bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum Immunoreactive Insulin Levels During Glucose Tolerance and Intensive Islet Stimulation: Effect of Prednisone
Authors: Ryan Will G , Schwartz Theodore B , Nibbe Albert F
Published: December 2014

The effects of a potent glucocorticoid (prednisone) on hlood sugar and serum immunoreactive insulin (IRI) levels during glucose tolerance and intensive islet stimulation were studied in forty-two subjects whose glucose tolerance ranged from well-within-normal limits to frankly diabetic. The ability to maintain “normal” glucose tolerance under this added stress was not directly related to capacity for increasing serum IRI levels. “Diabetic” subjects were not more susceptible to degeneration of glucose tolerance after prednisone even though serum IRI levels increased little 01 even decreased in several subjects. The data make it difficult to directly relate the magnitude of serum IRI levels at the times measured to degree of glucose intolerance and suggest that other factors (possibly insulin resistance), as yet unknown, are operative.
Labeled Insulin Catabolism in Chronic Renal Failure and in the Anephric State
Authors: Corvilain J , Brauman H , Delcroix C , Toussaint C , Vereerstraeten P , Franckson J R M
Published: December 2014

The influence of the kidney in the catabolism of insulin was investigated by comparing the metabolic clearance rate of labeled insulin in control subjects, in patients with chronic renal failure and in anephric patients, both groups being treated for several months by iteral dialysis. The methodology involved the constant infusion (23 ng./kg./min.) of mildly iodinated (mean iodination degree inferior to 0.2 atom/molecule) I-125-insulin, the estimation of the plasma content in labeled insulin by chromatoelectrophoresis, and the use of an analog and a digital computer for the calculation of the metabolic clearance rate.

In patients with chronic renal insufficiency and in anephric patients a marked reduction of the metabolic clearance rate (MCR) was observed and the extent of this reduction was comparable in these two groups of patients.

The findings confirm the part played by the kidneys in the metabolism of insulin anddemonstrate that in serious chronic nephropathies, the kidneys have completely lost their ability to catabolize insulin. They also provide an explanation for the reduced insulin requirements observed in certain cases of diabetes complicated with a nephropathy.
Relationship of Blood Acetoacetate and 3-Hydroxybutyrate in Diabetes
Authors: Stephens Jennifer M , Sulway M J , Watkins P J
Published: December 2014

The ratio of blood ketone bodies 3-hydroxybutyrate to acetoacetate, once thought to be fairly constant, has been shown to vary from 0.6:1 to 4.8:1. In untreated, ketoacidotic patients, it is directly related to the plasma free fatty acid level. Administration of insulin lowers the ratio because the fall of blood 3-hydroxybutyrate occurs earlier and more rapidly than that of acetoacetate. During the treatment of ketoacidosis there is usually an initial increase of the acetoacetate which may persist at a high levelfor several hours despite improvement of the patient and falling 3-hydroxybutyrate and glucose levels.
Severe Diabetic Ketoacidosis (Diabetic “Coma”): 482 Episodes in 257 Patients; Experience of Three Years
Authors: Beigelman Paul M
Published: December 2014

There were 340 episodes of severe diabetic ketoacidosis in 257 patients, July 1, 1965 to June 30, 1968. Fatality in thirty-two cases was associated with significantly elevated admission serum glucose, urea nitrogen, osmolality and age. Major associated causes of death were infection and myocardial infarction. Twenty episodes of acute pancreatitis, with only two deaths, demonstrated severe morbidity and marked elevation of serumglucose and urea nitrogen. Fourteen of the twenty occurred in alcoholics. There were eleven episodes in ten pregnant women, with one maternal and seven fetal deaths. Admission serum potassium, recorded in 336 episodes, was markedly elevated in 22 per cent and decreased in 4 per cent. Including all multiple admissions, there were 482 episodes; forty had hypoglycemic reactions, none with fatality or severe morbidity. Nine cases of nonketotic hyperosmolar coma, with five deaths, demonstrated very high admission serum glucose, urea nitrogen, and osmolality levels.
Sexual Dysfunction in Diabetic Females
Authors: Kolodny Robert C
Published: December 2014

Problems of sexual function in male diabetics are well-known, but studies have not been previously published documenting the incidence of such distress in diabetic females. One hundred and twenty-five diabetic women and 100 nondiabetic women between the ages of eighteen and forty-two were interviewed to determine the incidence of sexual dysfunction in these two groups. Forty-four of the 125 diabetic women (35.2 per cent) and six of the 100 nondiabetic women (6 per cent) reported complete nonorgasmic function in the preceding year, a difference significant at the P < .01 level. The appearance of sexual dysfunction in diabetic women correlated strongly with duration of diabetes, but there was little association with age, insulin dose, or such complications of diabetes as neuropathy, retinopathy, nephropathy or vaginitis. The term “secondary orgasmic dysfunction” is proposed for cases where impaired sexual response is felt to be on an organic basis, but appears only after a phase of normal sexual functioning.
Effect of High Protein Feeding on Gluconeogenesis in Rat Liver
Authors: Eisenstein Albert B , Strack Inge
Published: December 2014

Although alanine (A) is the major substrate for hepatic gluconeogenesis, it is utilized less effectively than pyruvate or lactate, thus suggesting that glutamic alanine transaminase (GAT) regulates A conversion to glucose. To test this hypothesis incorporation of A and pyruvate into glucose, glycogen and protein by isolated livers of rats fed a high protein (HP) diet was determined and compared with that by liver of normally fed animals. Effect of HP feeding on transport of α-aminoisobutyric acid (AIB), a nonutiliz-able amino acid, into liver was investigated. Liver GAT and phosphoenolpyruvate carboxykinase (PEPCK) activities were determined. HP feeding produced a twofold increase in conversion of A to glucose when perfusate A-concentration was physiological (0.5 mM) and when excess A was present. Liver glycogen synthesis from A was less than that of glucose and was unaffected by HP feeding. Incorporation of A into protein by control and HP livers was negligible. Hepatic conversion of pyruvate to glucose was markedly enhanced by the HP diet whereas glycogen synthesis from pyruvate was limited and not affected by HP feeding. AIB transport by liver of HP fed rats was double that of control liver. Liver GAT and PEPCK activities were greatly increased by HP feeding.

Increased gluconeogenesis in HP liver at physiological and excess perfusate A concentrations indicates that amino acid transport and transamination are stimulated since other investigations have demonstrated that at low A levels transport is rate limiting and at high A concentrations, transamination controls gluconeogenesis. Furthermore, we observed increased AIB transport and elevated GAT activity in HP liver, thus it is clear that the GAT does not alone control conversion of A to glucose. Increased gluconeogenesis from pyruvate and elevated PEPCK activity were found suggesting that HP feeding stimulates conversion of pyruvate to phosphoenolpyruvate. The effects produced by the HP diet also occur after glucagon administration thus HP feeding probably influences gluconeogenesis by stimulating glucagon secretion.
A Case of Growth-onset Diabetes Presenting with Proliferative Retinopathy
Authors: Strachan I M
Published: December 2014

A sixteen-year-old boy's presenting feature of diabetes was visual disturbance in the left eye due to proliferative diabetic retinopathy. This case is thought to be unique in a diabetic patient in this age group.
Pancreatic Islet Levels of Citrate Under Conditions of Stimulated and Inhibited Insulin Release
Authors: Hellman Bo , Idahl Lars-Ake
Published: December 2014

The possible significance of citrate for insulin release was elucidated by measuring the levels of this metabolite in isolated pancreatic islets from obese-hyperglycemic mice and their lean litter mates. The amount of islet citrate depended on the extracellular glucose concentration but was not affected by the insulin secretagogues, glibenclamide or dibutyryl cyclic-3,5-AMP. Increased β-cell levels of citrate do not necessarily result in stimulation of insulin release, as shown by the increased amounts of citrate in islets exposed to epinephrine. Octanoate (5 mM) had no effect on the level of citrate in islets exposed to 0.6 mg./ml. glucose. In the presence of 3 mg./ml. glucose, octanoate significantly depressed the citrate level. It seems unlikely that the citrate molecule has the important role in controlling insulin release that has previously been suggested.
Acute Effects of Human Chorionic Somatomammotropin on Insulin and Glucagon Release in the Isolated Perfused Pancreas
Authors: Laube Heiner , Fussgänger Rolf D , Schröder Karl E , Pfeiffer Ernst F
Published: December 2014

Insulin and glucagon release from the isolated perfused pancreas of rats was measured following administration of human chorionic somatomammotropin (HCS). In the presence of low glucose levels there is a significant acute but short release of insulin and glucagon following HCS, which is not sustained despite continuous HCS infusion. The magnitude of HCS-induced insulin and glucagon release is closely related to the glucose concentration of the perfusion medium. At high glucose levels of 11 mM. there is no significant action on insulin or glucagon output by HCS. The short peaks of insulin and glucagon release are probably due to an HCS-induced membrane effect. The acute effects on α and β cells of the endocrine pancreas may indicate certain relationships between glycohomeostasis and HCS serum levels in pregnancy.
Inhibitory Effect of Diphenylhydantoin on the Diabetogenic Action of Alloxan in the Mouse
Authors: Mennear John H , Gossel Thomas A
Published: December 2014

The effect of the pretreatment of mice with diphenylhydantoin (DPH) on the development of alloxan diabetes was studied. DPH, in intraperitoneal doses of 20 to 45 mg./kg., administered one hour prior to alloxan, was found to prevent the development of alloxan (75 mg./kg., intravenously) diabetes. Administration of DPH after alloxan had no effect. The initial hyperglycemie response to alloxan (measured forty-five minutes post-alloxan) was potentiated by DPH pretreatment. Intravenous glutathione, administered one minute prior to alloxan, inhibited both the initial and chronic hyperglycemia produced by alloxan. A structural similarity between DPH and alloxan suggests that DPH may be protecting pancreatic beta cell binding sites from alloxan.
Nineteen Hundred Twenty-One in Toronto
Authors: Best Charles H
Published: December 2014

A brief account is presented of the events from the time Charles H. Best met Frederick C. Banting in 1920 until the early days of 1922 when the extract of beef pancreas was injected by the partners to each other and was sent to the Toronto General Hospital for use of the first patients. Nineteen hundred twenty-one began gently with some teaching and little practice for Fred Banting. Charles Best was busy with his final year in physiology and biochemistry and with research on experimental diabetes.

The beginning of the insulin research was well organized. The partners were happy to be working alone. The first injection of insulin on July 30, to Dog No. 410, gave a very definite result but caused little excitement. During the first two weeks of August, however, several dramatically successful tests were made on Dog No. 408, and the partners were certain that they could make consistently a very potent extract containing the internal secretion of the pancreas. The excitement increased with each new finding—solubility in acid alcohol, destruction by alkali, by trypsin and by heat, the phenomenal improvement in the clinical condition of the dogs, the prolonged extension of life—all these points made Banting and Best certain that human patients would respond similarly, as was indeed the case.

The reports in Toronto in November and in New Haven in December were enthusiastically received. Insulin had been launched.
Insulin and Glycogen Synthase
Authors: Larner Joseph
Published: December 2014

The present status of the molecular nature of the enzyme glycogen synthase from rabbit skeletal muscle is reviewed. It is shown that per 90,000 Dalton subunit there are six phosphorylatable sites and six sulfhydryl groups. No pyridoxal phosphate is present. The enzyme has a hexagonal subunit visible in the electron microscope which associates to tetramers and higher forms as well.

Insulin brings about a shift from dependent (D) to independent (I) form in all sensitive tissues. This is accompanied by a shift in the kinase from an I to D form. Although under certain conditions a decreased cyclic AMP concentration may be observed, under other conditions no change is observed. The combination of an altered kinase sensitivity to cyclic AMP together with a potential decrease in cyclic AMP concentration suggests a decreased kinase activity and explains the D to I shift in synthase. The question of a new intermediate related to cyclic AMP whose formation is stimulated by insulin is introduced as a hypothesis.
Clinical Aspects of Insulin–Antigenicity
Authors: Schlichtkrull J , Brange J , Hein Christiansen Aa , Hallund O , Heding L G , Jørgensen K H
Published: December 2014

Conventional insulin such as that used for therapy displayed a series of bands in polyacrylamide disc-gel electrophoresis, representing monodesamido-insulin, insulin corresponding to Sanger's formula, the intermediates of proinsulin, arginine insulin, insulin ethyl ester, proinsulin, etc. Separation according to molecular size was achieved by molecular sieving in Sephadex columns; anion-exchange chromatography yielded essentially pure insulin. When injected as a neutral solution, this monocomponent insulin was nonimmunogenic in rabbits, while the isolated protein contaminants elicited insulin antibody formation, which explains the immunogenicity observed with conventional recrystallized insulin. The values of insulin binding to serum IgG were determined by a standard electrophoretic procedure, with a fixed concentration of added 125I-labeled insulin. The values of total serum IRI were determined after acid ethanol extraction. The IgG binding and the total IRI were determined sequentially in sera from patients from the beginning of treatment with conventional insulin preparations. In the course of a few months, both parameters became considerably elevated. Practically no elevation was observed in sera from patients after treatment with monocomponent porcine Lente insulin, there was little or no antibody response, and the total serum IRI remained normal.
Immunogenicity of Insulin
Authors: Root Mary A , Chance Ronald E , Galloway John A
Published: December 2014

Highly purified bovine and porcine insulins (single component insulin) did not produce antibodies in rabbits, and the highly purified porcine insulin was less immunogenic in diabetic patients than USP porcine insulin. In rabbits one porcine high molecular weight fraction (peak A) and two bovine high molecular weight fractions (peak A and peak B) separated from USP insulin by Sephadex chromatography were immunogenic, producing increases in the amount of 125I-labeled single component insulin bound by the serum. Both peaks (A and B) derived from bovine insulin produced significantly greater insulin binding in rabbits than did the same peaks derived from porcine insulin. In diabetic patients single component porcine insulin produced less binding of insulin to the serum than did USP insulin.
Current Unsolved Problems in Diabetes Management
Authors: Fajans Stefan S
Published: December 2014

Two unsolved problems in diabetic management are discussed. One involves the question whether “normalization” of blood glucose remains a desirable goal in the treatment of the diabetic patient in the hope of preventing, ameliorating or postponing the macroangiopathic, microangiopathic and neurological changes associated with diabetes mellitus. Some findings are reviewed which support or refute the concept that there is a possible or probable correlation between derangements of insulin secretion and attendant abnormalities in intermediary metabolism and the chronic complications of diabetes mellitus. A conclusive answer to this question is unlikely to evolve until therapy is devised which will continuously achieve complete normalization of hormonal and metabolic abnormalities.

On the premise that the nature of the diet may have an effect on the development of some complications, the second problem discussed is the optimum composition of the diet which will be most beneficial to the diabetic patient from a prophylactic point of view.
Insulin Action at the Molecular Level: Facts and Speculations
Authors: Krahl M. E.
Published: December 2014

Insulin is a hormone that is itself anabolic and is required for the action of other major mammalian hormones that promote growth. Three groups of molecules possibly related to this anabolic function are considered: (1) molecules that relate to the structure of membranes and the initiation of insulin action, including insulin receptors; (2) molecules (such as cyclic nucleotides and cations, e.g. K+ and Mg++) that are potentially concerned with transmission and amplification of information from the plasma membrane to subcellular functional units; (3) molecules that may contribute directly to development of juvenile or maturity-onset diabetes. Two new concepts are proposed: First, the receptor for insulin occupies a locus on the plasma membrane coupled to Mg++-activated (Na+ + K+). ATPase; hormone activation stimulates ATPase activity. As a result of the activation of the membrane ATPase enzyme system by insulin, concentrations of K+ and Mg++ increase at critical intracellular loci; these ions then serve as “second messengers.” The second new concept is that the genetic abnormality in human diabetes mellitus lies in a single or multiple enzyme defect that leads to accumulation of a fragment from growth hormone. One such fragment is known to inhibit glucose uptake and fatty acid synthesis.
Profile of Insulin Release Due to Intrapancreatic Glyburide Infusion
Authors: Colwell A R , Zuckerman Leon
Published: December 2014

Intrapancreatic glyburide infusion in dogs (0.02 mg. per kg. of body weight) for five minutes provoked immediate, marked insulin release into the portal venous blood. Compared to control animals, the normal intrinsic insulin levels were exaggerated at intervals of approximately eighty minutes. Lack of immediate hypoglycemia suggests that the insulin release is merely secondary in contributing to the anti-diabetic property of this agent. An amount of tolbutamide fifty times as great caused a weak, delayed insulin response. The delayed blood glucose response is probably caused by the combined action of glyburide and circulating insulin.
Lack of Ketosis in Lipoatrophic Diabetes
Authors: Kikkawa Ryuichi , Hoshi Mitsuru , Shigeta Yukio , Izumi Kanji
Published: December 2014

Several metabolic studies wece performed on a thirty-year-old Japanese woman with lipoatrophic diabetes. The fasting serum levels of insulin were high, and the insulin response to glucose ingestion was subnormal. The serum growth hormone levels were normal.

Lipolytic and ketonemic stimuli such as starvation and epinephrine injection failed to increase the serum concentrations of nonesterified fatty acids (NEFA) and ketone bodies. The absence of ketonemia was attributable to the lack of substrate delivered from adipose tissue.
Comparison of the Inhibitory Effects of Diphenylhydantoin and Diazoxide Upon Insulin Secretion from the Isolated Perfused Pancreas
Authors: Levin Seymour R , Grodsky Gerold M , Hagura Ryoko , Smith Desmond
Published: December 2014

Both diazoxide and diphenylhydantoin have been shown to cause hyperglycemie in man and to inhibit insulin secretion in vitro. The effects of these two drugs upon the response to 300 mg./100 ml. glucose were contrasted in the isolated, perfused rat pancreas. Similarities: Both drugs inhibited within seconds. At high concentrations (75 μg./ml.) of either drug, 95 to 100 per cent inhibition occurred. Upon withdrawal, return of secretion was rapid. Differences: During constant (five- and twenty-minute) infusions of diazoxide (10 to 75 μg./ml.), there was an initial fall in secretion and then an “escape” toward pre-inhibition levels; after diazoxide there was a postinhibitory overshoot. In contrast, five-minute infusions of diphenylhydantoin (5 to 75 μg./ml.), and twenty-minute infusions of 25 to 75 μg./ml., though causing comparable levels of initial inhibition, did not cause escape or postinhibitory overshoot. However, an incompletely inhibitory concentration of diphenylhydantoin (10 μg./ml.), given for twenty minutes, was followed by this overshoot.

Computer simulation, based on the compartmental-quantal model, suggested that diphenylhydantoin inhibits both secretion from a labile insulin compartment and provision of insulin and/or precursor to this compartment. Lower, partially inhibitory concentrations (i.e. 10 μg./ml.) of diphenylhydantoin might allow for some provision to proceed, and thus a postinhibitory overshoot would occur. The escape and overshoot noted with all inhibitory levels of diazoxide, when compared with the simulations, suggested that this drug may act primarily to inhibit a late step in the provisionary phase.
Effect of Long-chain Triglyceride on Human Insulin Secretion
Authors: Carroll Kevin F , Nestel Paul J
Published: December 2014

The responses of blood glucose and plasma free fatty acid (FFA), triglycéride (TG) and immunoreactive insulin concentrations to the oral and intravenous administration of long-chain TG have been measured in normal subjects.

A TG emulsion and an aqueous solution of glycerol were each infused intravenously over five hours on different days in six subjects. Glycerol infusion produced no measurable effect. The TG infusion did not induce changes in plasma insulin and blood glucose concentrations despite increases in plasma FFA and TG levels.

Eight subjects ingested safflower oil on one occasion and water on another. Oil ingestion caused an early and significant increase in the plasma insulin concentration, which preceded any increases in plasma FFA and TG concentrations. Blood glucose levels were unchanged.

In six additional subjects, the ingestion of a safflower oil emulsion, in contrast to the unemulsified oil, led to earlier and larger increases in plasma FFA and TG concentrations. Despite differences in rates of TG absorption, there was no difference in the pattern of plasma insulin and blood glucose responses to emulsified or unemulsified oil.

Therefore only the oral, but not the intravenous, administration of TG stimulated insulin release, which was not related to changes in plasma FFA and TG levels. The insulin response to ingested TG may therefore reflect the release of gastrointestinal hormones, such as pancreozymin, which in turn stimulates the pancreatic islets.
Hyperglycemia in Washoe and Northern Paiute Indians
Authors: Bartha Gregory W , Burch Thomas A , Bennett Peter H
Published: December 2014

The prevalence of hyperglycemia in two American Indian tribes, the Washoe and Northern Paiute, was evaluated by determining the number of individuals aged fifteen years and older with a history of concurrently treated diabetes or with a plasma glucose level of at least 160 mg./100 ml. (Auto Analyzer) two hours after a 75-gm. glucose equivalent load. One hundred and twelve Washoe Indians, representing 74.2 per cent of the Washoe study population, and 131 Paiute Indians, 60.6 per cent of the Paiute study population, were examined. The prevalence of hyperglycemia was 10.7 per cent for the Washoe and 11.5 per cent for the Paiute group. These rates, when adjusted for age and sex, did not differ significantly from each other or from that reported for the Cocopah Indians. The adjusted rates for these three tribes were significantly lower than the adjusted rate for the Pima. In both the Washoe and Paiute populations, the prevalence of hyperglycemia increased with age, but was not related to parity.
Effect of Time on the Prevalence of Diabetes in the Urban African of Rhodesia
Authors: Wicks A C B , Castle W M , Gelfand M
Published: December 2014

A diabetes survey was conducted in the same African urban township as one done eleven years previously, together with a further survey in a rural area. In the urban survey the prevalence rate rose insignificantly from 0.10 per cent to 0.28 per cent, while no diabetes was discovered in the rural study. A minimal increase of new diabetics was seen during the same period in both the medical wards and obstetric unit, but the disease has not reached the proportions seen either in Europeans or indeed in Africans from certain parts of Southern Africa. A lack of coronary artery disease in diabetes is emphasized. These findings are discussed in the light of experience elsewhere, and some etiologic factors are suggested.
Glucose-mediated Insulin Release: 3′,5′ cAMP Phosphodiesterase
Authors: Bowen Vyuyan , Lazarus Norman R
Published: December 2014

Cyclic nucleotide phosphodiesterase from isolated mouse islets of Langerhans has been investigated and characterized. The enzyme has a pH optimum of 8.5 and is magnesium dependent, 10 mM. magnesium causing a fivefold increase in V max. Calcium is without effect on the enzyme. It is inhibited by theophylline and parachloromercuribenzoate. Glucose, has no effect on the activity of the enzyme. Tolbutamide at concentrations equivalent to those found under clinical conditions is a noncompetitive inhibitor of the enzyme.
Serial Postprandial Plasma Insulin Levels in 117 Subjects With and Without Diabetes
Authors: Tchobroutsky Georges , Kopf Armand , Eschwege Eveline , Assan Roger
Published: December 2014

Fifty-eight nondiabetic subjects and fifty-nine diabetic patients were studied to determine the pattern of postprandial plasma insulin levels. In nondiabetic subjects, including both healthy and “medical” (ill) patients, plasma insulin levels after lunch were higher in obese than in nonobese subjects but did not depend upon sex or age. The maximal value occurred forty-five to sixty minutes after the beginning of the meal.

When obese and nonobese subjects were analyzed separately, no significant difference in plasma insulin values was observed between nondiabetic subjects and hyperglycemic diabetic patients not receiving insulin. A delayed insulin response occurred in obese diabetics. Obese untreated patients had higher plasma insulin levels than nonobese untreated and obese treated persons. Subjects receiving long-term oral treatment and untreated, nonobese diabetics had no difference in mean plasma insulin levels.

Portal vein sampling in four maturity-onset diabetic subjects revealed low and sluggish insulin secretion after food intake.

Insulin-treated diabetic patients without insulin antibodies had significantly higher plasma insulin levels than nondiabetic subjects one and two hours after the beginning of the meal. Patients receiving short-acting insulin just before lunch had higher postprandial plasma insulin values and lower blood glucose levels than diabetic subjects taking long-acting or intermediate insulin.
Serial Postprandial Blood Glucose Levels in 309 Subjects With and Without Diabetes
Authors: Kopf Armand , Tchobroutsky Georges , Eschwege Eveline
Published: December 2014

The pattern of postprandial blood glucose levels was studied in 110 nondiabetic subjects and 199 diabetic patients. In nondiabetic subjects, including both healthy and “medical” (ill) patients, the maximal increase of blood glucose levels (BG) was observed forty-five to sixty minutes after the beginning of the meal, and the lowest values were seen at the second hour. The increase in blood sugar did not depend upon sex or weight, but was dependent upon age. The regression line between age and the 120 minute BG level is described by the equation: second hour BG = 0.603 × years + 89.4.

Diabetic patients not treated with insulin had higher BG levels than nondiabetic individuals. There was no significant difference between untreated diabetics and those receiving sulfonylurea, biguanide or biguanide plus sulfonylurea, except that the sulfonylurea-treated group had slightly higher BG values at 120 minutes. Postprandial blood glucose values were high in insulin-treated diabetic patients, but the more daily injections the patients received, the lower was the BG. Blood glucose decline was observed earlier when patients were given an injection of short-acting insulin just before the meal. These results were confirmed in an additional study of sixteen patients who were tested three times with the three kinds of insulin treatment.

Comparison with nondiabetic subjects may facilitate identification of criteria for control of diabetes in the postprandial state both with and without insulin treatment. This study also indicates that with any of the treatments some diabetic subjects may have postprandial glucose homeostasis similar to that of nondiabetic subjects.
Epidemiologic Studies of Serum Glucose Levels among Micronesians
Authors: Reed Dwayne , Labarthe Darwin , Stallones Reuel , Brody Jacob
Published: December 2014

Data from epidemiologic studies of Chamorro and Palauan populations of Micronesia were analyzed for associations of serum glucose levels with other characteristics of the population.

The frequency distribution patterns of serum glucose levels were similar to those reported for large United States populations, being unimodal and slightly skewed toward higher values.

Analysis by geographic subgroups showed differences in age- and sex-specific mean serum glucose levels, and in prevalence ratios of hyperglycemia. The general tendency was for the higher values to occur among the subgroups living in the relatively modern areas, as indicated by measures of education, occupation, sociocultural attitudes, and nutritional intakes of a high fat “Western type” diet.

Correlation analysis of individual characteristics indicated that serum glucose levels were positively associated with age, blood pressure, serum cholesterol and triglyceride levels, and body weight. There was no consistent association with electrocardiogram abnormalities, an inventory of symptoms, cigarette use, or with sociocultural measures of education, occupation, traditional attitudes, and residential mobility.

The over-all implication was that high serum glucose levels, high serum lipid levels and obesity were interrelated within these Micronesian populations.
Effect of Phenformin on Water and Glucose Transport Across Isolated Human Ileum
Authors: Wingate D L , Hadley G D
Published: December 2014

The effect of phenformin on the uptake of glucose and water by isolated full-thickness sheets of human ileum has been studied. A significant decrease in mucosal glucose uptake was found, and significant glucose translocation to the serosal surface was abolished. This was accompanied by a proportional decrease in the production of lactate and in the net transport of water across the tissue. The magnitude of the observed changes does not support the hypothesis that overt glucose malabsorption is of significance in the therapeutic action of phenformin but confirms previous observations that the kinetics of absorption of a glucose load may be altered.
Do the Oral and Intravenous Glucose Tolerance Tests Provide Similar Diagnostic Information in Patients with Chemical Diabetes Mellitus?
Authors: Olefsky Jerrold M , Farquhar John W , Reaven Gerald M
Published: December 2014

In order to evaluate the diagnostic reliability of the oral glucose tolerance test (OGTT) and the intravenous glucose tolerance test (IVGTT), the results of these two teats have been-compared both to each other as well as to a third test of carbohydrate tolerance termed the pancreatic suppression test (PST), in forty-five subjects. When results of the IVGTT and OGTT are compared, there is a 40 per cent incidence of discordance in the diagnosis of diabetes mellitus. There is no significant correlation between the results of the PST and the IVGTT, but a significant correlation is obtained between results of the PST and the OGTT (P < 0.01). Furthermore, the PST could not detect differences between patients classified as normal or diabetic on the basis of the IVGTT, but differences could be detected between subjects divided into diabetic or normal on the basis of the OGTT (P < 0.001). Although neither test is an ideal diagnostic tool, our results suggest that the OGTT is more meaningful than its counterpart in estimating the efficiency of glucose disposal in patients with mild abnormalities of glucose tolerance.
Failure of Induction of Liver Microsomal Enzymes by Tolbutamide in Maturity-Onset Diabetics
Authors: Redman D R , Prescott L F
Published: December 2014

Plasma tolbutamide half-life was measured in nine previously untreated mature onset diabetics before and after a minimum of two weeks treatment with 1.0 to 1.5 gm. of tolbutamide daily. The tolbutamide half-life was shortened in six patients, but the mean reduction in mean half-life from 5.7 to 5.3 hours was not statistically significant. Five patients then took phenobarbital, 60 to 90 mg. daily, for two weeks. There was no further reduction in mean tolbutamide half-life. Self-induced stimulation of tolbutamide metabolism is unlikely to be an important factor in the secondary failure of treatment of diabetics with this drug.
Autonomic Nervous System and Diabetes: Histological and Histochemical Study of the Autonomic Nerve Fibers of the Urinary Bladder in Diabetic Patients
Authors: Faerman Isaac , Glocer Leticia , Celener David , Jadzinsky Mauricio , Fox Dora , Maler Mario , Alvarez Enrique
Published: December 2014

Reports on the histologic aspects of the autonomic nerves in diabetics are infrequent. This investigation was carried out to study histologically and histochemically the autonomic nerve fibers of the urinary bladder wall in ten diabetic patients. Of the five subjects examined by biopsy, four showed damage of nerve fibers; absence of cholinesterase activity was the only finding in the fifth patient who had chemical diabetes.

In four autopsies we found alterations in all the cases. The lesions appeared as beaded or spindle-shaped fibers or small vacuolated or uniformly thickened fibers. The most severe cases exhibited fragmentation of the fibers.

Histochemical analysis demonstrated absence of cholinesterase activity in the muscle, in all cases, and absence or decrease of such activity in the nerves in all but one case. Similar studies performed on eight nondiabetic subjects revealed no anatomic or histochemical lesions.

The findings lead to the hypothesis that diabetic neuropathy injures the biochemical phase ofthe myelin sheath in the first stage and the nerve fibers later. No previous reports on the subject here studied could be found in the literature.
Action of Growth Hormone and Thyroxine on Aortas of Hypophysectomized Dogs
Authors: Brosnan Margaret E , Sirek O V , Sirek Anna , Przybylska Krystyna
Published: December 2014

Young dogs were surgically hypophysectomized and maintained for eleven weeks postoperatively with age-matched normal controls. For three weeks prior to sacrifice, four hypophysectomized dogs were given daily injections of bovine growth hormone (GH, 0.2 mg./kg.) and another four were given daily injections of thyroxine (T4, 5 μg./ kg.). Aortas were removed, cleaned of adventitia and divided into three segments: arch, thoracic and abdominal. Each portion was analyzed for collagen, elastin, deoxyribonucleic acid (DNA), calcium, total mucopolysaccharides (MPS), hyaluronic acid (HA), heparan sulfate (HS), dermatan sulfate (DS) and chondroitin sulfate (GS). The arch and thoracic aortas of normal animals were found to contain more DNA, CS and elastin but less collagen than the abdominal aorta. Removal of the hypophysis resulted in an overall increase in elastin and DNA content and caused a decrease in all sulfated MPS. Administration of either CH or T4 to hypophysectomized dogs had a profound effect on the majority of constituents in all segments of aorta. GH returned the content of elastin, DS and CS toward normal in at least two of the three aortic segments. T4 returned the content of DNA, DS and CS toward normal in all segments. Moreover, T4 treatment caused significant reductions in collagen and HA contents of thoracic and abdominal segments. These results indicate that: (1) the composition of normal aorta varies with the segment studied; (2) the composition of the aorta is markedly affected by hypophysectomy, CH and T4 treatment; and (3) individual aortic segments show differential sensitivity to a given hormone.
Evaluation of the Role of Exogenous Insulin on Phasic Insulin Secretion
Authors: Grodsky Gerold M , Fanska Rudy , Schmid Florence G
Published: December 2014

The possibility that insulin-induced feedback inhibition was responsible for the phasic release of insulin during continuous stimulation was investigated in the in vitro perfused rat pancreas. Continuous perfusion with selected concentrations of glucose (110 mg./100 ml.) ortolbutamide (300 μg./ml.) produced the characteristic initial rise and fall of insulin secretion; there was no rebound to high secretion rates during the later periods of stimulation with either agent. Rat insulin, perfused in a variety of patterns to simulate both early and steady state levels of endogenous insulin secretion, neither obliterated nor significantly affected the initial spike of endogenous insulin release elicited by either glucose or tolbutamide. There was no evidence of dampened oscillation or delayed inhibition by exogenous insulin. Results indicate insulin-induced feedback inhibition is not responsible for phasic insulin secretion; the previoussuggestions that this phenomenon reflects a substrate-induced feedback inhibition or a threshold-sensitive packet storage system are viable possibilities.
Collagenolytic Activity of Gingivae From Alloxan-Diabetic Rats
Authors: Ramamurthy N S , Zebrowski E J , Golub L M
Published: December 2014

Gingivae from both control and alloxan-diabetic rats exhibited collagenolytic activity in tissue culture. The alloxan treatment, however, increased the collagenase activity of the cultured tissues. This effect may account for the increased urinary excretion of hydroxyproline, the altered collagen metabolism of gingivae, and the development of osteoporosis of the mandible in alloxan-diabetic rats demonstrated in our laboratory previously.3,4
Xylitol Absorption in Healthy Men
Authors: Asano Takashi , Levitt Michael D , Goetz Frederick C
Published: December 2014

Xylitol absorption from the human intestinal tract was studied directly, by aspiration and analysis of ileul contents after ingestion of xylitol (5 to 30 gm.) mixed with glucose anda nonabsorbable marker, polyethylene glycol. Studies in five healthy subjects showed that xylitolabsorption ranged from 49 to 95 per cent. Chronic xylitol administration (30 gm, daily for two tothree weeks) did not alter significantly the rate of xylitol absorption. Neither symptoms nor laboratory abnormalities were observed following chronic xylitol ingestion.

Nearly complete intestinal absorption must be taken into account in considering the usefulness of xylitol in the diet, since untoward responses to intravenous xylitol infusions have been reported.
Diurnal Variation in Glucose Tolerance and in Insulin Secretion in Man
Authors: Carroll Kevin F , Nestel Paul J
Published: December 2014

The changes in blood glucose and plasma free fatty acid (FFA), insulin, and human growth hormone (HGH) concentrations in response to oral and intravenous glucose and intravenous insulin were measured at 7 a.m. and 7 p.m., on both occasions after a ten hour fast, in thirteen normal males and two juvenile diabetics.

Basal concentration of plasma FFA was lower and that of plasma insulin higher in the morning than in the evening. Blood glucose and plasma HGH levels did not differ at these times.

In the normal subjects, glucose tolerance was diminished and plasma insulin response was delayed in the evening. The delay was significantly less with intravenous glucose than with oral glucose. When compared with the usually accepted criteria for diagnosis of diabetes mellitus, the normal subjects responded in the evening as mild diabetics.

Two juvenile-onset diabetics, who had virtually no increase in plasma insulin concentrations after ingestion or injection of glucose, showed no diurnal variation in glucose tolerance.

No diurnal variation was seen in the blood glucose response to intravenously injected insulin or in the plasma clearance rate of insulin; these findings suggest that impairment in glucose tolerance in the evening is due to diminished early insulin response to glucose, rather than to abnormal handling of glucose or insulin.

The effect of tolbutamide, phentolamine, and theophylline on the diurnal variation of glucose tolerance was studied. In four subjects, intravenous injection of tolbutamide induced a greater insulin response and a greater fall in the blood glucose concentration in the morning than in the evening. The disappearance rate of intravenously injected glucose and both early and delayed insulin responses to the glucose were enhanced to a much greater degree in the morning than in the evening by the simultaneous intravenous injection of tolbutamide. Intravenous infusion of phentolamine, an alpha-adrenergic blocking agent, in five subjects failed to influence responses to intravenous injection of glucose. Intravenous infusion of theophylline, which inhibits cyclic 3′5′-adenosine monophosphate phosphodiesterase activity, in five subjects potentiated the plasma insulin response to intravenous glucose in the evening but not in the morning; the substance did not influence the disappearance rate of glucose.
Insulin Secretion in the Premature Infant: Response to Glucose and Amino Acids
Authors: Grasso S , Messina A , Distefano G , Vigo R , Reitano G
Published: December 2014

Serum insulin was measured in fifty-one premature infants in the first twenty-four hours of life following the administration of glucose, a mixture of amino acids, or glucose with an amino acid mixture. Infusion of glucose (1.25 gm.) caused a rapid increase of blood glucose and a small rise in serum insulin. The amino acid mixture (2.5 gm.) produced, on the contrary, a rapid and marked increase of serum insulin but only a slight rise of blood glucose. When the dose of the amino acid mixture was halved, rise of serum insulin and blood glucose was small. Combining the reduced dose of amino acid mixture with glucose produced a rapid and striking increase of both serum insulin and blood glucose.
A Paradoxical Effect of Chlorpropamide on the Plasma Glucose and Immunoreactive Insulin Response to Intravenous Glucose in Normal Dogs
Authors: Reaven Gerald M , Lindley Thomas S , Weisinger Jose R , Swenson Robert S
Published: December 2014

The effect of various doses of chlorpropamide on plasma glucose and immunoreactive insulin responses to an acute intravenous glucose challenge has been studied in normal dogs. The effects of chlorpropamide were compared to those of placebo in each dog. The administration of 375 mg. of chlorpropamide for four days decreased the ability of the dogs to dispose of a glucose load, and the deterioration in glucose tolerance was accompanied by a marked suppression of the plasma insulin response. Administration of 125 mg. of chlorpropamide for four days led to changes that were qualitatively similar but quantitatively less striking. These results indicate that excessive amounts of chlorpropamide can lead to deterioration in glucose tolerance; this effect seems analogous to induction of glucose intolerance in normal subjects by administration of insulin, as first described by Somogyi. When the chlorpropamide was decreased to a daily dose of 50 mg., dogs were able to dispose of the intravenous glucose load more efficiently than normal. However, this improvement in glucose tolerance was not associated with a significant rise in plasma insulin response. Thus, although it seems reasonable to attribute deterioration in glucose tolerance after excessive doses of chlorpropamide at least partly to inhibition of insulin release, the improvement that occurs after smaller doses does not appear to be due to an absolute increment in the plasma insulin response to glucose.
Effect of Pancreatectomy, with and without Hypophysectomy, and of Insulin Treatment on the Composition of Canine Aorta
Authors: Brosnan Margaret E , Sirek O V , Sirek Anna , Przybylska Krystyna
Published: December 2014

The chemical composition of aorta from normal and endocrine deficient dogs was studied in terms of collagen, elastin, calcium, “water plus lipid” and mucopolysaccharide (MPS) content. The latter component was resolved into four fractions: hyaluronic acid (HA), heparan sulfate (HS), dermatan sulfate (DS), and the isomeric chondroitin sulfates (CS). The results were compared in the following way: (1) normal versus pancreatectomized; (2) hypophysectomized versus hypophysectomized and pancreatectomized (Houssay); and (3) Houssay with and without insulin treatment. Pancreatectomy affected the content of two constituents only: the HS and CS levels were lowered. The low content could be raised by insulin treatment. These results indicate that except for the sulfated MPS, insulin does not appreciably alter the composition of the aortic wall.
Forearm Glucose Uptake During the Oral Glucose Tolerance Test in Normal Subjects
Authors: Jackson R A , Peters N , Advani Usha , Perry Gillian , Rogers J , Brough W H , Pilkington T R E
Published: December 2014

Total forearm glucose utilization (FGU) was determined during 100 gm. oral glucose tolerance tests (GTT) in twenty-five normal volunteers. In addition, the concomitant balance of insulin, growth hormone, and lactate across the forearm was studied in thirteen subjects.

The increment in FGU during the three hours following glucose ingestion amounted to 74 mg./100 ml. forearm; it may be calculated that increased peripheral glucose utilization accounted for the disposal of 42 per cent of the 100 gm. load and that during the GTT some 58 gm. of extra glucose reached the peripheral circulation.

Serum insulin concentrations in mixed venous (MY) blood rose steeply after glucose loading, while growth hormone levels were reduced. Additional observations in thirteen subjects showed that MV insulin levels remained significantly lower than corresponding arterialized venous (AV) concentrations between thirty and 150 minutes, suggesting that insulin was being continually removed bythe forearm tissues during this time. Significant AV-MV differences were not detected in growth hormone levels.

Plasma lactate concentrations rose immediately after glucose loading, reaching a peak at sixty minutes and declining thereafter. The initial elevation was associated with lactate uptake by the forearm and the subsequent fall with lactate release, suggesting that peripheral lactate metabolism has little or no influence on the shape of the lactate response curve. It is suggested thatthis early rise in lactate concentrations is the result of increased hepatic lactate production and that the timing and height of the lactate peak reflect the pattern of enhanced hepatic glucoseutilization after oral glucose loading.

Our results suggest that the disposition of a 100 gm. oral glucose load is accounted for mainly by hepatic glucose conservation rather than peripheral uptake and, therefore, that the former is the major determinant of the shape of the oral glucose tolerance curve.