bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Chronic Administration of Sodium 2 Chloropropionate in Normal and Diabetic Dogs
Authors: Ribes G , Valette G , Valette J F , Loubatieres-Mariani M M 
Published: September 2013

SUMMARY
Pancreatic hormonal and metabolic responses to chronic administration of sodium 2 chloropropionate (2 CP) were investigated in conscious dogs. We subcutaneously administered 2 CP daily for 7 days at the dose of 0.58 mmol/kg (62.5 mg/kg) in normal dogs and those rendered diabetic by injection of alloxan (0.24mmol/kg, i.v.).
In the normal dogs, the chronic administration of 2 CP provoked a decrease in blood lactate and pyruvate but not in blood glucose concentrations. Urinary oxalate was not increased by the daily injection of 2 CP. Blood ketone body concentrations progressively increased after the third day of treatment. At the same time, plasma cholesterol slowly decreased. The 2 CP chronic administration did not change the plasma somatostatin, glucagon, and insulin levels.
In the alloxan-diabetic dogs, treated with insulin alone, blood glucose, ketone body concentrations, and plasma somatostatin and glucagon levels were elevated. The adjunction of 2 CP with insulin injections resulted in a fall in blood lactate and pyruvate levels and a progressive decrease of blood glucose concentrations. Blood ketone bodies, which were already high at the start, were not affected when 2 CP was combined with insulin. The hypersomatostatinemia was not decreased, whereas the hyperglucagonemia was considerably reduced. So, I/G ratio, which was strongly decreased with insulin alone, progressively returned to normal values. As to urinary compounds, 2 CP induced a marked decrease in glucosuria and did not change the elevated urinary βhydroxybutyrate levels.
In conclusion, these findings show that the adjunction of sodium 2 chloropropionate to insulin in diabetic dogs results in a reduction of hyperglycemia and hyperglucagonemia.
Reversibility and Preventability of the Decrease in Slow Axonal Transport Velocity in Experimental Diabetes
Authors: Sidenius Per , Jakobsen Johannes 
Published: September 2013

The effect of insulin treatment on the slow axonal transport velocity of sciatic nerve was examined in streptozotocin-diabetic rats following the injection of 3H-proline into the fifth lumbar spinal ganglion. Strict insulin treatment, started immediately after the induction of diabetes and continued until the end of the experiment (group 1), can prevent the slowing in transport occurring in untreated diabetic rats [controls 0.98 ± 0.06 mm/day (mean ± SD); untreated diabetic rats 0.83 ± 0.10 mm/day; insulin-treated rats 1.00 ± 0.11 mm/day]. Strict insulin treatment when postponed for 3 wk (group 2), also can reverse an already slowed transport velocity (0.94 ± 0.05 mm/day). In addition, the influence on the transport abnormality of diabetes was studied in a situation where proteins were synthesized during normoglycemia and already in transport at the time of administration of streptozotocin; i.e., 2 days following protein labeling. The mean velocities were identical in rats made diabetic prior to (group 1) or following (group 2) protein labeling (0.83 ± 0.10 m/day and 0.83 ± 0.06 mm/day, respectively), Indicating that the metabolic derangement leads to a decrease in transport all along the axon as soon as the state is induced.
The percentage of TCA-insoluble label in slow component a (SCa) of the transport system was decreased in the three groups with elevated glucose level at the time of pulse-labeling (untreated group 1: 16.9 ± 8.3%; insulin-treated group 1 and 2:11.8 ± 8.1% and 10.3 ± 6.3%, respectively) as compared with rats with normoglycemia (controls: 27.4 ± 13.9% and untreated group 2: 35.1 ± 10.0%).
Thus a normal metabolic state at the time of pulselabeling followed by induction of hyperglycemia (diabetes group 2) results in decreased transport velocity of a normal amount of label, whereas the opposite metabolic situation (insulin-treated groups) leads to a normal transport velocity of a decreased amount of protein. We suggest that SCa is propelled by the continuous delivery of protein from the nerve cell body and, consequently, that the decreased amount of label in SCa as well as its slowed advancement indicate a defect in protein synthesis or in allocation of protein in the cell bodies.
Spontaneous Hyperglycemia and Impaired Glucose Tolerance in Athymic Nude BALB/c Mice
Authors: Zeidler Adina , Tosco Clara , Kumar Dinesh , Slavin Bernard , Parker John 
Published: September 2013

Basal plasma glucose, glucose tolerance, and insulin secretion were investigated in young and mature athymic nude BALB/c mice and in age-matched controls. Basal plasma glucose levels in male athymic nude mice were similar to those of controls at 1, 3, and 4 wk of age. At 6, 8, and 12 wk of age, male athymic nudes had significantly higher basal plasma glucose levels when compared with controls (P &lt; 0.01). Plasma immunoreactive insulin concentrations were similar in athymic nudes and controls at 1 wk of age, but at 3 wk of age and subsequently at 6, 8, and 12 wk athymic nude mice had significantly decreased insulin levels when compared with their age-matched controls (P &lt; 0.05).
We found impaired glucose tolerance in male athymic nude mice at all age groups when compared with both female athymic nudes and control BALB/c mice.
The discovery of a spontaneous diabetic syndrome (hyperglycemia, impaired glucose tolerance, and decreased insulin secretion) in a colony of athymic nude mice may provide an excellent model for studying the genetics and interactions between the immune and endocrine systems.
Glucoregulatory Mechanisms Following Hypophysectomy in Diabetic Dogs with Residual Insulin Secretion
Authors: Kemmer F W , Sirek A , Sirek O V , Perez G , Vranic M 
Published: September 2013

It is known that in pancreatectomized dogs completely deprived of insulin, hypophysectomy normalizes plasma glucagon and prevents ketoacidosis, but rarely normalizes glucose levels. The present study concerns diabetic dogs with only partial insulin deficiency in whom we studied the effects of hypophysectomy on glucoregulatory mechanisms. Eleven dogs were alloxanized and hypophysectomized 2–3 wk later. Withholding exogenous insulin from alloxan-diabetic dogs resulted in hypoinsulinemia (6 ± 1 μU/ml), hyperglucagonemia (341 ± 44 pg/ml), elevated plasma FFA levels (1442 ±125 μeq/ml), hyperglycemia (333 ± 27 mg/dl), increased hepatic glucose production (Ra, 4.2 ± 0.3 mg/kg/min) and decreased clearance of glucose (CR, 1.8 ± 0.1 ml/kg/min). After hypophysectomy, glucagon and FFA fell to normal in 7 of 11 hypophysectomized alloxan-diabetic dogs (106 ± 7), while 4 remained hyperglycemic (337 ± 28 mg/dl). Normoglycemia was the result of a reduced Ra to subnormal in the presence of unaltered glucose clearance. However, normoglycemia could not be equated with normal metabolism: glucose turnover was well below normal, and peripheral glucose uptake was impaired. The sensitivity of the liver to glucagon was investigated by infusing somatostatin alone (ST, 0.24 μg/kg/min) and with replacement (1 mg/kg/min) or with excess of glucagon (3.6 ng/kg/min). Even in hypophysectomized dogs, glucagon suppression resulted in a sustained decrease in Ra and plasma glucose. Glucagon replacement restored glucose kinetics and excess of glucagon led to hyperglycemia (300 ± 20 mg/dl). This was due to a prompt rise in Ra which, however, plateaued at levels lower than in diabetic dogs, suggesting that normalization of glucagon following hypophysectomy is an important but not the sole factor responsible for the marked reduction in Ra. The persistence of hyperglycemia in four diabetic dogs was attributed to a diminished effect of the hypophysectomy: in spite of hyperglycemia, Ra was not lower than in normoglycemic dogs, it was insensitive to glucagon suppression, and glucose clearance was more impaired than in normoglycemic dogs. It is hypothesized, therefore, that these dogs had a smaller residual insulin reserve than normoglycemic hypophysectomized dogs. Thus a critical amount of insulin may be indispensible for the maintenance of normoglycemia.
In conclusion, in alloxan-diabetic dogs, hypophysectomy can fully normalize postabsorptive glycemia, due to suppression of glucose production. Normoglycemia is, however, associated with an abnormally low glucose turnover. Hyperglucagonemia is important but not the sole factor responsible for diabetic overproduction of glucose. Hypophysectomy does not abolish the hepatic sensitivity to glucagon in insulin-deficient dogs. Persistence of hyperglycemia in some dogs after hypophysectomy is associated with less effective suppression of glucose production and with a very low glucose clearance.
Impairment of Insulin-mediated Glucose Metabolism by Hyperosmolality in Man
Authors: Bratusch-Marrain Paul R , DeFronzo Ralph A 
Published: September 2013

The deterioration of glucose tolerance and insulin resistance observed in states of hypertonie dehydration are commonly ascribed to a concomitant increase in circulating insulin counterregulatory hormones. To examine the effect of hyperosmolality per se on carbohydrate metabolism, tissue sensitivity to insulin was assessed by means of the euglycemic insulin clamp technique and simultaneous 3H-3-glucose kinetic analysis. Eight healthy volunteers participated in three protocols: (1) In the hyperosmolal study, serum osmolality was raised from 280 ± 1 to 302 ± 1 mosm/kg by a primed continuous infusion of hypertonie mannitol. Following 2 h of hypertonicity, a euglycemic insulin clamp study was performed. The plasma insulin concentration was acutely raised and maintained at 147 ± 20 μU/ml, while plasma glucose was maintained at basal levels; (2) In the control insulin clamp study, isotonic sodium chloride was infused instead of mannitol. No significant change in serum osmolality was observed during the control study; (3) To examine the effect of mannitol per se on insulin-mediated glucose metabolism, isotonic mannitol was infused in a third study to raise the plasma mannitol level to a similar extent as observed during the infusion of hypertonie mannitol. The serum tonicity did not change during the isotonic mannitol infusion.
Insulin-mediated glucose utilization (M) was 6.69 ± 0.51 mg/kg · min in the control study and decreased to 5.84 ± 0.40 mg/kg · min following the exposure to hyperosmolality (P &lt; 0.05). When glucose uptake by the body was expressed per unit of plasma insulin (M/l ratio), the decrement in insulin-mediated glucose metabolism by hyperosmolality was 22% (5.56 ± 0.60 versus 4.30 ± 0.43 mg/kg · min per μM/ml × 100). This could not be accounted for by changes in the plasma levels of cortisol, growth hormone, or catecholamines. Basal hepatic glucose production (1.85 ± 0.08 mg/kg · min) as well as the degree of its suppression following hyperinsulinemia (95 ± 3%) were unchanged during hyperosmolality (1.84 ± 0.08 mg/kg · min and 94 ± 2%, respectively). The infusion of isotonic mannitol had no effect on insulin-mediated glucose metabolism or suppression of hepatic glucose production by insulin.
We conclude that moderate elevations in serum osmolality, less than 10%, cause a significant decrease in insulin-mediated glucose metabolism. Thus, hyperosmolality observed following severe dehydration should be regarded as an additional factor contributing to the development of insulin resistance. This pathophysiologic concept may be of particular relevance to diabetics with severe derangements of metabolic control. Our findings underline the importance of proper rehydration in restoring to normal insulin's action on intermediary metabolism in patients who present with hyperosmolality.
Fibrinolytic Activity, Autonomic Neuropathy, and Circulation in Diabetes Mellitus
Authors: Almér Lars-Olof , Sundkvist Göran , Lilja Bo 
Published: September 2013

In diabetes mellitus the vascular endothelium often produces and releases abnormally low amounts of plasminogen activator, leading to an impaired fibrinolytic system, which might be of importance for the development of angiopathy.
In this study tests of autonomic neuropathy (AN) were performed on diabetics without autonomic symptoms. It was discovered that diabetics without AN had a significantly lower mean fibrinolytic response to stimulation than nondiabetic controls, whereas this reduction was not found in those with AN. The suggestion that asymptomatic AN might induce a normalization of the impaired fibrinolytic system in diabetes, and thus have a modifying effect on the rate of development of angiopathy, requires further study to be properly evaluated.
Binding of Insulin by Monkey and Pig Hypothalamus
Authors: Landau Bernard R , Takaoka Yoshiro , Abrams Marc A , Genuth Saul M , van Houten Mark , Posner Barry I , White Robert J , Ohgaku Seiji , Horvat Agnes , Hemmelgarn Edward 
Published: September 2013

Membrane preparations from monkey and pig hypothalami bound [125]insulin specifically. The binding appeared to be greater by preparations from anterior than posterior portions of the pig hypothalamus. Binding was time dependent, and its dissociation was first order with a half-time at 22°C of 14 min. Desalanine insulin was as effective as native insulin in inhibiting the binding of [125I]insulin, while proinsulin was less effective and desoctapeptide insulin still less effective in accord with their biologic activities. Binding by membranes from cortex and thalamus appeared to be less than from hypothalamus.
[125I]lnsulin was infused into an arterial split monkey brain preparation to determine if insulin that was blood borne bound specifically to the primate hypothalamus. Half the brain was perfused with [125I]insulin alone and the other half with [125I]insulin plus an excess of unlabeled insulin. Radioautography showed specific binding of insulin localized to the median eminence, infundibular nucleus, and microvessels.
Thus, the monkey and pig hypothalami bind insulin with characteristics similar to those reported for known target tissues for insulin. Furthermore, insulin from the blood stream binds to specific anatomical structures in the hypothalamus of the monkey.
Fetal and Neonatal Metabolism in the Pup of a Canine Diabetic Mother: Fasting Circulating Fuels and Neonatal Glucose Turnover
Authors: Kliegman R M , Miettinen E L , Tserng K Y 
Published: September 2013

The metabolic effects of previously induced alloxan diabetes were investigated among fasted newborn dogs during the first day of life. Maternal insulin-dependent diabetes resulted in enhanced maternal and fetal blood glucose and ketone bodies, while postnatal levels of these substrates were not altered. Plasma insulin levels were augmented in the fetus and neonate (3 and 6 h of age) of the diabetic mother, while pancreatic insulin content was also enhanced at fetal and 3 h of age. Circulating free fatty acid levels were diminished among pups born to diabetic mothers (IDM pups) at 3 and 6 h of age, while glycerol levels were unaffected. Nevertheless, plasma triglyceride concentrations were elevated in pups of diabetic mothers during fetal and at 3 and 6 h of newborn fasting. Systemic glucose turnover was not altered in pups of diabetic mothers at 3, 9, or 24 h, while at 6 h, glucose turnover appeared enhanced in IDM pups, which was due in part to a decline of glucose production between 3 and 6 h among controls. Gluconeogenesis was attenuated at 9 h of age among IDM pups, but increased by 24 h of age.
Hyperinsulinism in the presence of unaltered glucose turnover with attenuated free fatty acid levels suggest that neonatal canine glucose production from hepatic glycogen is less sensitive to insulin's effect than is the lipolysis-lipid reesterification cycle. Gluconeogenesis from lactate may be unnecessary if glycogenolysis is able to support systemic and hepatic substrate requirements, while insulin mediated lipid synthesis may augment tissue triglyceride deposits.
Fetal and Neonatal Metabolism in the Pup of a Canine Diabetic Mother: Hepatic Intermediary Metabolism
Authors: Kliegman R M , Miettinen E L 
Published: September 2013

The intrahepatic metabolic profile of pups from a diabetic canine pregnancy (IDM pups) was examined at birth and during the postnatal adaptation to 3, 6, 9 or 24 h of neonatal fasting. Hepatic intermediates of the glycogen, glycolytic, and Krebs cycles were determined in addition to hepatic adenine nucleotides and hepatic and muscle triglyceride concentrations. Maternal canine diabetes enhanced fetal hepatic and muscle glycogen and triglyceride content. After birth, neonatal hepatic glycogen content declined among control and IDM pups but glycogen content remained enhanced in the IDM pups at 3 and 6 h. Muscle glycogen also declined in both groups; however, it remained higher in the IDM at 3, 6, and 9 h. Muscle and hepatic triglyceride content increased in both groups. Postnatal intracellular triglyceride content was augmented in muscle tissue of the IDM at 3, 6, and 9 h while hepatic tissue from IDM had increased triglycerides at 24 h of age. Glycolytic intermediates demonstrated alterations following maternal diabetes as fructose 1, 6, diphosphate was lower in IDM pups during fetal life and at 3, 9, and 24 h while pyruvate and oxaloacetate concentrations were augmented throughout the study period when compared with age-matched controls.
Hepatic amino acids demonstrated elevated alanine concentrations in IDM pup at 6, 9, and 24 h while aspartate levels were augmented during fetal and at 6, 9, and 24 h of neonatal fasting.
These data suggest that hepatic glycogen synthesis is augmented in the fetus of the diabetic canine mother. After birth postnatal glycogenolysis is not altered and may support hepatic and systemic oxidative metabolism. Furthermore, these large tissue stores of glucose may contribute to hepatic or muscle triglyceride synthesis in addition to hepatic amino acid accumulation. The alterations of FDP, pyruvate, and oxaloacetic acid suggests that glycolysis is enhanced among pups following a diabetic pregnancy while intraheptic gluconeogenesis may be attenuated.
The Effect of Pancreatic Islet Transplantation and Insulin Therapy on Experimental Diabetic Autonomic Neuropathy
Authors: Schmidt Robert E , Plurad Santiago B , Olack Barbara J , Scharp David W 
Published: September 2013

Rats with chronic streptozotocin (SZ) diabetes develop dilatation of the alimentary tract, loss of fecal consistency, and autonomic neuropathy involving unmyelinated axons of the extrinsic innervation of the small bowel. Diabetic autonomic neuropathy involving the ileal mesenteric nerves is characterized by modest to marked dilatation of axons by distinctive subcellular organelles identical to those described in experimental and clinical axonal dystrophies. Axonopathy is confined to the alimentary tract; examination of myelinated and unmyelinated axons of the sciatic (midthigh level) and distal somatic nerves of the tail of diabetic animals with prominent ileal axonopathy failed to demonstrate significant numbers of dystrophic axons.
The prevention or reversal of diabetic autonomic neuropathy by a variety of experimental manipulations clearly indicates that the lesions we have demonstrated in chronically SZ-induced diabetic animals were produced by diabetes and were not the result of a direct neurotoxic effect of the diabetogenic agent streptozotocin. Animals did not develop axonopathy after simultaneous administration of SZ and nicotinamide, a procedure which prevents pancreatic beta-cell necrosis and induction of diabetes while exposing the nervous system to a possible neurotoxic agent. Selected animals that were given SZ, became diabetic, and subsequently received daily insulin therapy or pancreatic islet transplantation also did not develop axonopathy. Transplantation of pancreatic islets 6 mo after induction of diabetes, a time at which mesenteric axonopathy was well developed, quickly reestablished normoglycemia, and within 3 mo resulted in nearly complete resolution of the neuropathy. Mild chronic diabetes maintained for 5–6 mo failed to produce significant levels of axonopathy. Diabetes-induced alteration in the gross appearance and weight of portions of the digestive tract and stool consistency were completely or partially prevented by institution of diabetic control.
Muscle Capillary Basement Membrane in Identical Twins Discordant for Insulin-dependent Diabetes
Authors: Barnett A H , Spiliopoulos A J , Pyke D A , Stubbs W A , Rowold E , Hoffmann P , Faller A , Kilo C , Miller J P , Williamson J R 
Published: September 2013

Although hereditary factors clearly modulate susceptibility to develop diabetes, their role as determinants of vascular complications associated with diabetes remains unclear. These studies were undertaken to further assess the extent to which capillary basement membrane thickening (CBMT) is governed by metabolic derangements associated with relative or absolute insulin deficiency versus genetic determinants of vascular disease closely linked to but independent of those modulating susceptibility to develop relative or absolute insulin deficiency. Quadriceps muscle capillary basement membranes obtained by needle biopsy were examined in eight pairs of identical twins discordant for insulin-dependent diabetes (IOD) for 11–29 yr. Biopsy material from one of the diabetic twins was technically unsuitable for study.
The average CBM width of the IDD twins was found to be significantly thicker than that of their nondiabetic (ND) twin mates (t = 2.50, P &lt; 0.025). Three IDD, but none of the ND twins, had basement membrane width values in excess of 95% upper tolerance intervals for age- and sex-matched controls with no family history of diabetes.
The absence of CBMT in all of the ND twins and in four of the IDD twins with diabetes of 15–24 yr duration argues against the existence, in this group of subjects, of hereditary determinants of diabetic vascular disease linked to those governing susceptibility to develop diabetes. In addition, the absence of CBMT in four subjects with IDD of 15–24 yr duration is consistent with evidence from other studies indicating that diabetic microangiopathy is not an inevitable consequence of the diabetic milieu. The finding that muscle CBMT and retinopathy were restricted to IDD twins attests to the importance of the diabetic milieu as a predisposing or permissive factor in the initiation and progression of diabetic vascular disease.
Lower Levels of Erythrocyte Membrane Fluidity in Diabetic Patients: A Spin Label Study
Authors: Kamada Tetsuro , Otsuji Shogo 
Published: September 2013

The dynamic properties of intact erythrocyte membrane in diabetic patients were investigated by means of electron spin resonance using three stearic acid spin labels (SAL): 5-, 12-, and 16-SAL. Significantly lower levels of erythrocyte membrane fluidity were revealed with 16-SAL as a probe in diabetic patients when compared with normal controls. However, there were no significant differences in fluidity values using 5- or 12-SAL between the two groups. Therefore, it became obvious that the decrease in fluidity was located in deeper sites (hydrophobic region) of the erythrocyte double membrane in diabetic patients. It was strongly suggested that changes in the membrane cholesterol to phospholipid molar ratios are not a principal factor contributing to the fluidity change. A significant increase of sphingomyelin and decrease of phosphatidylethanolamine were found in the erythrocyte membrane of diabetic patients and an alteration in membrane phospholipidclasses and their acyl-chains could conceivably be related to the fluidity change.
There were no significant correlations betweenchange in membrane fluidity and most plasma lipids, plasma lecithin-cholesterol acyl-transferase activities erythrocyte glycosylated hemoglobin, erythrocyte adenosine triphosphate, fasting blood glucose or duration of the disease. Plasma cholesterol of high-density lipoprotein showed a significant negative correlation with the membrane fluidity values.
Some of the possible factors contributing to and the significance of the lower levels of erythrocyte membrane fluidity were discussed in conjunction with both metabolic and clinical aspects in diabetic patients.