bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hormonal Control of Intermediary Metabolism in Obese Hyperglycemic Mice: I. The Sensitivity and Response to Insulin in Adipose Tissue and Muscle in Vitro
Authors: Abraham R R , Beloff-Chain Anne 
Published: December 2014

The sensitivity and response to insulin in vitro of (a) the incorporation of U-C-14-glucose into glycogen in the isolated diaphragm muscle, and (b) the oxidation of l-C-14 glucose in the epididymal fat pad and in adipocytes, has been studied in obese hyperglycemic mice fed ad libitum, in obese mice fasted for twenty-four hours and in obese mice maintained on a restricted diet from weaning and in lean mice, at two to four months of age and at six to eight months of age.
In both age groups, there was a significant, although reduced, insulin effect in the muscle from obese mice but this was normal in the six to eight-month-old group of obese mice on a restricted diet.
The glucose oxidation in the epididymal fat pad of the obese mice fed ad libitum was very reduced in both age groups. Fasting the obese mice for twenty-four hours did not restore glucose oxidation to normal, but it was normal in fat pads from obese mice kept on a restricted diet. There was no insulin effect on the fat pad of obese mice in either age group even after a twenty-four-hour fast. The response and sensitivity of the tissue to insulin was partially restored in the obese mice on a restricted diet.
There were only small differences in sensitivity between adipocytes prepared from obese and lean epididymal fat pads. The maximum response to insulin in adipocytes from obese mice was usually lower than that in adipocytes from lean mice at glucose concentrations of 0.03 per cent but equal or higher at glucose concentrations of 0.2 per cent.
The clear responses to low concentrations of insulin of the isolated diaphragm muscle and adipocyte suspension from obese mice on a restricted diet and of the adipocytes from obese mice fed ad libitum, suggest that a decreased sensitivity to insulin at the cellular level is not the primary defect in the obese hyperglycemic syndrome.
Hormonal Control of Intermediary Metabolism in Obese Hyperglycemic Mice: II. Levels of Plasma Free Fatty Acid and Immunoreactive Insulin and Liver Glycogen
Authors: Abraham R R , Dade Erica , Elliott Jennifer , Hems D A 
Published: December 2014

In mice with genetic obesity, the plasma concentration of total free fatty acid (FFA) was not significantly raised, and no abnormality was detected in the response of the plasma level of FFA to noradrenaline. The plasma concentration of immunoreactive insulin (IRI) in the fed state was higher in obese than lean mice, even if glucose was given to lean mice. The content of liver glycogen was consistently higher in obese mice.
Following deprivation of food, plasma concentration of IRI decreased in obese mice, and that of FFA rose at the same rate as in lean mice. In obese mice which had been fasted for twenty-four hours or fed on a restricted quantity of food, the plasma level of IRI remained higher than in lean mice.
On oral administration of glucose to fasted mice, the decline in plasma FFA concentration, compared to that in animals which received saline, was similar in obese and lean mice. In response to glucose, the plasma IRI concentration increased rapidly in obese mice.
These results suggest that there is no primary impairment of adipose tissue triglyceride breakdown (“lipolysis”) in genetically obese mice, and that the hypersecretion of insulin in response to ingestion of food may more closely reflect their primary disorder.
A Survey of Diabetes Mellitus in a Rural Population of India
Authors: Jaya Rao Kamala S , Mukherjee N R , Visweswara Rao K 
Published: December 2014

A survey was carried out among an adult rural population of India to assess the prevalence of diabetes mellitus in undernourished population groups. The subjects subsisted on cereal-based diets inadequate in calories and most were underweight. The prevalence of diabetes, as assessed by the presence of glycosuria, was 2.4 per cent. No age differences were observed among men, whereas the prevalence was higher among women above fifty years of age.
Of the women between twenty to fifty years of age, 49.3 per cent were lactating at the time of the survey. Out of these, 66.5 per cent had lactosuria, the maximum prevalence being observed in the first two years of lactation.
Metabolic Characteristics of Isolated Pancreatic Islets in Tissue Culture
Authors: Andersson Arne , Hellerström Claes 
Published: December 2014

The present studies were performed to investigate the possibility of culturing isolated pancreatic islets in vitro in a system which should allow assessment of both morphologic and metabolic alterations in the islet cells after prolonged periods of incubation. For this purpose, isolated islets from adult mice were maintained in stationary organ cultures in a nutrient medium containing glucose at a concentration of either 1.2 mg./ml. or 5 mg./ml. After six or twelve days in culture, the islets were studied with regard to light-microscopic appearance, rates of oxygen consumption, glucose oxidation, insulin release and insulin content. The metabolic rates were determined in short-term incubations (30–150 minutes) so that relevant comparisons with freshly isolated mouse islets could be performed.
As evidenced by light microscopy, there was an excellent morphologic preservation of islets cultured in either the high or the low glucose medium. Similarly, the rates of oxygen consumption, glucose oxidation and insulin release responded responded to glucose throughout the culture period in a manner qualitatively similar to these responses in freshly isolated islets. The most obvious quantitative metabolic alterations observed in the cultured islets were increased rates of respiration and glucose oxidation and a decreased basal rate of insulin release. Islets cultured in the high glucose medium responded to glucose with a higher glucose oxidation and a lower rate of insulin release than those cultured in the low glucose medium for a similar period of time. The insulin content of the islets decreased markedly during the initial six days of the culture period.
The results indicate that with the present technic for organ culture of isolated mouse islets, the β cells retain several of their characteristic metabolic responses during prolonged in vitro culture. The method should be useful for providing new information on the long-term effects in vitro of various factors on the structure and metabolism of the pancreatic β cell.
Proinsulin and C-Peptide in Blood
Authors: Rubenstein Arthur H , Block Marshall B , Starr Jerome , Melani Franco , Steiner Donald F 
Published: December 2014

Proinsulin-like components (proinsulin and its intermediate forms, PLC) and C-peptide have been identified as secretory products of the pancreatic beta cells in addition to insulin. Because a specific human proinsulin antiserum is not yet available, serum PLC can be measured with an insulin or C-peptide antiserum and a human proinsulin standard after separation of insulin and C-peptide by gel filtration. Assay of unextracted serum with these two immunoassay systems measures total insulin immunoreactivity (insulin + PLC) and C-peptide immunoreactivity (C-peptide + PLC), respectively.
Fasting PLC in normal subjects ranged between 0.05 and 0.4 ng./ml. After oral glucose, PLC levels rose more slowly than insulin and peaked at a later time. In relation to insulin, the percentage PLC was high in the basal state and two to four hours after glucose. The serum PLC concentration has also been measured in a variety of disease states including obesity, acromegaly, myotonic dystrophy, uremia, myxedema and Cushing's syndrome. However, the most frequent and marked abnormality in its level has been found in patients with islet cell tumors.
Equimolar amounts of C-peptide and insulin were found in serum of subjects with a wide range of insulin values. Thus the C-peptide level can be used as an indicator of beta cell secretory function. This application is especially useful in diabetic patients who develop circulating insulin antibodies in response to exogenous bovine or porcine insulin therapy. Measurement of serum C-peptide and proinsulin in these subjects has shown varying degrees of beta cell failure as well as marked fluctuations in secretory capacity in individual patients with progression of their disease.
Preliminary results have indicated the immunological heterogeneity of other circulating peptide hormones and have shown that they may be synthesized and stored in a form different from the secreted molecule. The discovery of proinsulin has thus opened up new and exciting areas which may have wide application in endocrinology.
Increase in Plasma Immunoreactive Insulin Following Administration of Insulin to the Gastrointestinal Tract of Rabbits
Authors: Shichiri Motoaki , Okada Akira , Karasaki Kenkichi , Kawamori Ryuzo , Shigeta Yukio , Abe Hiroshi 
Published: December 2014

Changes in plasma insulin levels in response to enterai administration of insulin have been studied in rabbits.
Insulin, when administered to the stomach, did not cause hypoglycemia at doses up to 150 U./kg. When insulin at doses over 40 U./kg. was infused to the upper jejunum via an indwelling catheter, there was a slight but significant increase in plasma insulin levels, followed by a significant fall in blood glucose. A considerable increase in plasma insulin was observed when insulin at doses over 20 U./kg. was infused to the Thiry-Velia loop of the jejunum in which no pancreatic secretion entered. With a dose of 100 U./kg., the mean plasma insulin rose promptly to the peak of 241 μU./ml., followed by a severe hypoglycemia.
As judged by hypoglycemie and immunological responses, insulin can be absorbed from the intestine in a physiologically active form, but the fraction absorbed is relatively small.
Characteristics of Nonsuppressible Insulin-like Activity in Fasting Human Serum
Authors: Meade Robert C , Klitgaard Howard M , Holanders Egils 
Published: December 2014

Insulin-like activity (ILA) and nonsuppressible insulinlike activity (NSILA) of fasting normal human serum have been studied following fractionation by cation resin chromatography, or extraction with acid-ethanol or ethanol. Studies of solubility, heat stability and immunosuppressibility suggest three different fractions, none of which is immunoassayable insulin. The total activity of the fractions was usually several times that of the original serum.
“Bound” NSILA, which binds to a cation resin column, appears to be a smaller molecule than “free insulin” NSILA found in the column effluent. Our studies suggest that the column effluent NSILA is converted to the smaller “bound” NSILA by acid-ethanol extraction. Although the column effluent NSILA is partially suppressible with guinea pig antiserum, only a trace amount of immunoassayable insulin was found in this fraction.
Spontaneous Diabetes Mellitus in Mystromys Albicaudatus: Repeated Glucose Values from 620 Animals
Authors: Stuhlman Robert A , Packer James T , Doyle Richard E 
Published: December 2014

The serum glucose values of 1,423 blood samples from 620 Mystromys albicaudatus have been determined and defined as ortho glycemie or hyperglycemie. Analyses of variance tests and regression analyses of the data revealed a significant difference between orthoglycemic and hyperglycemie serum glucose means and indicated that serum glucose is not affected by sex, inbreeding, or age in these animals. However, within classifications of orthoglycemic and hyperglycemie, weight did affect serum glucose. Therefore, while obesity did not occur during this study, obese-hyperglycemia syndromes might be expected should the animals become overweight.
The data and their analyses are strongly indicative that spontaneous diabetes mellitus in M. albicaudatus, as related to hyperglycemie, is very similar to the disease in man.
Neutralization of the Biologic Activity of Human Serum Bound Insulin by Potent Insulin Antisera
Authors: Antoniades Harry N , Simon James D 
Published: December 2014

The in vivo biologic activity of human serum bound insulin is significantly neutralized in vivo, in intact mice and rats, by undiluted guinea-pig insulin antisera (GPAIS). Significant neutralization of biologic activity on both muscle and adipose tissue glycogen synthesis was observed with the addition of GPAIS.
The present studies demonstrate that the concentration of insulin antisera is critical for the neutralization of in vivo biologic activity of bound insulin. In addition, the results suggest that bound insulin injected intraperitoneally into mice or rats may be modified in such a way to allow reactivity with insulin antisera, as judged by loss of biologic activity.
Drug-induced Hypoglycemia: A Review Based on 473 Cases
Authors: Seltzer Holbrooke S 
Published: December 2014

Both recognition and prevention of drug-induced hypoglycemia require awareness of the clinical conditions favoring its occurrence and the drugs and drug combinations most likely to cause it. Restricted food intake, age, hepatic disease and renal disease are the main predisposing factors, individually and even more so in combination.
Everyone in general, and insulin-requiring diabetics in particular, should always eat carbohydrate whenever they drink alcohol.
Sulfonylurea hypoglycemia has been reported often in diabetics older than fifty years, with more cases treated with chlorpropamide being reported than cases treated with other sulfonylureas ; it should therefore be used warily in older patients, and only when they are under daily observation by family or friends. In elderly diabetics taking any sulfonylurea agent, warfarin should be used for anticoagulation instead of bishydroxycoumarin, indomethacin for arthritic pain instead of phenylbutazone, and another agent than sulfisoxazole for urinary tract infections. Also in elderly diabetics using sulfonylureas, therapeutic doses of salicylates, monoamine-oxidase inhibitors and probably pro-pranolol should be co-administered with caution, including frequent blood glucose monitoring as long as necessary. Finally, the danger of refractory hypoglycemia in the newborn .proscribes the mother's use of sulfonylureas during the last month of pregnancy.
Drug-induced hypoglycemia is now so relatively common that virtually every unconscious patient should be considered hypoglycemie until immediate estimation of the blood sugar level rules the condition in or out. If it is ruled in, the clinician should promptly start 10 per cent glucose by vein and plan to maintain it uninterruptedly for one or more days, with added hydrocortisone and glucagon if necessary, until persistent hyperglycemia guarantees that all drug effects have worn off.
Increased Production of Fructose by the Brain in Dogs Made Diabetic by Alloxan and by Growth Hormone
Authors: Spinowitz Bruce S , Altszuler Norman 
Published: December 2014

The cerebrospinal fluid (CSF) concentration of fructose is elevated in diabetes. In the alloxan-diabetic animal this elevation has been attributed to increased fructose production by the brain. The present study seeks to determine if the increased fructose production is due to hyperglycemia or insulin deficiency. C-14-fructose was injected into the CSF in anesthetized dogs, and from its rate of removal the turnover of CSF fructose was calculated. Since plasma fructose does not pass readily into CSF, the fructose flux reflects fructose production by brain.
In dogs made diabetic with growth hormone, which results in hyperglycemia and hyperinsulinism, CSF fructose levels and turnover rate are significantly elevated. Restoration of normoglycemia by a thirty-six hour fast returns CSF fructose levels to normal. Glucose infusion to elevate plasma glucose for four hours in normal dogs raises plasma fructose but not CSF fructose levels. Similarly, eliminating hyperglycemia for three hours in alloxan-diabetic dogs by insulin infusion decreases plasma fructose, but CSF fructose levels remain elevated. Daily insulin injections do restore CSF fructose to normal.
It appears that increased fructose production by the brain in diabetes depends on hyperglycemia and the underlying metabolic processes for this require a number of hours to develop or be expressed.
Psychological Effects of a Special Summer Camp on Juvenile Diabetics
Authors: McCraw Ronald K , Travis Luther B 
Published: December 2014

A group of children with diabetes mellitus were evaluated for self-esteem and manifest anxiety before and after attending a special summer camp. Both males and females showed significant increases in their self-esteem and decreases in manifest anxiety. In both areas, the girls showed a greater improvement than the boys but this was thought to be due partially to the lower initial self-esteem in the females.
A comparison was made between these children and a matched group of diabetic children who didnot attend camp. In this group, there was also an improvement in both variables on retesting. Theimprovements for the camp group were always greater than for the controls, but only in the case of female self-esteem was the difference statistically significant.
Effect of Acetyl Choline on the Secretion of Glucagon and Insulin from the Isolated, Perfused Canine Pancreas
Authors: Iversen Johan 
Published: December 2014

During perfusions with glucose concentrations of 25 and 150 mg./100 ml., the effect of infusions of acetyl choline on glucagon and insulin release was investigated in five perfusion experiments. Acetyl choline at concentrations of 10 to 100 μM. stimulated release of glucagon both at the low glucose strength as well as at the high concentration, which in itself inhibits basal glucagon release. Glucagon was released in a monophasic pattern, resembling the release pattern found after catecholamines and contrasting with the biphasic pattern obtained after stimulation with gastrointestinal hormones and amino acids, as previously reported from our laboratory.
Acetyl choline always stimulated release of insulin in a biphasic pattern, at the high glucose concentration, while no consistent effect was obtained at the low glucose concentration. At the termination of the acetyl choline infusions, a rebound increase in insulin was observed during perfusion with both low and high glucose concentrations.
Infusion of atropine at a concentration of 25 μM. completely abolished the stimulatory effect of acetyl choline on both glucagon and insulin release.
The results suggest that the parasympathetic nervous system may play a direct role in the control mechanism of the release of the pancreatic hormones during food ingestion.
Lipolytic Effects of High Concentrations of Insulin on Isolated Fat Cells: Enhancement of the Response to Lipolytic Hormones
Authors: Lavis Victor R , Williams Robert H 
Published: December 2014

When isolated rat fat cells were incubated with epinephrine or adrenocorticotropin, release of glycerol and nonesterified fatty acids was greater in the presence of 40 ng. per milliliter of insulin than with 2 ng. per milliliter of insulin. Enhanced lipolysis with the higher dose of insulin occurred in the absence of added carbohydrate, did not involve re-esterification of fatty acids, could not be attributed to the presence of glucagon, and was abolished by incubation with anti-insulin gamma globulin or by prior trypsinization of fat cells. Insulin did not augment lipolysis induced by theophylline or added cyclic 3′,5′-adenosine monophosphate (cyclic AMP).
In the presence of 5.5 μM. epinephrine, the initial rate of lipolysis was decreased by insulin in the amount of 2 ng. per milliliter but not by the higher dose, 40 ng. per milliliter. The ability of fat cells to continue accelerated lipolysis was prolonged by 40 ng. per milliliter of insulin, compared with epinephrine alone.
Cycloheximide, and probably puromycin, partially inhibited enhancement of lipolysis by insulin, 40 ng. per milliliter, in the presence of 5.5 μM. epinephrine. This effect of cycloheximide first appeared 120 minutes after exposure of cells to the drug. Responses to epinephrine alone and to 2 ng. per milliliter of insulin were not affected by these drugs.
These results imply that insulin can enhance the lipolytic activity of hormonal stimulators of adenylate cyclase by actions which at least in part require protein synthesis. Indirect evidence suggests that cyclic AMP mediates the lipolytic effects of insulin.
Factors in the Pathogenesis of Experimental Nonketotic and Ketoacidotic Diabetic Stupor
Authors: Joffe B I , Seftel H C , Goldberg R , As M Van , Krut L , Bersohn I 
Published: December 2014

In an attempt to elucidate some of the factors responsible for the absence of significant ketosis in hyperosmolar nonketotic diabetic stupor, an experimental model was created in rats. This involved the intravenous administration of alloxan (40 mg. per kilogram) to produce moderate hyperglycemia, followed by daily hydrocortisone injections and dextrose feeding. For comparison, ketoacidotic diabetic rats and various control situations were also studied.
The biochemical profiles of the nonketotic and ketoacidotic diabetic rats resembled those of their clinical counterparts, although some discrepancies were apparent. Attention was. directed at measuring plasma free fatty acid (FFA) and ketone body levels, as well as hepatic glycogen and portal and peripheral plasma immunoreactive insulin (IRI) concentrations in the diabetic and control groups. The hyperosmolar nonketotic diabetic rats were characterized by: a mean plasma FFA level intermediate between that of the controls and that of the ketotics; modest rises in 3-hydroxybutyrate and acetoacetate; and a striking elevation in hepatic glycogen concentration. In addition, their mean portal IRI value resembled that of the control animals (both significantly greater than ketotics) but their mean peripheral plasma IRI value was similar to that of the ketotics (both significantly lower than controls).
It is suggested that the absence of severe ketosis in the hyperosmolar nonketotic diabetic rats was, at least in part, due to the ability of their glycogen-rich, ‘insulinized’ livers to metabolize incoming FFA largely along nonketogenic pathways. The relevance of these findings to the clinical situation is briefly considered.
Renin, Angiotensin, and Norepinephrine in Alloxan Diabetes
Authors: Christlieb A R 
Published: December 2014

The renin-angiotensin system and catecholamines were evaluated in short term alloxan diabetic rats which were either “severely diabetic” (polyuric with serum glucose &gt; 450 mg. per 100 ml.) or “mildly diabetic” (normouric with serum glucose &lt;450 mg. per 100 ml.). Plasma renin activity (PRA), renal renin activity (RRA), and the amount of angiotensin II producing an acute 10 mm Hg increase in blood pressure were all significantly decreased in the diabetic rats with this decrease correlating inversely with the severity of the diabetes. Insulin treatment of these rats resulted in partial normalization of angiotensin II responsiveness, PRA, and blood urea nitrogen. Injection of alloxan directly into the left renal artery did not decrease RRA. Protection of the left kidney during systemic alloxan injection did not prevent the decrease in renal renin activity. Streptozotocin-treated diabetic rats had increased vascular responsiveness to injected angiotensin II. Norepinephrine sensitivity (amount producing a 10 mm Hg increase in blood pressure) and norepinephrine stores (blood pressure response to tyramine) were normal in both alloxan- and streptozotocin-treated rats.
Blood volume as related to lean body mass was elevated in the severely diabetic rats thus suggesting one possible mechanism for the decrease in the renin-angiotensin system.
These results suggest that (1) norepinephrine responsiveness and norepinephrine stores are normal, and (2) there is suppression of RRA leading to decreased PRA and increased vascular reactivity to angiotensin II in the acutely diabetic alloxan-treated rat. Further, these abnormalities appear to be related to the degree of diabetes as assessed by serum glucose and twenty-four hour urine volume.