bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous Diabetes in Macaca Nigra
Authors: Howard Charles F
Published: December 2014

In a closed breeding colony of Macaca nigra (black Celebes apes) there was a marked proclivity for a spontaneous diabetic-like state closely analogous to human diabetes. Numerous diabetic signs were present, including abnormal intravenous and oral glucose tolerance tests, hyperglycemia, impaired insulin response, hypertriglyceridemia, increased prebetalipoprotein, retinal vascular aberrations, abnormalities in the islets of Langerhans, and pronounced weight loss in a few severely diabetic monkeys. A classification of diabetic status established primarily on deviation of the intravenous glucose tolerance test from results in normal Celebes apes places over 50 per cent of these interrelated monkeys in nonnormal categories.
Glucose Metabolism and Responsiveness to Bovine Insulin by Adipose Tissue from Three Mammalian Species
Authors: Di Girolamo Mario , Mendlinger Sheldon
Published: December 2014

The rate and pattern of glucose metabolism by slices of epididymal adipose tissue from ad libitum-fed rats, hamsters and guinea pigs were studied in an in vitro incubation, at three stages of development during the first year of the animals' lives. The results were expressed on the basis of fat cell number and in relation to the fat cell size. The responsiveness of the adipose cells to the glucose-transport stimulating effect of bovine insulin was determined in relation to the age of the animals and to the adipocyte volume. The data indicate that the amounts of basal glucose metabolized to [CO2 + triglyceride] per fat cell remained relatively constant in each of the three species, even though the fat cell volumes varied markedly. In concomitance with fat cell enlargement, the pattern of glucose metabolism exhibited a progressive change, with reduction in the proportions of glucose converted to CO2 and glyceride-fatty acid and a significant increase in that of glucose converted to glyceride-glycerol.

The effect of bovine insulin in stimulating glucose transport and metabolism varied from species to species being greatest in the rat and smallest in the guinea pig fat cells. In each species, the magnitude of the response to bovine insulin was found to be decreased as the fat cells enlarged with age and ad libitum feeding of the animals. The guinea pig differed from the other two species in the limited capacity of the fat cells to enlarge during the period of observations. In spite of the small fat cell size, the response of guinea pig fat cells to bovine insulin was minimal. During growth and development of the animals, fat cell number, baseline rate of glucose metabolism and responsiveness to insulin contribute to the over-all glucose metabolism by the epididymal fat pads; in the guinea pig, the contribution of fat cell number appeared to be quantitatively more important than the stimulatory effect of insulin.
Effect of Blood Sugar Control on the Accumulation of Sorbitol and Fructose in Nervous Tissues
Authors: Ward J D , Baker R W R , Davis Barbara H
Published: December 2014

Some products of the sorbitol metabolic pathway of glucose were extracted from peripheral nerves and spinal cords of rats, identified, and measured. Within a few days after a diabetic state was induced with streptozotocin, glucose, sorbitol, and fructose in nerve and cord had risen sharply as blood glucose increased. These levels were partially controlled when the blood sugar was restricted by insulin, but they increased rapidly when the insulin was withheld. Withdrawal of treatment resulted in a much greater rise of the fructose in the nervous system in animals that had been diabetic for six weeks before institution of treatment with insulin than in animals treated from induction. When phen-formin was used as a controlling agent in place of insulin, accumulation of glucose and fructose in the nervous system was enhanced, whereas fructose was found to decrease when tolbutamide was used.

Earlier workers have shown that the sorbitol pathway seems to be associated with the Schwann cell and that dysfunction of this cell leads to segmental demyelination. We find that accumulation in nerves of the products of the sorbitol pathway may be minimized when blood sugar is controlled; since we have evidence that in human beings with diabetes good control improves the state of myelination of already damaged nerves, it is postulated that herein lies the mechanism whereby control of diabetes is likely to lead to a reduction in the incidence of nerve damage.
Disseminated Intravascular Coagulation in Diabetes Mellitus, with Reference to the Role of Increased Platelet Aggregation
Authors: Kwaan Hau C , Colwell John A , Suwanwela Nibha
Published: December 2014

A state of hypercoagulability associated with changes in the clotting factors and platelet function has been postulated to be important in the increased thrombotic complications in diabetes mellitus. A fifty-nine-year-old man was admitted with severe diabetic ketoacidosis and shock. Shortly after restoration of his gross fluid and electrolyte imbalance, he developed extensive bleeding into his lungs and gastrointestinal tract. His serum was grossly lactescent. His blood was incoagulable. The existence of disseminated intravascular coagulation was indicated by a decrease in the platelet count and in the levels of fibrinogen, plasminogen, and Factors V and VIII. Plasminogen activator, plasmin, and fibrinogen degradation products all were increased in the plasma, as were cholesterol, triglycerides, phospholipids, total lipids, and free fatty acid concentrations. Postmortem examination revealed widespread hemorrhages. Microthrombi characteristic of platelet aggregates were present in his lungs and kidneys. Serial dilutions of his lipidemic plasma up to 1:150 resulted in increased ADP-induced aggregation of normal platelets. We postulate that the strong influence of the patient's plasma on platelet aggregation was the initial event leading to his disseminated intravascular coagulation. The finding of a platelet aggregation-enhancing factor in other diabetic subjects may shed light on the mechanism of thrombogenesis in diabetes.
Counter-Regulation of Basal Insulin Secretion During Alcohol Hypoglycemia in Diabetic and Normal Subjects
Authors: Bagdade John D , Bierman Edwin L , Porte Daniel
Published: December 2014

To determine (1) whether differences in insulin levels, and (2) the presence of diabetes mellitus influenced the hypoglycemie response to alcohol, immunoreactive insulin (IRI) and glucose levels were measured during alcohol infusion in twenty obese and thin subjects with normal and mildly abnormal carbohydrate tolerance after a preparatory three-day fast. Despite small differences in the rates of decline of glucose, IRI fell promptly, and were indistinguishable when the subjects were grouped according to both glucose tolerance and weight. These findings indicate that the regulation of basal IRI in response to a falling glucose level during ethanol hypoglycemia appears to be intact in both obesity and mild diabetes.
Effect of Insulin Deficiency on Hepatic Ribosomal Aggregation
Authors: Tragl Karl H , Reaven Gerald M
Published: December 2014

Ribosomes were isolated from liver homogenates of normal and alloxan diabetic rats. Sedimentation of these ribosomes through a continuous sucrose gradient indicated that insulin deficiency was associated with an increase in the proportion of ribosomes existing as the 80 S monomer. In a second series of experiments ribosomes from diabetic animals were also shown to bind more avidly to 3H-polyuridylic acid (polyU). When hepatic ribosomes from normal and diabetic rats were incubated for forty-five minutes at 37° C. in a complete amino acid-incorporating system they underwent essentially total disaggregation into single ribosomes, and the previously noted difference between normal and diabetic ribosome binding to polyU was abolished. The sedimentation characteristics of ribosomes from normal and diabetic rats indicate that insulin deficiency results in an increase in the proportion of ribosomes free of mRNA, and, since they are free of mRNA, a greater than normal proportion of ribosomes from diabetic animals are capable of complexing with polyU. Obviously, producing equal numbers of monosomes by prior incubation in an amino acid-incorporating system would be expected to obliterate the difference in polyU binding between ribosomes from normal and diabetic animals. Thus, both lines of experimental evidence are consistent with the hypothesis that insulin deficiency produces a disaggregation of hepatic poly-somes, leading to an increase in the proportion of ribosomes that are not bound to mRNA.
The Insulin Receptor
Authors: Cuatrecasas Pedro
Published: December 2014

Studies with bulky and insoluble insulin derivatives indicate that this hormone can activate various metabolic processes by interaction with cell surface structures. A definition of “receptor” is offered which is operationally useful in studies directed to the identification and purification of receptor structures. Studies are described which measure the specific binding of insulin to intact fat cells and liver and fat cell membranes. The properties of these interactions and the correlation with metabolic events indicate that biologically significant receptors are being studied. The possible contribution of membrane carbohydrates, proteins and lipids to the environment and function of the receptor is considered. Studies pertinent to the extraction and purification of the insulin receptor are discussed.
The Prediabetic State, Its Nature and Consequences—A Look Toward the Future
Authors: Cerasi Erol , Luft Rolf
Published: December 2014

The prediabetic state is characterized by normal glucose tolerance but decreased insulin secretion following glucose stimulation. In spite of our earlier beliefs, this state is not always devoid of metabolic consequences. Thus, the disappearance rate of intravenously administered glucose (k-value), although within the normal range, is significantly lower than in the control group. In a few prediabetics the regulation of hepatic glucose output resembles that of diabetics. In some, the lipolytic response to physical exercise is increased to the extent found in manifest diabetes. Furthermore, prediabetic mothers may give birth to children with diabetic fetopathy. Many of the newborns of these women show high k-values as do children of diabetic women.

The decreased insulin output of prediabetics and mild diabetics is probably due to a decreased sensitivity for glucose of a specific receptor of the beta cells of the pancreas. This suggestion is supported by the finding that both prediabetics and mild diabetics can release normal amounts of insulin provided blood glucose is raised to 500–1,000 mg./ 100 ml.

The transition from prediabetes to diabetes may be induced by several factors such as progressive deterioration of insulin output or addition of diabetogenic factors like obesity and overproduction of human growth hormone. Hepatic glucose output in the prediabetic is regulated with a higher than normal efficiency, thus compensating for the deficient insulin secretion. The failure of this important mechanism may be a major precipitating factor for diabetes.

The future prevention and treatment of diabetes mellitus will depend on the development of agents that (a) correct the sensitivity of the glucose receptor of the beta cells and (b) stimulate the ability of the liver to suppress its glucose output.
Effect of Submaxillary Gland Extirpation on Glucose and Insulin Tolerance in Dogs
Authors: Steinberg Terry , Passy Victor , Gwinup Grant
Published: December 2014

Serum glucose and immunoreactive insulin (IRI) responses to oral glucose and intravenous insulin tolerance tests were determined in dogs before and after total bilateral extirpation of their submaxillary glands. A comparison was made with a control group of dogs before and after sham operations. Postoperative studies were performed at one, three and six months after surgery. No significant differences in glucose and IRI responses were observed between the two groups of dogs, nor upon comparison of the responses within each group at the various periods studied.

A review of the literature which relates the salivary glands to diabetes mellitus in both experimental and clinical studies is presented. Our own experience of diabetes mellitus with apparent salivary gland involvement is briefly discussed.

It is concluded that despite the relatively frequent association of salivary gland involvement and diabetes mellitus, the role of these glands in the pathogenesis and management of diabetes mellitus is obscure. At this time there is no apparent rationale to the performance of total submaxillary gland extirpation for the treatment of diabetes mellitus.
Incorporation of SE75 Selenomethionine into a Protein Component of Plasma Very-Low-Density Lipoprotein in Man
Authors: Eaton R Philip , Kipnis David M
Published: December 2014

This investigation is designed to examine the intravascular kinetic behavior of apoprotein associated with the very-low-density lipoproteins (VLDL) in man. The incorporation of intravenously injected selenomethionine Se-75 into plasma proteins was examined in ten subjects. A component of the apoprotein associated with the VLDL was isolated by solvent extraction, and was found to have a uniquely short intravascular half-life of one hour, resulting in a plasma flux of 281 mg./day with only 15.3 mg. circulating in the plasma. In patients with abnormal lipemia, this protein was found to have a prolonged intravascular half-life, and an increased intravascular flux of 979 mg./day. This threefold rise in flux was accompanied by an anticipated increased plasma concentration of the isolated protein to levels ranging from 25 to 750 μg./ml., representing a marked rise from the normal plasma concentrations of 4.8 ± 2.9 μg./ml. The data are interpreted as demonstrating a distinct abnormality in the kinetic behavior of Se-75-labeled protein isolated from VLDL from patients with endogenous lipemia.
Insulitis (Lymphocytic Infiltration of Pancreatic Islets) in Late-onset Diabetes
Authors: LeCompte Philip M , Legg Merle A
Published: December 2014

Two examples of “insulitis” (infiltration of pancreatic islets by mononuclear cells, apparently chiefly lymphocytes) are reported in adults with late-onset diabetes. Attempts to demonstrate cell-bound antibodies by immunofluorescent methods and to isolate a virus in one case were inconclusive. Possible implications with regard to auto-immune processes and virus infection in the etiology of diabetes are discussed.
Effect of Mannose, Fructose and Hydroxybutyrate on the Hepatic Response to Hypoglycemia
Authors: Hetenyi G
Published: December 2014

In normal nonanesthetized dogs the increased endogenous (hepatic) glucose production in insulin-induced hypoglycemia is suppressed by the infusion of D-mannose but not of D-fructose. This compensatory increase in glucose production during insulin-induced hypoglycemia is somewhat diminished but still present in dogs fasted for eight days. In fasted dogs, but not in dogs in the post-absorptive state, the infusion of DL-β-OH-butyrate is able to diminish but not to suppress this compensatory increase in glucose production. The results suggest that it is the availability of substrate to the brain rather than to the liver that sets into motion the mechanism that ultimately is responsible for the increase of glucose production, although the mechanism of the effect of β-OH-butyrate appears to be somewhat uncertain.
Response of Peripheral Blood Lymphocytes from Patients with Diabetes Mellitus to Phytohemagglutinin and Candida Albicans Antigen
Authors: Ragab Abdelsalam H , Hazlett Barbara , Cowan Donald H
Published: December 2014

Cells from the peripheral blood of twenty-three patients with diabetes mellitus were tested to determine their response to phytohemagglutinin (PHA) and Candida albicans antigen. The response was not significantly different from that of cells from normal subjects.
Hypophysectomy for Diabetic Retinopathy During Pregnancy
Authors: Martin F I R , Taft P
Published: December 2014

A clinical account is given of a patient with diabetes for twenty-one years, suffering from proliferative diabetic retinopathy, in whom hypophysectomy was performed in the eighth week of pregnancy. The pregnancy proceeded uneventfully, apart from the development of hydramnios; the patient was delivered at the thirty-seventh week by cesarean section. Regression of the retinopathy was noted to commence during the pregnancy and has continued since delivery. Insulin requirements increased by 30 per cent during pregnancy. The baby showed none of the features commonly seen in the infants of diabetic mothers.
Characterization of Glucose Metabolism in the Isolated Rat Heart During Fetal and Early Neonatal Development
Authors: Clark Charles M
Published: December 2014

Uptake of 1-14-C glucose, lactate production, 14-C-CO2 production, glycogen content, and the incorporation of 1-14-C glucose into glycogen, protein, and lipid have been studied in isolated fetal and neonatal rat hearts from the sixteenth day of gestation to the fifth neonatal day. The effects of insulin (5,000 μU./ml.) on these processes was also studied.

Glucose uptake fell during gestation from 28.4 ± 2.2 to 10.0 ± 1.1 μmoles per gram wet weight tissue per two hours and remained constant after birth. At all ages insulin significantly increased glucose uptake. Lactate production Fell from 77.6 ± 11.5 to 51.5 ± 2.3 μmoles per gram wet weight per two hours between the sixteenth day of gestation and the first day after birth and was not influenced by insulin. Production of 14-C-CO2 from glucose was small (range: 2 to 7 per cent of glucose uptake) and was also unaffected by insulin. Hot KOH extractable cardiac glycogen content rose between the sixteenth and twenty-first day and then fell. The change in hot KOH extractable cardiac glycop; en followed similar changes in 1-14-C glucose incorporation into glycogen. Whereas 1-14-C glucose incorporation into tiot KOH extractable glycogen was unaltered by insulin until after birth, insulin did significantly augment the incorporation of 1-14-C glucose into the cold TCA extractable fraction. This fraction, which includes oligosaccharides destroyed by the hot KOH, also had a higher specific activity than the hot KOH extractable glycogen. The majority of the intracellular counts were in this fraction; the remainder of the counts were in the lactate and acetate or acetoacetate fraction. Insulin did not augment incorporation of 1-14-C glucose into these fractions. Incorporation of 1-14-C glucose into both protein and lipid was less than 2 per cent of glucose uptake and was not influenced by insulin.

The data suggest that fetal myocardial development is characterized by a progressive decline in glucose uptake which can be stimulated by insulin from the sixteenth day onward. The conversion of 14-C glucose to 14-C-CO2, protein, and lipid was not influenced by insulin. Incorporation of 1-14-C glucose into hot KOH extractable glycogen was augmented by insulin only after birth under the experimental conditions described. The cold TCA extractable glycogen had a higher specific activity and insulin stimulated the incorporation of 1-14-C glucose into this fraction. It is concluded that insulin augments glucose uptake and incorporation into a glycogen fraction turning over rapidly in the fetal rat heart.
Comparison of Juvenile Diabetics with Positive and Negative Organ Specific Antibody Titers: Evidence for Genetic Heterogeneity
Authors: Nissley S Peter , Drash Allan L , Blizzard Robert M , Sperling Mark , Childs Barton
Published: December 2014

Juvenile diabetics with significant thyroid, gastric or adrenal antibody titers were compared with juvenile diabetics with negative antibody titers on the basis of various parameters of clinical and family history. Parents and siblings of juvenile diabetics with positive antibody titers have a significantly higher frequency of positive antibody titers than do parents and siblings of juvenile diabetics with negative antibody titers. This finding provides evidence for genetic heterogeneity among juvenile diabetics.
Specificity of the Chemical Alteration in the Diabetic Glomerular Basement Membrane
Authors: Beisswenger Paul J
Published: December 2014

A distinct chemical change has previously been described in the glomerular basement membrane (GBM) of patients with long standing diabetes mellitus. To assess the specificity of this lesion the chemical composition of the GBM was determined in a group of patients with nondiabetic renal disease associated with significant proteinuria and agematched normal controls. The chemical composition of the GBM in these diverse cases closely resembled that seen in controls. The increase in glucosyl-galactosyl hydroxylysine and the decrease in lysine previously described in the diabetic GBM were not observed in the nondiabetic cases. The absence of significant change in chemical composition of the GBM in nondiabetic renal disease would tend to support the hypothesis that the chemical change in the diabetic GBM is specific for the renal disease associated with long standing diabetes mellitus.
Insulin and Insulinlike Activity in Extracts of Tumors Associated with Hypoglycemia
Authors: Abbasi Ali , Power Lawrence
Published: December 2014

Insulin assays were performed on tissue extracts from ten nonpancreatic tumors and five islet-cell adenomas, all of which were associated with hypoglycemia. Acid alcohol and normal saline extractions were made from tumor tissue as well as from normal tissue. The insulin content of extracts was determined both biologically and immunologically, utilizing the rat epididymal fat pad to measure insulinlike activity (ILA) and the double antibody radioimmunoassay to estimate insulin (IRI).

All five islet-cell adenomas were found to have significant concentrations of biologically and immunologically active insulin. The nonpancreatic tumors had no significant concentration of insulin or insulinlike activity, but results were equivocal in one hepatoma. The mechanism by which such tumors induce hypoglycemia remains unknown. It does not appear to result from the elaboration of insulin or of products with insulinlike activity.
Insulin Control of Glucagon Release From Insulin-deficient Rat Islets
Authors: Buchanan K D , Mawhinney W A A
Published: December 2014

Glucagon release from isolated islets (collagenase digestion) in control and streptozotocin-treated diabetic rats was measured in varying glucose concentrations and in the presence or absence of added insulin. High glucagon release from diabetic islets was noted, and this glucagon release could not be suppressed by glucose. Incubation of diabetic islets with insulin, 1,000 μU./1 ml., suppressed glucagon release at high glucose concentrations. Addition of insulin to control islets had no effect, nor had the administration of insulin to diabetic animals before decapitation. It is concluded that insulin deficiency removes the normal glucose suppression of glucagon release and that the effect can be reversed by high concentrations of insulin.
Regulation of Rat Hexokinase Isoenzymes: I. Assay and Effect of Age, Fasting and Refeeding
Authors: Bernstein Robert S , Kipnis David M
Published: December 2014

A new and highly sensitive fluorimetric assay for hexokinase (HK) isoenzymes which requires only 5 μg. of tissue protein is described. This assay has been used to examine the alterations in the HK isoenzymes of rat skeletal muscle and adipose tissue under a variety of physiologic conditions. In both tissues, HK-II declined progressively with increasing age, reaching plateau levels in animals larger than 300 gm., whereas HK-I remained constant. HK-II activity decreased markedly in both tissues of young rats after a twenty-four to forty-eight hour fast and was restored after two days of refeeding. HK-I was not affected by the fasting-refeeding regimen. In older rats (300 gm.), adipose tissue HK-II did not fall during fasting but exhibited a significant rise when refeeding was instituted. “Pulsing” the fasted rat with periodic episodes of hyperglycemia (0.5 gm. glucose intraperitoneally every eight hours) did not prevent the fall in HK-II during fasting or restore HK-II activity in the two day fasted animal.

Approximately 50 per cent of HK-I, but little or none of HK-II, is bound to subcellular organelles in skeletal muscle. In adipose tissue, however, about one-third of the HK-II and insignificant amounts of HK-I are in the bound form. Ratios of bound to free HK are not altered during aging, but HK-II binding in adipose tissue is decreased during refeeding.

Normal mice exhibited a decrease in both adipose tissue HK isoenzymes with aging. Adipose tissue of sixteen week old obese hyperglycemic mice (obob) has lower HK-II and higher HK-I activity than that of normal litter mates, but no differences were detected in obob and normal mice at five weeks of age.

The changes in muscle and adipose tissue HK-II activity associated with aging and fasting-refeeding parallel the known changes in insulin sensitivity of these tissues under comparable conditions.
Differential Renal Protein Clearance in Diabetes
Authors: Jerums G , Post R S , Miller M , Barzellato E
Published: December 2014

Measurements of differential renal protein clearance (ratio of the renal clearance of immunoglobulin-G to that of transferrin) have been performed in long-standing diabetics with varying amounts of proteinuria. In seventy-one diabetics the IgC-transferrin clearance ratio (0.44 ± 0.04, mean ± S.E.M.) was significantly lower than in seventeen normal subjects (1.85 ± 0.24). The mean IgG-transferrin clearance ratio was significantly lower in fourteen of these diabetics with normal amounts of proteinuria than in normal subjects. A further decrease in clearance ratio was apparent when nonproteinuric (125 mg./24 hr.) and minimally proteinuric (500 mg./24 hr.) diabetics were compared. Deterioration of renal function in proteinuric diabetics was associated with an increase in the IgG-transferrin clearance ratio. The results taken overall suggest that an initial fall and a delayed rise in the clearance ratio occurs in individuals who progress to terminal renal failure. The initial fall in the IgG-transferrin clearance ratio may reflect the earliest renal changes of diabetic nephropathy. The relationship of this fall to the onset of carbohydrate intolerance remains to be clarified.
Diphenylhydantoin: Its Use in Detecting Early Insulin Secretory Defects in Patients with Mild Glucose Intolerance
Authors: Levin Seymour R , Reed James W , Ching King-Nien , Davis John W , Blum M Robert , Forsham Peter H
Published: December 2014

Diphenylhydantoin (DPH) is known to inhibit insulin secretion in vitro and can cause hyperglycemia in man. To determine if there were selective effects of this drug in diabetes, insulin responses to intravenous stimuli were measured before and after ingesting the drug for several days in seven nonobese subjects with mild oral glucose intolerance. These were compared with responses of eight nonobese control subjects with normal oral glucose tolerance.

Before DPH, early insulin release after intravenous glucose was similar in both groups, though glucose clearance was subnormal in the glucose-intolerant group. Arginine, given thirty minutes after glucose (postglucose arginine) was followed by prominent insulin release in both groups. After DPH, there was no significant alteration in glucoseinduced earlyinsulin release or clearance of glucose, though downward trends were noted in both groups. However, after DPH, the glucose-intolerant group showed significant reduction of insulin responses to postglucose arginine.

These differences in drug effect occurred despite similar serum drug levels and per cent binding of DPH in the normal and in the glucose-intolerant group. Drug levels attained were in the effective range seen in patients taking DPH for epilepsy.

In the isolated, perfused rat pancreas, effects of DPH in the presence of a high arginine stimulus were differentiated from those of a glucose stimulus. Whereas DPH eliminated both early and late arginine-induced insulin secretion, only late glucose-induced secretion was abolished by the drug.

These data suggest that DPH will unmask early defects of insulin secretion in patients with mild oral glucose intolerance. The major early effect of the drug on insulin secretion in these patients is thus seen after a nonglycemic stimulus, postglucose arginine, which may have an insulinotropic mechanism distinctive from that of glucose.
Pancreatic Islet Transplantation in the Rat
Authors: Leonard Robert J , Lazarow Arnold , Hegre Orion D
Published: December 2014

Twenty to thirty-five neonatal rat pancreases (2.5 to 4.5 days postpartum) were minced, dissociated in a collagenasetrypsin-EDTA solution, washed, centrifuged, resuspended in Tyrode's solution, and transplanted intraperitoneally to an alloxan-diabetic recipient. All of eight highly inbred moderate-diabetic rats (mean pretransplant blood sugar level and daily urine glucose excretion = 340 mg./100 ml. and 6.0 gm., respectively), showed a reversal of the diabetes within several days following isotransplantation (blood sugar and daily urine glucose excretion levels dropped to less than 150 mg./100 ml. and 0.1 gm., respectively). Two of seven highly inbred severe-diabetic rats (mean pretransplant blood sugar level and daily urine glucose excretion = 440 mg./100 ml. and 8.0 gm., respectively), recovered from their diabetes about two weeks following isotransplantation. In these highly inbred recipients which recovered from their diabetes, normoglycemia has persisted for more than five months. Control animals receiving liver transplants showed no significant changes in their diabetes. Exploration of the peritoneal cavity, after two months of remission, demonstrated isolated implants in association with the liver, spleen, pancreas, abdominal wall, etc. Yascularized grafts consisted primarily of cords of heavily granulated (aldehyde fuchsin positive) beta cells. Acinar cells were not identified. By contrast, the recipient pancreas showed few identifiable beta cells (characteristic of alloxan diabetes), but these were heavily granulated, presumably because of the controlled diabetic state. In some grafts, removed several days following implantation, mitotic figures were seen in cells containing aldehyde fuchsin positve granules. Similar homotransplants were carried out in thirty-seven partially inbred moderate-diabetic recipients; 46 per cent showed a transitory recovery from their diabetes lasting three to thirteen days. However, the pretransplant diabetes was re-established in one to three weeks and this was attributed to the rejection of the transplant. These studies indicate that dissociated neonatal pancreas forms functional islet implants capable of reversing diabetes in alloxanized rats.
Fetal Rat Pancreas: Differentiation of the Islet Cell Component in Vivo and in Vitro
Authors: Hegre Orion D , McEvoy Robert C , Bachelder Vesta , Lazarow Arnold
Published: December 2014

Fetal rat pancreases, Day 16 through Day 22 postcoitum, were analyzed by immunoassay for insulin to assess islet cell development in vivo. The rise in pancreatic insulin concentration observed during gestation was relatively constant, amounting to 50 to 100 per cent per day, and was accompanied by increases in the total islet mass of the pancreas.

A difference was found in the potential of the pancreas for islet differentiation in organ culture which was related to the developmental state of the pancreas at the time of explantation. Highly differentiated islets of twenty-two day fetal pancreas were maintained in organ culture, while large increases in the islet mass occurred following organ culture of relatively undifferentiated eighteen day fetal pancreas.

Using the present organ culture system, explants can be produced which are composed of 25 per cent islet cells and contain 17 mU. of insulin activity per milligram.
Abnormal Serum Growth Hormone Response to Exercise in Maturity-onset Diabetics
Authors: Hansen Aage Prange
Published: December 2014

Serum growth hormone was studied during a mild exercise load of 350 kgm. per minute for twenty minutes in four groups of subjects: nonobese normal subjects, obese normal subjects, nonobese maturity-onset diabetics and obese maturity-onset diabetics.

It was found that (1) the fasting pre-exercise serum growth hormone level was higher and the exercise response occurred earlier and was greater in diabetics than in normal subjects; (2) in the nonobese groups, the basal values and exercise responses in diabetics were significantly different from those of normal individuals. In the obese groups, the mean exercise response was higher in diabetics than in normals, but this difference was not significant; the basal values were identical in the two groups; and (3) the basal values and exercise responses were higher in nonobese diabetics than in obese diabetics. In normal subjects, the exercise responses were higher in the nonobese group than in the obese group.
Human Growth Hormone Secretion after Double Stimulation with Arginine in Normal and Insulin-dependent Diabetic Women
Authors: Koncz Lajos , Soeldner J Stuart , Balodimos Marios C , Boden Guenther , Gleason Ray E , Younger Donna
Published: December 2014

The standard intravenous arginine test was modified by infusing two equal doses of arginine eighty minutes apart. The serum growth hormone, blood glucose and plasma free fatty acid responses were studied in fifteen young juvenileonset diabetic women and in seven healthy women of comparable age and weight. The biphasic growth hormone response to the two arginine infusions observed in normals did not occur in the diabetics. In addition, the diabetics differed from the normals in several qualitative aspects of growth hormone secretion. A derangement in the diabetic is postulated with impaired sensitivity or defective mechanism of growth hormone secretion. Diabetics with chronically elevated blood glucose levels had a blunted growth hormone response to arginine. In five patients with diabetic retinopathy, growth hormone response was somewhat blunted, probably due to higher blood glucose levels, as compared with findings in five patients without this complication.
Increased Kidney Size and Glomerular Filtration Rate in Early Juvenile Diabetes
Authors: Mogensen C E , Andersen M J F
Published: December 2014

Glomerular filtration rate (GFR), renal plasma flow (RPF) and roentgeno graphic kidney size were measured in twelve normal young male subjects and in twelve juvenile diabetics with a mean duration of diabetes of 4.9 years. GFR but not RPF was significantly elevated in the diabetics. Furthermore, calculated kidney weight corrected to 1.73 m.2. body surface was increased in the diabetics, being 391 gm. ± 46.2 (S.D.) [normal value 321 gm. ±54.6 (S.D.) (p < 0.01)]. When GFR was expressed per gram calculated kidney weight practically identical values were found in normals and diabetics. Moreover, there was a clear positive correlation between GFR, RPF and kidney size in both normals and diabetics (p < 0.01 in all cases). There was no statistically significant change in RPF per gram calculated kidney weight. These results suggest that there is a basal connection between enlarged kidneys and theelevated GFR of early diabetes.
Neuromuscular Junction Defect in Diabetes
Authors: Miglietta Osvaldo
Published: December 2014

Neuromuscular transmission has been studied electromyographically in thirty diabeticpatients. The median nerve was stimulated rapramaximally at the wrist, and the evoked electrical response of the abductor pollicis brevis was recorded on a cathode ray oscilloscope. Pulse trainsof twenty to twenty-four stimuli were used in frequency varying from 2 to 500 per second.

In all patients the twitch rate of nerve stimulation was well maintained. Tetanic stimulation, however, was poorly sustained. A progressive decrement of the action potential amplitude occurred rapidly and earlier in many patients at frequencies that facilitated or left unchanged the amplitude in normal subjects. The drop in amplitude was particularly evident with trains of 50 and 100 per second.

He easy fatigability of neuromuscular transmission was present in clinically not involved nerve and muscle and could represent an early and only evidence of neuronal failure in diabetic patients.
Apolipoprotein B Levels and Altered Lipoprotein Composition in Diabetes
Authors: Schonfeld Gustav , Birge Clifford , Miller J Philip , Kessler Gerald , Santiago Julio
Published: December 2014

Hyperlipoproteinemia is found in only 25 to 50 per cent of persons with diabetes. However, carbohydrate, lipid and lipoprotein metabolism are so closely related that one would expect some alterations in lipoprotein metabolism in nearly all diabetic subjects. We wondered whether the metabolism of lipoproteins in normoUpemic diabetic patients was normal and whether the metabolism of lipoproteins in subjects with hyperlipoproteinemia and diabetes differed from those without diabetes. As a first approach to these questions, the levels of lipoprotein lipids and apoUpoproteins were determined in ninety-seven diabetics and seventy-two nondiabetics, and lipoprotein compositions were computed. Among those with diabetes, seventy-one were normoUpemic—twelve were type Ila and fourteen were type IV. In each of the diabetic groups, low density and high density lipoproteins were enriched in triglyceride (p < 0.01). These alterations in lipoprotein composition were not accounted for by differences in treatment modality, sex, race, age, or ponderal index. Thus the presence of diabetes itself appears to result in altered low and high density lipoprotein compositions. The mechanism(s) for the changes in the high density lipoproteins is (are) unknown, but in light of present knowledge the presence of triglyceride-enriched LDL could mean that a less dense moiety of low density lipoproteins may be accumulating in diabetic plasma, and this could result from altered rates of turnover of ApoB containing lipoproteins. Of course appropriate studies are needed to confirm this formulation.
Streptozotocin Resistance of the Genetically Diabetic KK Mouse
Authors: Iwatsuka Hisashi , Shino Ako , Taketomi Shigehisa
Published: December 2014

Intraperitoneally administered streptozotocin (100 mg. per kilogram) produced hyperglycemia (higher than 200 mg. per 100 ml.) in 100 per cent of C57BL, but in none of KK mice. Pretreat-ment with phentolamine (50 mg. per kilogram), an α-adrenergic blocking agent, decreased resistance of KK mice to the diabetogenic action of streptozotocin. On the other hand, pre-treatment with propranolol (10 mg. per kilogram), a β-adrenergic blocking agent, induced resistance to streptozotocin in C57BL mice. This effect of propranolol was potentiated by administration of epinephrine (1 mg. per kilogram).

These findings suggest that the α-adrenergic system protects pancreatic β cells from cytotoxic action by streptozotocin, indicating a predominance of the α-adrenergic system in diabetic mice of the KK strain.
Inhibition of Pancreatic Glucagon Responses to Arginine by Somatostatin in Normal Man and in Insulin-Dependent Diabetics
Authors: Gerich John E , Lorenzi Mara , Schneider Victor , Kwan Chuk W , Karam John H , Guillemin Roger , Forsham Peter H
Published: December 2014

Somatostatin, a recently synthesized hypothalamic peptide thought to represent growth hormone-release-inhibiting factor, has been previously shown to inhibit pancreatic glucagon secretion in species other than man. To determine whether somatostatin also inhibits human glucagon secretion, plasma glucagon responses during intravenous infusion of arginine alone (250 mg. per kilogram over twenty-five minutes) and in combination with synthetic cyclic somatostatin (20,μg. per minute) were compared in six normal and six insulin-dependent diabetic subjects.

Somatostatin abolished glucagon responses to arginine in both groups, with plasma glucagon declining transiently below basal levels; this occurred despite the fact that the diabetic subjects had fasting hyperglucagonemia and exaggerated glucagon responses during control arginine infusions. In both groups plasma glucose rises seen after arginine were diminished during somatostatin infusions, and, in the normal subjects, insulin responses were also inhibited.

These results demonstrate that somatostatin is a potent inhibitor of glucagon secretion in man. Accordingly, it may prove useful as an adjunct to insulin therapy in treatment of insulin-requiring diabetes mellitus.
Hypoglycemia in Compensated Chronic Renal Insufficiency: Substrate Limitation of Gluconeogenesis
Authors: Garber Alan J , Bier Dennis M , Cryer Philip E , Pagliara Anthony S
Published: December 2014

A woman with diabetes mellitus, compensated chronic renal insufficiency, and multiple episodes of fasting hypoglycemia was studied. On fasting, despite appropriate insulin, glucagon and normal lactate levels, this patient developed early, profound hypoalaninemia followed by hypoglycemia. Glucose and alanine turnover rates were estimated after an overnight fast by the primed injection—continuous infusion of isotopically labeled alanine and glucose. Glucose production (mean ± S.E.) was 36.4 ± 2.8mg./kg. hr. (normal 129.0 ± 10.1 mg./kg. hr., n = 6). Glucose production from alanine was 3.1 ± 0.7 mg./kg. hr. (normal 18.0 ±1.0 mg./kg. hr.). Alanine turnover was 241 ± 11/μmoles/kg. hr. (normal 488 ± 48 μmoles/kg. hr.). These data suggest that an inadequate delivery of an important gluconeogenic substrate—alanine—can exert a significant rate limitation on glucose production thereby resulting in hypoglycemia during fasting.
Serum Enzyme Changes in Diabetic Ketoacidosis
Authors: Knight Anthony H , Williams David N , Spooner Richard J , Goldberg David M
Published: December 2014

A study of thirty-six unselected episodes of diabetic ketoacidosis showed that multiple serum enzyme abnormalities, severe in degree, occurred in eleven (30.6 per cent). Seven could be explained wholly or partly by concurrent illness, such as myocardial infarction or gallstones, but no cause could be found in the other four cases. Since multiple enzyme abnormalities of lesser degree occurred without clinical explanation in a further three cases, the over-all incidence of multiple unexplained enzyme elevation was 19.4 per cent. A single serum enzyme activity was elevated over several consecutive samples during nine episodes: CPK was the enzyme concerned in three, and six were associated with abnormalities in enzymes specific for hepatobiliary disorders.

The prognosis is seriously affected by concurrent illness, but is not altered by the existence of enzyme abnormalities per se, no matter how severe; these may reflect transient leakage of enzymes from hepatocytes reversibly damaged by lysosomal constituents.
Basal Lamina Layering in Diabetes Mellitus: Evidence for Accelerated Rate of Cell Death and Cell Regeneration
Authors: Vracko Rudolf
Published: December 2014

Excessive deposition of basal lamina in capillaries and othei structures of individuals with diabetes mellitus is characterized by formation of multiple layers of basal lamina and accumulation of cell debris between the layers. In capillaries with multiple BL layers, between pericytes and endothelial cells, only a single layer is generally present These and other features suggest that basal lamina formation is a quantified event and that excessive accumulation could be the result of (1) cell death and cell replacement, (2) discrete turning on and off of basal lamina production or (3) defective resorption of old basal lamina layers. Evidence indicating that the major component in the pathogenesis of basal lamina accumulation is cell death and cell regeneration is presented. Whether interrupted production or impaired resorption also contribute to this process is unknown.

The common presence of BL layering in patients with diabetes mellitus indicates that diabetics' cells are different from nondiabetics', the difference manifesting itself by increased rate of cell death. The focal nature of this process suggests further that injurious events in the cells' environment contribute to the pathogenesis of this lesion.

Whatever the cause, the BL characteristics discussed, like rings on cross-sections of tree trunks, give some indication of the number of cell generations which have occurred at that particular site.
Quantitative Study on the Potentiating Effect of Arginine on Glucose-induced Insulin Response in Healthy, Prediabetic, and Diabetic Subjects
Authors: Efendić Suad , Cerasi Erol , Luft Rolf
Published: December 2014

Glucose dose-relations of the early and late insulin responses were established in control, prediabetic and mildly diabetic subjects by performing glucose infusions with varying doses in each subject. Our earlier demonstration that the dose-response curves for both the early and late insulin responses are shifted toward the high glucose region in prediabetes and diabetes was confirmed. In a second series of experiments, a thirty minute arginine infusion was given fifty minutes before the start of the glucose infusion. The insulin response to arginine was reduced in the prediabetics and diabetics. Plasma insulin returned to base line at the start of the glucose infusion in the controls and prediabetics, but not in the diabetics. The early insulin response to glucose infusion was markedly enhanced by pretreatment with arginine at all glucose doses used, both in the controls and the prediabetics, whereas the late response was not modified. The results in the patients with mild diabetes were not conclusive. In the controls and prediabetics, the glucose-insulin dose-response curves for the early response were steeper after pretreatment with arginine. The percentile increase in insulin response was fairly constant throughout the range of hypergly-cemia induced. The insulinogenic index was increased by arginine with a factor of around 2 in controls as well as prediabetics, regardless of the dose of glucose administered.

These results, together with data reported previously by our group, indicate that arginine acts on insulin secretion by magnifying, at a constant rate, the insulinogenic signal of glucose. In prediabetics (and probably also in persons with slight diabetes), in whom the insulinogenic signal of glucose on the β-cell is diminished, arginine exerts quantitatively a similar degree of amplification. Therefore, it seems reasonable to assume that the mechanisms which mediate the amplifying effect of arginine in the β-cell are not deranged in prediabetes.
Recovery from Experimental Diabetes Mellitus in Mice after Pancreas Transplantation
Authors: Kramp R C , Congdon C C , Smith L H
Published: December 2014

Mice made diabetic with alloxan or streptozotocin received subcutaneous transplants of pancreases, which had been ligated six to eight weeks earlier, from three or four isogeneic donors. The course of diabetes in grafted mice was followed by determinations of glucose levels in blood and urine and changes in body weight. Five weeks after transplantation, blood glucose levels were substantially lower in grafted than in nongrafted mice. Recovery from hyperglycemia, defined as a drop in blood glucose below 150 mg./100 mL, was observed only in grafted mice and was greater in streptozotocin- than in alloxan-treated hosts, Normoglycemia was evident in over two thirds of the streptozotocin-treated animals from five weeks after transplantation to the termination of the study (fourteen weeks). The incidence of recovery in alloxan-treated grafted animals was variable, but nevertheless recovery could be demonstrated in comparison to nongrafted controls. Grafted animals returning to normoglycemia showed simultaneously a net gain in body weight and no glycosuria.
Prevalence of Post-glucose-Load Glycosuria and Hypoglycemia in a Group of Healthy Young Men
Authors: Fariss Bruce L
Published: December 2014

Plasma glucose determinations were performed on 4,928 men, and 4,720 urine samples were surveyed for sugar by Tes-Tape two hours after the ingestion of 100 gm. of glucose. Glycosuria of 1 to 4+ was found in 19.3 per cent of the urine specimens. A plasma glucose of 59 mg./100 ml. or less was found in 24.4 per cent of the group.