bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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.
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.
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.
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.
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.
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.
A Comparison of Acid Regular and Neutral Regular Insulin: Responses of Normal Fasted Subjects to Varying Doses of Regular Insulin
Authors: Galloway John A , Root Mary A , Rathmacher Robert P , Carmichael Ralph H 
Published: December 2014

Acid Regular insulin (ARI) and neutral Regular insulin (NRI) were compared in normalfasting subjects by means of a Latin-square experimental design. Both blood glucose and serum immunoreactive insulin were measured after the administration of 0.1 and 0.2 U. per kilogram intravenously, and 0.1, 0.2, and 0.3 U. per kilogram subcutaneously. No statistically significant differences were detected between ARI and NRI.
Analysis of blood glucose and serum insulin data pooled from the ARI and NRI treatments disclosed resistance to increasing doses of insulin as the blood glucose fell below 50 to 60 mg. per 100 ml. Thus, relatively small increments in hypoglycemic activity occurred when the intravenous dose was doubled from 0.1 to 0.2 U. per kilogram or the subcutaneous dose increased from 0.2 to 0.3 U. per kilogram in spite of doubling the hypoglycemic effect when the subcutaneous dose was doubled from 0.1 to 0.2 U. per kilogram. In addition, for each 0.1 U. per kilogram of subcutaneouslyadministered insulin the maximum serum levels were approximately 15 to 30 μU. per milliliter andthe duration of effect was extended by one hour. Therefore, following 0.1 U. per kilogram the maximum effect was over by three hours, after 0.2 U. per kilogram by four hours, and 0.3 U. per kilogram by five hours. These results demonstrate the feasibility of studying the time action of insulin in normal subjects and document the conclusion that duration of effect is a function of the dose given.
Influence of Nicotinamide and Pyridine Nucleotides on Streptozotocin and Alloxan Induced Pancreatic B Cell Cytotoxicity
Authors: Lazarus Sydney S , Shapiro Stanley H 
Published: December 2014

Pancreas from mice treated with 500 ing. per kilogram of nicotinamide intraperitoneally fifteen minutes before 200 nig. per kilogram of streptozotocin intravenously showed mostly unaltered islet B cells after eight, eighteen or fortyeight hours. Mice pretreated with 1,500 mg. per kilogram of either NAD, NADP or NADPH intraperitoneally showed almost no B cell lesions at eight hours. At eighteen hours some B cell necrohiosis was observed but of lesser extent than that seen after streptozotocin alone at eight hours. At forty-eight hours B cells showed diffuse, uniform necrobiosis only slightly less extensive than that seen in the group treated with streptozotocin alone.
Pretreatment of mice with 500 mg. per kilogram nicotinamide intraperitoneally fifteen minutes before 100 mg. per kilogram alloxan intravenously failed to alter the extent of islet B cell lesions at eighteen hours. When the dosage of nicotinamide administered was increased to 1,000 mg. per kilogram and the time of pretreatment at this dose level increased to sixty minutes there was a slight decrease in the extent of B cell necrosis. Islets from rats pretreated with 1,000 mg. per kilogram nicotinamide intravenously sixty minutes prior to alloxan also showed a general lack of protective influence. Under the same conditions nicotinamide completely protected rats against the B cell cytotoxicity of streptozotocin.
These findings demonstrate the almost specific protective action of nicotinamide against streptozotocin-induced B cell necrosis. While pyridine nucleotides slowed its development they did not prevent B cell necrosis after streptozotocin. The dissimilarity in the action of nicotinamide and pyridine nucleotides makes doubtful the view that streptozotocin-induced B cell necrosis is mediated via lowering of cellular content of NAD or other pyridine nucleotides below critical levels. The minimal protection afforded by nicotinamide against alloxan-induced B cell necrosis, as contrasted with its effectiveness against streptozotocin, confirms the view that the basic mechanisms of action of these drugs are different despite comparable selective B cell cytotoxicity.