account for the increase in early morning basal insulin requirements to maintain euglycemia in insulin-dependent diabetics.
Insulin-like Effect of Zinc on Adipocytes
Authors: Coulston L , Dandona P 
Published: September 2013

SUMMARY
In view of the known effect of zinc on the crystalline nature of insulin, we have investigated whether zinc alters the biologic potency of this hormone. Using the rate of lipogenesis by rat epididymal adipocytes as an index of the biologic potency of insulin, we have shown that zinc exerts a potent stimulatory effect upon lipogenesis in vitro similar to, but quite independently of, insulin and that it has an additive effect with that of insulin when both are incubated together. This effect of zinc on adipocytes and the biologic potency of insulin, hitherto unreported, is of significance at the biologic, pharmacologie, and clinical level.