bluuebunny/crossref_metadata_2025 huggingface dataset:
Diabetes Incidence: A Two-year Follow-up of 10,000 Men in a Survey of Ischemic Heart Disease in Israel
Authors: Herman Joseph B , Medalie Jack H , Kahn Harold A , Neufeld Henry N , Riss Egon , Perlstein Tamar
Published: December 2014

In 1963, 10,059 men aged forty years and over were examined in an I.H.D. survey and 9,711 of them were re-examined two years later. At both these examinations suspect diabetics werescreened out by a casual blood glucose value and/or a positive history of diabetes. Further information was collected on all these suspect diabetics to enable their classification into diabetic categories using similar criteria on both occasions.

Among 9,079 persons judged at risk of developing diabetes, 144 new cases of diabetes were discovered two years after the 1963 examination. The over-all two-year incidence rate for men over forty was 15.5 per thousand. Four regions of origin, Central Europe, Southeastern Europe, Israel and North Africa had incidence rates approximately equal to the over-all rate. The age adjusted incidence rate for men from Eastern Europe was lower (8.5 per 1,000) and from the Middle East higher (20.3 per 1,000) than the average.
Diabetogenic Effects of Streptozotocin in Rhesus Monkeys
Authors: Pitkin Roy M , Reynolds W Ann
Published: December 2014

Streptozotocin was administered to twelve rhesus monkeys in single intravenous doses of 30, 45, or 60 mg. per kg. Post-treatment study of plasma glucose and immunoreactive insulin levels and pancreatic histology confirmed previous observations in lower animals that streptozotocin produces a diabetic-like state due to its cytotoxic action on pancreatic beta cells. In contrast to its reported effect in rodents, however, streptozotocin in monkeys was somewhat more variable in its diabetogenic action and appeared to have a narrower margin of safety between diabeto genesis and toxicity. Of seven animals given 45 mg. per kg., five developed hyperglycemia and relative hypoinsulinemia and a sixth had impaired glucose tolerance. Two monkeys, both receiving 60 mg. per kg., became frankly diabetic while all three receiving 30 mg. per kg. showed no alteration in glucose tolerance.
Hyperzincuria of Diabetes Mellitus and Possible Genetical Implications of This Observation
Authors: Pidduck Heather G , Wren Peter J J , Price Evans David A
Published: December 2014

A study of the urinary zinc excretion pattern of diabetic subjects, relatives of diabetics and controls has been undertaken. Diabetics show a significant hyperzincuria as compared with controls. Family studies have indicated that urinary zinc excretion could be under polygenic control. The genes involved could be important in the diabetic and prediabetic diathesis.
Personality Patterns in Patients with Diabetes Mellitus of Long Duration
Authors: Murawski Benjamin J , Chazan Bernard I , Balodimos Marios C , Ryan Jerome R
Published: December 2014

One hundred and twelve patients with diabetes for twenty-five to forty-eight years were studied with the Minnesota Multiphasic Personality Inventory. Of these, sixty-seven had been awarded the Quarter Century Victory Medal, having been found free of vascular complications after twenty-five or more years of diabetes. The personality inventory disclosed statistically significant differences between medal and nonmedal patients in three of the thirteen scales, and three other scales approached significance. When divided as to sex, different personality patterns characterized the groups but in both sexes nonmedal patients had significantly higher hypochondriasis scores. When depression, a frequently elevated score, was excluded, significantly more nonmedal patients had other abnormal scale scores (above 2 standard deviations). The differences in scores between medal and nonmedal patients warrant early personality screening and appropriate therapy to help the adaptation process of the person with diabetes.
Production of Nonimmunoassayable Insulin-like Material by Perfused Rat Liver
Authors: Gershoff S N , Weich N L , Antoniades H N
Published: December 2014

The perfusion of isolated rat liver with media containing 74 μU. bovine crystalline insulin per ml. resulted in a rapid loss of immunoassayable insulin accompanied by the appearance of nonimmunoassayable insulin-like activity as measured in vivo by a rat intraperitoneal assay for insulin activity. The material with insulin-like activity could be absorbed and separated from insulin on Dowex-50W × 8 resin (Na+ cycle). Fractionation on Sephadex Q-100 indicated that it has a molecular weight above 40,000 with possible peaks of activity between 40,000 to 60,000 and above 90,000. Small amounts of nonimmunoassayable insulinlike activity were released by perfused livers even when insulin was not added to the perfusion media. When insulin was added to the media, there was a marked increase in the release of nonimmunoassayable insulin-like activity.
Regulation of Insulin Release by Pancreatic Glucagon
Authors: Colwell A R , Zuckerman Leon
Published: December 2014

In order to localize the site of its insulinogenic stimulus, glucagon was infused individually into the pancreas, liver, and peripheral circulation of normal dogs. Blood levels of insulin, glucose and nonesterified fatty acids were monitored in the femoral artery, portal and hepatic veins. The pancreatic artery infusions provoked a more rapid and marked insulin release initially than the same amount of glucagon given into the portal or femoral vein. The degree of hyperglycemia was comparable in the three groups, although the pancreatic group had more suppression of fatty acids probably related to the enhanced insulin secretion.

Intrapancreatic infusion of glucagon in amounts sufficient to release insulin always produced concomitant hyperglycemia. In comparison, small amounts of glucose administered by the same route released insulin without elevating the blood glucose level. Larger quantities of glucose, calculated to produce insulin levels similar to those attained with glucagon, provoked hyperglycemia of lesser magnitude and shorter in duration.

The effect of epinephrine on glucagon-stimulated insulin infusion. A quantity of intrapancreatic epinephrine which normally inhibits the glucose stimulus had no effect on delaying the insulin response until the amount of epinephrine was tripled.

Simultaneous measurements of insulin and glucose in the hepatic venous blood during the intrapancreatic infusion resulted in response curves similar to those found in the portal vein. Even though the hepatic venous glucose values were almost identical during the infusions at the three different sites, insulin values were two to three times lower with portal or femoral than with pancreatic infusions.

We conclude from the data that glucagon does play an independent role in the release of insulin from the pancreas, but that its effectiveness is less than glucose under normal circumstances. The glucagon stimulus is effective despite the presence of ordinary amounts of epinephrine. Since the magnitude of the insulin released from intra-portal glucagon is limited and delayed, the importance of its action as a gut factor in response to an oral glucose load is challenged.
On a Mathematical Model for the Analysis of the Glucose Tolerance Curve
Authors: Corte M Della , Romano S , Voeghelin M R , Serio M
Published: December 2014

Three hundred and seventeen oral glucose tolerance curves have been analyzed by a mathematical model (Ackerman's model).

By application of the model to continuous venous infusion the validity of the Ackerman's hypothesis on the glucose intestinal absorption has been confirmed. The results demonstrated that the intestinal absorption rate of glucose was not statistically changed in diabetes mellitus, but decreased with age.

The period of curve T, which characterizes the glucose-insulin feed-back, the glucose fasting level and the coefficient α, which characterizes insulin removal rate independent of blood glucose and the decrease of blood glucose independent of insulin, resulted in significant differences between normal and diabetic subjects. The error involved in this method was about 7.5 per cent.
Glucose Tolerance During the Menstrual Cycle
Authors: Macdonald I , Crossley J N
Published: December 2014

Oral glucose tolerance tests were carried out at weekly intervals in thirteen young women and six young men. There was a greater variation in response by the young women compared to the young men. This greater variation was due to altered responses during different phases of the menstrual cycle. It is suggested that the fluctuations in the oral glucose tolerance test during the menstrual cycle may be secondary to alterations in gastric activity.
Excessive Serum Insulin Response to Oral Glucose in Obesity and Mild Diabetes Study of 501 Patients
Authors: Chiles Ross , Tzagournis Manuel , Catalano E J
Published: December 2014

Glucose tolerance tests and immunoreactive insulin responses were analyzed in 203 subjects with abnormal glucose tolerance and in 298 nondiabetics. All subjects were grouped as obese (greater than 115 per cent of ideal body, weight) or lean. Those with an abnormal glucose tolerance test were further subdivided: (1) Normal fasting glucose and one or more abnormal subsequent values, and (2) elevated fasting glucose and an abnormal tolerance test. The total mean glucose and insulin concentrations, expressed as the areas under the three-hour glucose tolerance curves, were compared in the six subgroups. Hyperinsulinism was found in obese nondiabetics as compared to lean nondiabetics. Mildly impaired glucose tolerance in both obese and non-obese patients was associated with increased insulin levels compared to nondiabetics. Despite increased immunoreactive insulin levels in subjects with impaired glucose tolerance, the concentrations were less than expected for corresponding glucose levels during the early portion of the tolerance test. Decompensated diabetes, manifested by fasting hyperglycemia, was associated with absolute as well as relative deficiency of endogenous insulin. While definite trends in glucose-induced insulin responses could be determined in specific groups, there was marked individual variation.
Tris (Hydroxymethyl) Aminomethane (THAM) Induced Stimulation of Insulin Release by Islets of Langerhans Previously Isolated from Rat Pancreas
Authors: Fedynskyj Nathalie M , Beck Lyle V
Published: December 2014

Islets isolated from rat pancreas were studied in regard to release of immunoreactive insulin (IRI) as influenced by changes in glucose concentration and pH and type of buffer in the incubation media. The pH of the media was varied from 7.4 to 9.0. For phosphate and bicarbonate buffered media, change in pH did not result in significant change in IRI release rates. For media containing the pH buffer and chelating compound THAM (Tris [hydroxymethyl] aminomethane), IRI release increased significantly with increase in either THAM concentration or pH. Since increase in pH results in increase in that fraction of THAM which is in the unionized, therefore presumably more readily penetrating form, it is postulated that THAM molecules penetrate and act at intracellular loci to induce insulin release, possibly by chelating Zn complexed with insulin in beta cell granules.
Effect of Insulin on FFA Mobilization and Ketosis in Fasting Pregnant Rats
Authors: Chernick Sidney , Novak Milan
Published: December 2014

The concentrations of FFA and ketone bodies in plasma increased more in rats pregnant for eighteen days than in nonpregnant rats when both groups were fasted for two days. The immunoreactive insulin content of plasma was the same in fasted nonpregnant and pregnant rats whether the latter were ketotic or not. Hence, decreased circulating insulin, per se, did not appear to be the primary cause of ketosis in fasting pregnant rats. FFA mobilization was not suppressed completely by insulin in ketotic pregnant rats.

The adipose tissue of pregnant rats showed impaired metabolism of glucose and increased FFA release in vitro. Lipolysis, in the presence or absence of insulin, was greater in adipose tissue of pregnant than in that of nonpregnant rats. Ketogenesis by liver slices of pregnant rats was greater than that of nonpregnant control rats and was not reduced thirty minutes after insulin injection despite a 50 per cent lowering of the concentration of plasma FFA and ketone bodies during this time.

It is suggested that the ketosis of fasting in pregnant rats is caused by increased lipolysis in their adipose tissues and that increased FFA release is due to the absence of sufficient glucose to support re-esterification in the adipose tissues. The small effect of insulin (0.2 and 1.0 U., subcutaneously) on the plasma FFA may be due to the very low plasma glucose in fasting pregnant rats.
Effect of Streptozotocin-induced Diabetes on Pancreatic Insulin Content of the Fetus
Authors: Golob Erich K , Rishi Surendra , Becker Kenneth L , Moore Charles , Shah Narendra
Published: December 2014

Diabetes was produced in five-day pregnant Sprague- Dawley rats by intravenous injection of 40 mg./kg. body weight of streptozotocin. Normal pregnant rats were used as controls. Pancreases of the mothers and their offsprings were extracted by acid-alcohol and the insulin measured by immunoassay using rat insulin as a standard.

Nonfasting blood sugar of the streptozotocin-treated pregnant rats was 285 ± 18 mg./100 ml. and their pancreatic insulin concentration was 5.9 ± 1 μg./gm. compared to 103 ± 3 mg./100 ml. and 44.2 μg./gm., respectively, in the normal rats.

Fetal pancreases of streptozotocin-induced diabetic pregnant rats and normal animals were obtained on Days 18, 19, and 21 of gestation, and on Day 4 after birth. The pancreatic insulin concentration of fetuses of diabetic mothers rapidly and progressively increased from 8.0 ± 0.9 μg./gm. on Day 18 to a peak of 63.0 ± 9.0 /μg./gm. on Day 21. On Day 4 after birth, the value was 312 ± 109 μg./gm. The total pancreatic insulin content also progressively increased to a prenatal peak of 0.84 ± 0.15 μg. on Day 21. The pancreatic insulin concentration of fetuses of normal mothers was not significantly different from those of diabetic mothers. There was no correlation between the elevation of maternal blood sugar and the insulin concentration of the fetal pancreas. The total pancreatic insulin content of fetuses of diabetic rats was less than those offspring of the normal rats on Day 18 and Day 4 after birth, but was not significantly different on Days 19 and 21. The lower insulin content found in fourday-old rats born of diabetic animals was probably related to their inability to obtain adequate nourishment from their very sick mothers.
Evidence for a Feedback Inhibition of Insulin on Insulin Secretion in the Isolated, Perfused Canine Pancreas
Authors: Iversen Johan , Miles David W
Published: December 2014

An isolated in vitro canine pancreas per fusion preparation is described which is suitable for prolonged (five hours) study of insulin secretion. The preparation remains in good condition throughout the experimental period judged by various parameters.

Feedback inhibition of insulin on insulin secretion was studied in the preparation. Experiments were performed at different concentrations of glucose in the influx medium. At 150 mg. per cent of glucose a considerable reduction of the insulin secretion was obtained when exogenous porcine insulin was added to the influx medium in concentrations from 180 μU./ml. to 420 μU./ml.

In eight experiments where the exogenous insulin concentration in the influx medium was equal to or exceeded pre-inhibition efflux values the obtained insulin inhibition amounted to 25-78 per cent of the pre-inhibition values. In one of the eight experiments the exogenous insulin concentration was less than the pre-inhibition value; however, the same effect was obtained.

A feedback mechanism of insulin on insulin secretion from the beta cell has thus been demonstrated at levels of perfusate insulin which occur in vivo.
Effect of Diabetes on the Biosynthesis of the Renal Glomerular Basement Membrane: Studies on the Glucosyltransferase
Authors: Spiro Robert G , Spiro Mary Jane
Published: December 2014

Kidney glucosyltransferase (UDP-glucose: galactosylhydroxylysine-basement membrane glucosyltransferase), which is involved in the synthesis of the hydroxylsine-linked disaccharide units of glomerular basement membrane, has been measured in the renal cortices of normal and alloxan diabetic rats. The level of this enzyme in diabetic kidneys was found to be significantly elevated over that of age-matched controls, expressed either as specific or total activity, at all times studied (one to five months). However the difference between the normal and diabetic animalsincreased with the duration of the disease. When short-term diabetics were treated with insulin, the level of the glucosyltransferase could be restored to normal. Insulin treatment of long-term diabetic animals, which were more difficult to control, brought the enzyme level close to normal but did not completely restore it.

The glucosyltransferase activity in several other tissues of the alloxan diabetic rat, including lung, liver, testes, spleen, and uterus, did not show any significant elevation over that of the normal.

Measurement in kidney of a glycosyltransferase (UDP-galactose :N-acetylglucosamine-glycoprotein galactosyltransferase) involved in the synthesis of a different type of carbohydrate unit did not show the marked elevation noted for the glucosyltransferase.

It is believed that the insulin-reversible glucosyltransferase elevation of the diabetic renal cortex reflects the increased basement membrane synthesis occurring in this tissue and indicates that this process is directly or indirectly under the control of this hormone.
Evidence that Glucose Load Is an Important Determinant of Plasma Insulin Response in Normal Subjects
Authors: Peterson Daniel T , Reaven Gerald M
Published: December 2014

Two consecutive oral glucose tolerance tests were performed on twelve healthy, malemedical students, in which each subject received 20 and 40 gm. of glucose per square meter body surface area. The tests were conducted one week apart, and the sequence in which the two glucose loads was given was randomized. The larger glucose load elicited anincrease in both plasma glucose and immunoreactive insulin response. However, the increase in the plasma insulin response was much greater than the increase in plasma glucoseresponse. Thus, the insulinogenic index, denned as the plasma insulin level divided bythe plasma glucose level, significantly increased as the glucose load increased. These results indicate that glucose load is an important determinant of plasma insulin response, and that in any individual the plasma insulin response is not a simple linear function of coexisting plasma glucose concentration.
Effects of a New Oral Hypoglycemic Agent on Glucose and Insulin after Oral Glucose Loading: A Controlled Study
Authors: Ryan Jerome R , Maha George E , McMahon F Gilbert , Kyriakopoulos Adrian
Published: December 2014

l-(2-pyrimidinyl)-4-imino-l, 4-dihydropyridine hydrochloride is a new compound which after oral administration of a single dose of 400 mg. causes significant reductions of hyperglycemia and insulin response in human subjects after an oral glucose load. These results were obtained when compared to a single dose of 200 mg. of phenformin hydrochloride or placebo in a double-blind completely randomized crossover study with placebo and phenformin. Both drugs also produced a significant fall in the fasting serum glucose value before the oral glucose load without any significant effect on serum insulin values. Both drugs produced similar adverse symptoms in the six healthy subjects who participated in the study.
Intravascular Sickling Associated with Diabetic Ketoacidosis
Authors: Jurgensen J C , Whitehouse F W , Oxley M J , Saeed S M
Published: December 2014

A Negro patient presented with diabetic ketoacidosis. Following usual therapy and an inchoate clinical response, the patient worsened, became comatose and died. Postmortem examination indicated diffuse intravascular sickling as a significant antemortem mechanism in this patient's death.
Use of Sheep Insulin in Insulin Allergy
Authors: Kreines Kenneth
Published: December 2014

A case of mild diabetic ketoacidosis and severe allergy to beef-pork NPH insulin is described. Intradermal tests using insulin derived from various species led to the successful use of sheep insulin.
Physiology of Insulin In Man: The Banting Memorial Lecture 1971
Authors: Cahill George F
Published: December 2014

Insulin serves as the body's signal for the fed or fasted state. High insulin levels, the “fed” signal, initiate tissue uptake and storage of fuels. Low insulin levels, the “fasted” signal, initiate mobilization of stored fuels from tissue stores, the rate being proportional to the lowness of the insulin. Certain metabolic states such as obesity or trauma alter the concentration of insulin at which no net transfer of fuel occurs, resulting in insulin resistance or hyper-sensitivity.
Cephalic Phase of Insulin Secretion in Obese Adolescents
Authors: Parra-Covarrubias Adalberto , Rivera-Rodriguez Irene , Almaraz-Ugalde Arturo
Published: December 2014

The influence of a visual and olfactory meal stimulus on plasma insulin, free fatty acids and glucose levels, was studied in six obese, nondiabetic young persons.

There was a significant increase in plasma immunoreactive insulin with a simultaneous decrease in plasma free fatty acids without demonstrable changes in plasma glucose. The observed rise in plasma immunoreactive insulin most probably is reflex in nature. However, all levels of the nervous system including cerebral cortex, reticular formation and hypothalamus, may play different roles in the facilitation or inhibition of such reflex. The participation of one or several of the gastrointestinal hormones, such as secretin or gastrin, could explain the delayed rise in plasma insulin. Dietary habits, appetite, palatability of the offered meal and a relaxed and tranquil patient seem to be essential factors to be taken into consideration, if success is to be achieved in this type of experimental study.
Diabetic Retinopathy: New Vessels Arising from the Optic Disc: I. Grading System and Natural History
Authors: Kohner E M , Panisset A , Cheng H , Fraser T R
Published: December 2014

1. A grading method for new vessels arising from the optic disc is described. The grading system has been used to study the natural history of new vessels in forty-four eyes of thirty diabetic patients.

2. While some eyes showed considerable changes, the mean progression of new vessels in the entire group was slight and only reached one grade in four years.

3. The most striking feature of the study was the number of eyes which could not be fully assessed at different times during the follow-up period. Eyes became unassessable because of vitreous hemorrhage or retinitis proliferans. These increased from 18 per cent at six months to 66 per cent at four years. Both of these were more common when higher grading values of new vessels were reached.

4. The visual acuity deteriorated in twenty-five eyes. In nineteen of the eyes the deterioration was three lines or more; fifteen eyes became blind. The commonest cause for visual deterioration was vitreous hemorrhage.
Hepatic Enzyme Activities in Streptozotocin-Diabetic Rats Before and After Insulin Treatment
Authors: Chang Albert Y , Schneider Diana I
Published: December 2014

Streptozotocin causes hyperglycemia and hypoinsulinemia in rats. Striking elevations in hepatic phosphoenolpyruvate carboxykinase, pyruvate carboxylase, hexosediphosphatase and glucose-6-phosphate, and dramatic decreases in glucokinase, pyruvate kinase and 6-phosphogluconate dehydrogenase are observed in these diabetic animals. Daily treatment of insulin in diabetic rats brings about increase in liver weight, glycogen and soluble protein contents, and in the levels of glucokinase, pyruvate kinase, 6-phosphogluconate dehydrogenase and lactate dehydrogenase. In terms of unit/gm. liver, the activities of PEP carboxykinase, glucose-6-phosphatase and hexosediphosphatase are depressed by insulin injection. However, a multiphasic pattern is observed in the changes of these gluconeogenic enzymes following insulin treatments when their activities are expressed as units/100 gm. body weight or unit/mg. protein. Insulin withdrawal causes immediate rise in gluconeogenic enzymes, particularly in the extramitochondrial activity of pyruvate carboxylase, and decreases in glucose-catabolizing enzymes which proceed at different rates.
Influence of Nutritional Factors on Prevalence of Diabetes
Authors: West Kelly M , Kalbfleisch John M
Published: December 2014

Twelve age-matched populations of eleven countries were tested by standardized methods to determine associations between prevalence of hyperglycemia and certain epidemiologic variables, including several nutritional factors. There were great differences among some of these populations in socioeconomic status, diet, adiposity, and race. Environmental and demographic circumstances varied widely and prevalence of diabetes differed as much as ten-fold. There was in general a positive association between prevalence of diabetes and dietary intake of fat and of sugar, and a negative association between prevalence of diabetes and total carbohydrate consumption; but some inconsistencies in these associations suggested that they may have been partly or completely coincidental. Prevalence of diabetes correlated well with serum cholesterol levels, both among and within populations. Thejnost impressive and consistent association in these studies was between prevalence of diabetes and fatness (as estimated by weight in relation to height). Both within and among countries and races, this association was observed to a high degree. Interracial differences in prevalence of diabetes were small when racial groups were matched for adiposity.

In a group of 1,645 subjects from the general population of Central America, those with abnormal glucose tolerance had a substantially higher prevalence of electrocardiographic abnormalities than those with normal tolerance.
Degradation of Porcine Insulin and Proinsulin by Rat Adipose Tissue
Authors: Challoner David R
Published: December 2014

Degradation of 6.95 × 10−10 M I-125 porcine insulin and proinsulin to TCA soluble radioactivity was assessed in intact and homogenized rat fat pieces and isolated fat cells, with and without Kunitz pancreatic trypsin inhibitor (KPTI), 50μg./ml. Fat cells degraded both substances more actively than fat pieces. Homogenization increased degradation rate in fat pieces but had no effect in fat cells, suggesting the most active degrading sites were readily available to substrate in the fat cell preparation. They, therefore, could be either intimately associated with the cell membrane or, alternatively, intracellular with the fat cell of necessity permeable to insulin. Insulin and proinsulin competed for degradation, and KPTI inhibited only proinsulin degradation. These results are consistent with an initial trypsin-like cleavage of proinsulin with subsequent common degradation pathways with insulin.
Cellular Localization of Gastrin in the Human Pancreas
Authors: Greider Marie H , McGuigan James E
Published: December 2014

Cryostat-cut sections of unfixed and formalin-fixed human pancreata obtained at autopsy were stained by the direct method with fluoresceinated antibodies to human gastrin I. The cytoplasm of a small population of cells in the islets of Langerhans exhibited a bright yellow-green fluorescence. Specificity of the inimunochemical reaction was indicated by a decrease in intensity of stain after preincubation of the fluoresceinated antibody with gastrin and after pretreating the section with nonfluoresceinated antibody-preparation. Immunological cross reactivity with cholecystokinin-pancreozymin was excluded by use of highly specific fluoresceinlabelled antibodies to human gastrin I which exhibit no binding of cholecystokinin-pancreozymin.

The presence of immunoreactive gastrin in the human pancreas was also demonstrated by radioimmunoassay measurements of pancreatic tissue extracts.

The gastrin-containing cells were selectively stained by the Hellerstrom-Hellman method, indicating that the gastrin cell of the pancreatic islet is the classical delta cell of Bloom (or A1 cell of Hellerstrom and Hellman).
Nonketoacidotic Hyperglycemia and Coma During Intravenous Diazoxide Therapy in Uremia
Authors: Charles M Arthur , Danjorth Elliot
Published: December 2014

Hyperglycemic hyperosmolar nonketoacidotic coma developed in a twenty-year-old female with uremia when treated for hypertension with intravenous diazoxide. Low circulating serum insulin concentrations were found in this patient as well as in four others with this syndrome, thus supporting the recent hypothesis that these concentrations of insulin are adequate to block lipolysis but insufficient to prevent hyperglycemia. In view of the recognized inhibitory effect of diazoxide on pancreatic insulin release and peripheral glucose nietabolism, it is recommended that patients receiving intravenous diazoxide be observed for possible severe disturbances of carbohydrate metabolism and resulting hyperosmolarity.
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.
Impotence and Diabetes: Studies of Androgenic Function in Diabetic Impotent Males
Authors: Faerman I , Vilar O , Rivarola M A , Rosner J M , Jadzinsky M N , Fox D , Lloret A Perez , Bernstein-Hahn L , Saraceni D
Published: December 2014

Androgenic function was studied in seven diabetics with sexual impotence and in five patients with paraplegia. Plasma concentration of testosterone was measured before and after administration of 5,000 U. of human chorionic gonadotropin (HCG). Steroid biosynthesis by testicular tissue was studied in vitro and testicular morphology was evaluated by light and electron microscopy. The diabetic patients were also evaluated neurologically. Motor conduction velocity, electromyography of the quadriceps and the function of urinary bladder were studied. Plasma concentration of testosterone was in the normal range in basal conditions in impotent diabetics (mean 578 ± 234 mμg./100 ml.) and paraplegics (mean 788 ± 184 mμg./ 100 ml.). After stimulation with HCG, impotent diabetics showed a mean value of 1,523 ± 314 mμg./100 ml. In vitro steroid biosynthesis by testicular homogenates of diabetics and paraplegics was normal. The morphology of the interstitial tissue was normal in patients with diabetes or paraplegia. Subcellular characteristics of Leydig cells were also normal. In the tubules, a marked hypospermatogenesis with desquamation of the germinal epithelium was observed in the two groups in all patients. Alterations of the motility of the bladder were seen in six diabetics and all paraplegics. Motor conduction velocity was abnormal in the diabetics. It is concluded that in our patients androgenic function was normal, and therefare impotence can not be attributed to hormonal deficieney.
Use of Jet Insulin Injection in Diabetes Mellitus Therapy
Authors: Cohn Major L , Chez Ronald A , Hingson Robert A , Szulman Aron E , Trimmer Michael
Published: December 2014

The insulin requirements of streptozotocin-induced glucose-intolerant rhesus monkeys were administered with a gas-driven jet, a spring-driven jet in the morning, and a needle and syringe in the afternoon, alternately for thirty days. The three technics of insulin administration were comparable in maintaining the carbohydrate balance of the monkeys. Compared to needle and syringe, jet injectors equate in the incidence of post-injection induration, incision, and leak or splashback. Rapidity, ease of administration, and maintenance of sterility appear to be advantages. Disadvantages of the jet injection include the initial cost and, in some brands, service. Furthermore, mixtures of different insulin types require premixing or the use of two separate jet insulin injections. Biopsy examination of needle and syringe injection sites compared to jet injection sites in these animals revealed no histologic differences.
On the Maximal Possible Rate of Ketogenesis
Authors: Flatt J P
Published: December 2014

The conversion of fatty acids to ketones is an energy-generating process. An evaluation of its quantitative significance on the energy metabolism of the human liver is presented. It is shown that in the decompensated diabetic state ketogenesis provides most of the energy used in this organ. Thus, under these conditions, ketogenesis appears to be limited by the rate of energy utilization in the liver. Since gluconeogenesis increases the energy expenditure in the liver, gluconeogenesis can be seen to have a permissive effect on ketogenesis. It is suggested that this interaction, at the level of the energy metabolism in the liver, explains why pathological rates of ketogenesis are found in metabolic situations where gluconeogenesis is very rapid.
Effect of Obesity on Insulin Sensitivity of Human Adipose Tissue
Authors: Davidson Mayer B , Karjala Robert G
Published: December 2014

Subcutaneous abdominal adipose tissue was removed from six normal weight patients (118–184 lb.) at laparotomy and six obese subjects (280–533 lb.) under local anesthesia and incubated in vitro. Glucose-C-14 incorporation into CO2, total lipids and glycogen were measured. Although insulin (10 mU./ml.) stimulated CO2 production from glucose in all twelve subjects (p < .001), the average increase was only 26.6 per cent (5.3 to 50.8). Radioactive glucose incorporation into total lipids was increased by insulin in eight of twelve subjects (average rise = 21.9 per cent; range, −45.5 to 107.1 per cent), but this failed to achieve significance. This small insulin effect on human adipose tissue reflects the experience of others. On the other hand, insulin-stimulated glycogen synthesis proved to be the most sensitive indicator of hormonal activity (mean rise = 231.9 per cent; range, 66.2 to 562.2 per cent). There was no significant difference in basal or insulin-stimulated glucose incorporation into CO2, total lipids or glycogen between the obese and normal weight subjects. The insulin effect on glycogen synthesis could not be correlated with either weight index or body fat in these twelve subjects. Basal conversion of glucose to CO2 was significantly correlated with these two measures of obesity (r = 0.6, p < .05). These data corroborate two other reports that obesity is associated with increased basal glucose metabolism by human adipose tissue in vitro. However, they fail to substantiate the postulate that adipose tissue of the obese is insensitive in insulin. These results and the fact that only approximately 5 per cent of basal or. insulin-stimulated glucose turnover in vivo involves adipose tissue suggest that insensitivity of the muscle mass and/or a circulating insulin antagonist should be more important in the insulin antagonism of obesity.
Defective Immunoreactive Insulin Secretion in the Acomys Cahirinus
Authors: Cameron Donald P , Stauffacher Werner , Orei Lelio , Amherdt Mylene , Renold Albert E
Published: December 2014

In vivo studies of immunoreactive insulin (IRI) secretion and electron microscopic studies of pancreatic morphology have been performed in the spiny mouse, acomys cahirinus. A defective IRI release was demonstrated in response to glucose 1.0 gm./kg., arginine 200 mg./kg., glucagon 1 mg./kg., isoprenaline 20 μg./kg., aminophylline 240 mg./kg. and dibutyryl cyclic AMP 60 mg./kg., administered intraperitoneally when compared to normal Swiss white mice. The defect appeared to involve both phases of IRI release. Electron microscopic evidence supported the concept of defective IRI release in this species. Of particular interest was the frequent occurrence in B cells of autophagic vacuoles comparable to those described for other cells undergoing secretory arrest. It is suggested that the defect of IRI release involves some basic mechanism concerned with the transport of insulin out of the B cell.
Metabolism of Glycosaminoglycans in Alloxan Diabetic Rats: I. Changes in Tissue Glycosaminoglycans
Authors: Malathy K , Kurup P A
Published: December 2014

The changes in glycosaminoglycans and lipids in the aorta, kidney, skin and retina in alloxan diabetic rats have been studied. Maximum increase in the total cholesterol occurred in the aorta and retina; the skin and kidney showed moderate increase. The increase in phospholipid was moderate in the skin, but less in the kidney, aorta and retina. Glycosaminoglycan concentration was highest in the aorta, while the retina contained moderate amounts. The kidney and skin showed much lower amounts. The changes in the different fractions of glycosaminoglycans in these tissues, fifteen days and two months after alloxan administration, have been studied. In the aorta and retina, the ratio of sulfated glycosaminoglycans to hyaluronic acid is normally high and decreases considerably in the alloxan diabetic rat. In the kidney also there is significant decrease in this ratio, but in the skin there is a decrease of both sulfated glycosaminoglycans as well as hyaluronic acid. The possible role of glycosaminoglycans in the development of cardiovascular complications of diabetes has been discussed.
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.
Glucose Intolerance During Decreased Physical Activity in Man
Authors: Lipman Richard L , Raskin Philip , Love Tommy , Triebwasser John , Lecocq Frank R , Schnure Joel J
Published: December 2014

Impaired glucose tolerance is a well documented consequence of absolute bedrest in man. Previous studies have shown a decrease in forearm glucose uptake during intravenous glucose infusion after fourteen days of bedrest. Bedrest is associated not only with physical inactivity but with a change in gravitational vector. This study was designed to examine the individual contributions of these factors to the glucose intolerance of bedrest. Thus, glucose tolerance tests were carried out in exercising subjects at bedrest and in rhesus monkeys immobilized in the vertical plane. Exercise in man improved glucose tolerance during bedrest, and vertically immobilized monkeys demonstrated significant glucose intolerance. It is concluded that the glucose intolerance of bedrest is a function of the decrease in physical activity.
Insulin and Proinsulin Conformation in Solution
Authors: Frank B H , Pekar A H , Veros A J
Published: December 2014

The physical chemistry of the insulin molecule in solution is reviewed. The nature of the self-association behavior is such that at physiological concentration levels insulin must exist as a monomer even in the presence of zinc. Analysis of the data on the interaction between zinc and insulin in solution leads to the conclusion that the zinc insulin complex formed has a conformation very similar to the x-ray structure of crystalline zinc insulin. Conformational studies on insulin and proinsulin support the following structural model—the insulin portion of the proinsulin molecule is in the same conformation as the free insulin molecule. Finally, studies indicate that the α-NH2 group on the A1 glycine of insulin is very important for biological activity.
Insulin Secretion Mechanisms and Glucose Metabolism in Isolated Islets
Authors: Ashcroft Stephen J H , Bassett John M , Randle Philip J
Published: December 2014

The in vitro effects of glucose and analogs of glucose on insulin secretion have been reinvestigated with rat and mouse islets. Curves relating rates of insulin secretion to glucose concentration were sigmoid with a Km of 6–8 mM and tending to Vmax at approximately 20 mM glucose. Mannose and glucosamine were the only analogs of glucose which stimulated secretion in the absence of glucose. Fructose, N-acetyl glucosamine and galactose (rat only) potentiated secretion at 2.5 or 5 mM glucose but not at 20mM glucose. Other analogs of glucose were inactive. Mannoheptulose inhibited glucose effects at all concentrations of glucose; glucosamine was inhibitory at 5 mM and 20 mM glucose. It is concluded that there may be quantitatively or qualitatively two distinct types of receptor mechanism in islets: (1) an initiator unit sensitive to effects of glucose, mannose, glucosamine, mannoheptulose and leucine and (2) a potentiator unit sensitive to effects of fructose, N-acetyl glucosamine and galactose (and also glucose and mannose?). Rates of glucose utilization measured in islets with [5·3H] glucose were linearly related to rates of insulin secretion with varying glucose concentrations, with mannoheptulose and with glucosamine. It is concluded that evidence currently available does not determine whether initiation of insulin secretion by glucose, mannose or glucosamine involves a direct effect of the sugar or of a metabolite.
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.