bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiologic Effects of Metabolic Fuels on Carbohydrate Metabolism: I. Acute Effect of Elevation of Plasma Free Fatty Acids on Hepatic Glucose Output, Peripheral Glucose Utilization, Serum Insulin, and Plasma Glucagon Levels
Authors: Seyffert Willis A , Madison Leonard L
Published: December 2014

The in vivo effects of acute changes in the concentration of plasma free fatty acids on hepatic glucose output and peripheral glucose utilization were defined in thirteen studies in dogs. Dogs with chronic end-to-side portacaval shunts . were used thereby permitting not only measurement of hepatic rather than splanchnic glucose output but also the rate of peripheral glucose utilization. In eighteen additional studies the effect of acute elevations of plasma free fatty acids on serum insulin, plasma glucagon, blood ketones and alpha-amino nitrogen was determined. The quantitative and qualitative changes in plasma free fatty acids which occur during starvation were simulated by the intravenous administration of a cottonseed oil emulsion plus heparin. The acute elevation of plasma free fatty acids produced a 37 per cent decrease in hepatic glucose output and a 30 per cent inhibition of peripheral glucose utilization. This decrease in hepatic glucose output was the consequence both of a significant increase in the secretion of insulin and a decrease in glucagon secretion. These changes in hormonal milieu which attended the increase in plasma free fatty acids could not be ascribed to changes in blood ketones or amino acids since the concentrations of these substances remained unchanged. These data suggest that this feedback of free fatty acids on secretion of insulin and glucagon plays an important physiologic role during starvation in the safe transition from carbohydrate to fat metabolism without the danger of progressive ketoacidosis. it is likely that during starvation plasma free fatty acids contribute to the control and maintenance of a low but vital concentration of plasma insulin.
Effects of Different Levels of Glucose upon the Development of Granulated Beta Cells in Cultures of Pancreatic Primordia from Normal Rat Embryos
Authors: Wells Lemen J , Schweisthal Michael R , Marx Ruth Nunamaker , McKay Marguerite , Saccoman Frank M , Lazarow Arnold
Published: December 2014

Pancreatic primordia from normal rat embryos of 14.5 to 15.5 days postcoitum were grown in organ culture on liquid media with 173, 350, 526 and 995 nig. of glucose per 100 ml. The periods of culture were as follows: eight days (14.5 day embryos) and six days (15.5 day embryos). In cultures grown on the standard medium with 173 mg. of glucose per 100 nil., the pancreatic islets had many granulated beta cells. In cultures grown on high-glucose media with 350, 526 and 995 mg. of glucose per 100 nil. the islets had fewer granulated beta cells.

These observations are interpreted to mean that highglucose levels in the media inhibit the production of granulated beta cells in the islets of the cultures.
Diabetes Prevalence and Serum Uric Acid: Observations among 10,000 Men in a Survey of Ischemic Heart Disease in Israel
Authors: Herman J B , Mount F W , Medalie J H , Groen J J , Dublin T D , Neufeld N H , Riss E
Published: December 2014

In 1963 a long-term incidence study of ischemic heart disease and hypertension was initiated in Israel. A total of 10,059 Jewish men over forty years of age in government service were surveyed. The initial examination included a medical history and determinations of blood sugar, cholesterol,and uric acid. There were 682 men designated as diabetic suspects, because of either a history of diabetes or a casual blood sugar value of at least 130 mg. or both.

Results of previous glucose tolerance tests, fasting blood sugar estimates, and information about treatment were obtained from physicians and clinics, or a glucose tolerance test was done at the survey laboratory. For forty-three men not enough information was obtained to decide whether they actually had diabetes. Seventy-nine men were not diabetic, and sixty-two others were not diabetic but had abnormal glucose tolerance tests. The remaining 498 men were classified as diabetic, and of these 296 had a history of the disease and 202 were newly discovered in the survey.

The prevalence of diabetes was directly related to age. When rates were standardized for age, however, men born in the Middle East, North Africa and Israel had 50 per cent more diabetes than the men born in Europe. Also, there was an association between the prevalence of newly discovereddiabetes and body mass. But this was observed in only one group with respect to prevalence of previously diagnosed diabetics (Middle East-North Africa). Similarly, serum cholesterol was found to have a direct relation to prevalence of newly discovered diabetes, but this association was not established with certainty in respect to the prevalence of previously diagnosed diabetes.

A highly significant inverse relation was observed between diabetes and serum uric acid. Serum uric acid values were lower among men with a history of diabetes than those with newly discovered disease. Both groups had values significantly lower than those of the rest of the survey population, however. Men without diabetes but with slightly abnormal glucose tolerance tests had values similar to those of the nondiabetic subjects. It seemed probable that the lower values accompanied rather than preceded the disease. Possible mechanisms causing increased uric acid excretion in diabetes are discucoed.
Evaluation of the Relative Pathogenic Roles of Diabetes and Serum Cholesterol Levels in the Development of Cardiovascular Lesions in Rats
Authors: Wilson Robert B , Martin Julio M , Hartroft W Stanley
Published: December 2014

Previous studies in our laboratory demonstrated that in partially pancreatectomized diabetic rats fed an atherogenic diet containing 5 per cent cholesterol, serum lipid levels rose higher and cardiovascular lesions were more frequent than in nondiabetic rats fed the same diet for three to seven months. This experiment posed the question: Didthe diabetic state per se or the higher levels of cholesterol associated with it account for the greater number of lesions in the diabetic animals?

To answer this question, the experiment was repeated, but this time some of the diabetic rats were fed diets with lower amounts of cholesterol than before in order to keep their serum cholesterol levels within the same range as those of the nondiabetic animals (intact or partially pancreatectomized but normoglyceinic) fed the basal atherogenic diet.

As before, diabetic rats fed the athero genie diet containing 5 per cent cholesterol developed higher levels of serum cholesterol and more lesions than similarly fed nondiabetics. Other serum lipids were also higher in this group, especially triglycerides and free cholesterol.

When serum cholesterol levels in the diabetic animals were not permitted to exceed those in the nondiabetics, the incidence of vascular lesions in the two groups did not differ.

The diabetic state per se in this mode, therefore, seemed to play a pathogenic role in atherogenesis by elevating serum lipid levels. Results would indicate that, under theseconditions, at any given level of serum lipid, the diabetic artery is not more susceptible than a nondiabetic artery to this type of atherogenic stimulus.
Glucose Tolerance and Related Factors in Dogs Fed Diets of Suboptimal Protein Value
Authors: Heard C R C , Turner M R
Published: December 2014

Littermate dogs were fed from weaning on high-protein diets (HP) or on dietswhich were adequate in calories but marginally deficient in protein (LP). The LP animals grew at a slightly retarded rate but showed no other outward abnormality. In the HP animals, intravenous glucose tolerance (K) increased steadily up to twelve months of age (K = 6) and then declined to the adult value (K = 4.7). These changes were accelerated and exaggerated in LP dogs so that, from seven months onwards, the K values for the LP dogs became progressively lower than those of their HP littermates. Although the LP diet was adequate for adult maintenance and other biochemical signs of proteincalorie deficiency were corrected in the adult, glucose tolerance remained impaired (mean K for HP adults = 4.7 and for LP adults = 3.3). In the LP dog decreasing glucose tolerance was associated with increasing resistance to exogenous insulin.

During pregnancy, the HP animals showed an early increase in K followed by a progressive fall. The LP animals showed little change in K during pregnancy, but after lactation both glucose tolerance and sensitivity to insulin increased. Pups born to LP mothers showed signs of congenital malnutrition; they also showed greatly enhanced glucose tolerance in early life. Young dogs, whether fed HP or LP diets, showed rapid impairment of glucosetolerance when acutely infected with toxocara canis. The findings for dogs are compared with those reported in human diabetes mellitus.
Stimulation of Insulin Secretion by Pancreozymin
Authors: Meade Robert C , Kneubuhler Hans A , Schulte William J , Barboriak Joseph J
Published: December 2014

The peripheral injection of pancreozymin in dogs at doses greater than one-eighth dog unit/kg, has been shown to produce an abrupt rise in portal vein plasma insulin. A dose of 0.5 U./kg. proved to be a more potent stimulus of insulin secretion than 0.5 gm./kg. of glucose. A combination of pancreozymin and glucose produced more pronounced hyperinsulinemia than the sum of the two given separately. Repeated injections of pancreozymin appear to have a decreasing stimulatory effect. Pancreozymin produced a decrease in free fatty acids but did not lower plasma glucose.
Serum Immunoreactive Insulin Response During Prolonged Glucose Infusions in Nondiabetic and Diabetic Humans
Authors: Graber Alan L , Wood Francis C , Williams Robert H
Published: December 2014

Prolonged intravenous glucose infusions were employed to study pancreatic islet cell reserve, measured by responses in serum immunoreactive insulin levels. A continuous intravenous glucose load (6 gm./kg./24 hrs.) was administered for five to seven days to four nondiabetic subjects and five maturity-onset diabetic patients. The nondiabetics assimilated all the glucose, but the diabetics developed marked hyperglycemia and glucosuria. Immunoreactive insulin levels were similar in the two groups, and insulin response to eating breakfast daily during the infusions was at least as high in the diabetics as in the nondiabetics. During these infusions, there was no evidence that the diabetic patients differed from the nondiabetic controls by showing progressive decreases in serum immunoreactive insulin responses.
Influence of Age on the Intravenous Tolbutamide Response Test
Authors: Swerdloff Ronald S , Pozefsky Thomas , Tobin Jordan D , Andres Reubin
Published: December 2014

Intravenous tolbutamide response tests were performed on a selected group of 100 community-dwelling volunteer male subjects aged twenty-one to eighty-one years. A deterioration in performance with age was manifest as a progressively lesser fall and later nadir of blood glucose concentration throughout the early adult years and middle age. There was no further decrease in response after the sixth decade of life.

Many investigations of the tolbutamide response test have been reported since the standards of normality for the test were introduced eight years ago. Those studies, in addition to the present report, show that the application of these standards to diverse population groups results in a very high percentage of “abnormal” or “diabetic” responses. We have considered the reasons for the large variation in response to intravenous tolbutamide reported in the literature. It appears that studies which report relatively large responses to tolbutamide are those in which the subject group was (a) composed predominantly of young adults, or (b) preselected on the basis of superior performance on glucose tolerance tests, or both. Data derived from this type of selection procedure provide standards of normality which are not applicable to the general population. We therefore propose a new approach to the interpretation of the results on the tolbutamide test: A set of nomograms is provided which permits the rapid computation of ageadjusted percentile ranking of an individual's response to intravenous tolbutamide.
Effect upon Insulin Secretion of Physiologic Doses of Glucagon Administered via the Portal Vein
Authors: Ketterer Hermann , Eisentraut Anna Marie , Unger Roger H
Published: December 2014

Rapid endoportal injections of glucagon in a dose (1 μg.) which does not elevate thearterial glucagon concentration beyond the physiologic range caused a prompt rise in both mean arterial glucose and pancreaticoduodenal insulin concentration to a peak six minutes later. Hyperglycemia of similar magnitude produced by intravenous glucose infusion failed to elicit, as great a rise in insulin release.

With smaller doses of glucagon a more variable response was observed; however, in some dogs doses of glucagon which were too small to cause a significant change in arterial glucagon concentration did cause a rise in both glucose and insulin levels.

It is concluded that glucagon administered in physiologic doses via-the portarvenous system elicits a greater rise in insulin release than can be attributed to the concomitant hyperglycemia and, as suggested by others, does possess the qualifications of a potentiator of insulin secretion.
Infants of Diabetic Mothers
Authors: Joassin Guy , Parker Mary L , Pildes Rosita S , Cornblath Marvin
Published: December 2014

Of six infants of gestational diabetic mothers (IGDM), the levels of insulinwere high in four during the first week of life; levels of free fatty acid and glucose tended to be low. Growth hormone values were within normal limits.

In six infants of overt diabetic mothers, five had significant hypoglycemia; three were symptomatic. Growth hormone levels were within normal limits.

There was a positive correlation between the mother's blood glucose and the infant's insulin level at delivery in five of the IGDM. After birth, a negative correlation was found between the infant's blood glucose and the plasma insulin. There was apositive correlation between weight and insulin levels at birth in twenty normal infants and five growth hormone levels and birth weight 1967.
Studies in Stress Glycosuria: II. Glycosuria and Blood Sugar Elevation in Alloxanized Subdiabetic White Rats Subjected to Electric Shock Stress
Authors: Ehrentheil Otto F , Reyna Leo J , Adams Constance J , Giovanniello Thomas J , Chen Edith T
Published: December 2014

White rats made subdiabetic by the administration of small doses of alloxan were stressed by a buzzer and electric shock program for one and one-half hours every week day for four months. An increase in blood sugar with frequent glycosuria was observed immediately after the stress periods. Nonstressed subdiabetic control rats showed glycosuria only rarely. The average fasting blood sugar was 79.25 mg. before stress and 127.87 mg. per 100 ml. after stress, an average increase of 48.6 mg. per 100 ml. above the preshock level. This increase was more than twice as great as that found in normal (nonalloxanized) rats after similar stress. The diabetic indices, calculated from glucose tolerance data, however, were not increased by the stress regimen; they actually decreased, becoming for the most part normal during the months of stress. After termination of stress the diabetic indices of the experimental animals again increased to subdiabetic levels and were then similar to those of the nonstressed alloxanized controls.
Studies on Experimental Insulin Immunity: II. The Organ Distribution of Insulin in Immune Rabbits
Authors: Horino Masaharu , Yu Shiu Yeh , Blumenthal Herman T
Published: December 2014

The circulating half-life of injected insulin-I-125, and the uptake of this radioactive hormone by various tissues, have been compared in the normal and insulin-immune rabbit. In the normal animal the injected radioactive insulin is carried by albumin or an alpha-globulin, while in the immune animal it is carried in complex with antibody. The circulating half-life appears to have a fast and a slow component. In the normal rabbit the fast component was about 4.8 minutes and the slow component about forty-eight minutes, while in the immune animal the former was ten minutes and the latter about ninety minutes.

In the normal rabbit only about 17 per cent of the injected radioactive insulin remained as TCA-precipitable radioactivity (intact insulin) in blood and tissues one hour after injection, while in the immune animal about 75 per cent remained in this form at the end of one hour. It would appear, however, that some biologic effect was derived from the injection of radioactive insulin into immune animals, since some hypoglycemia occurred.

In both normal and immune animals most of the TCAprecipitable radioactivity one hour after injection of radioactive insulin was retained in serum, muscle, kidney and liver. However, the proportion of intact insulin was seventeen times greater in serum, 50 per cent greater in the heart, about 30 per cent greater in liver and muscle, about 16 per cent greater in lung and about the same in kidney of immune as compared with normal rabbits.
Fat Absorption in Diabetes Mellitus
Authors: Corsini G , Gandolfi E , Bonechi I , Cerri B
Published: December 2014

In a group of fifty-eight diabetics (fifty with a family history of diabetes mellitus) in whom the disease was present for at least nine years and in whoin a high prevalence of systemic complications was found, five had steatorrhea. In one of them, the steatorrhea appeared to Be due at least in part, to an-impairment of exocrine pancreatic function. In the others it seemed to be of intestinal origin, although the dotylose test was normal and ieiunal mucosa biopsy did riOt snow significant abnormality. Fecal fat output was measured while the diabetes was rendered poorly controlled, and in two cases the steatorrhea was responsive to improved diabetic control. As far as fat absorption is concerned, no difference was noticed between patients with maturity-onset diabetes and those with diabetes which developed before thirty-five years of age. On the basis of the authors experience and a review of the literature the existence of true diabetic steatorrhea and its diagnosis are discussed.
Factors Determining the Plasma Insulin Response to Oral Glucose in Diabetes Mellitus
Authors: Buchanan K D , McKiddie M T
Published: December 2014

Oral glucose tolerance tests were performed and plasma insulin levels measured by immunoassay in sixty-four diabetic patients. Of the sixty-four, twenty-seven had mild or moderate and thirty-seven had severe carbohydrate intolerance. Of those with moderate diabetes, eleven (41 percent) showed a normal degree of insulin rise, but in eight this was delayed or prolonged. Seven patients (26 per cent) had an excessive insulin response, seven a flat response, and two a low rise with a delayed peak. Of the thirty-seven patients with severe diabetes, thirteen (35 per cent) had a normal degree of insulin rise, although this was prolonged or delayed in six. Only three patients (8 per cent) had an excessive response. Fourteen (38 per cent) had a flat response and seven (19 per cent) a low, delayed rise. Of ten ketotic patients studied, nine had a flat insulin response. Patients whose diabetes had been controlled either on diet or oral therapy, or on both, showed normal or excessive plasma insulin levels after oral glucose. Overweight subjects had higher plasma insulin levels than underweight subjects, but there was no correlation between the insulin levels and the degree of obesity. Mild carbohydrate intolerance was associated with a higher plasma insulin response than was severe carbohydrate intolerance.
Influence of Anti-insulin Serum on Glucose Metabolism: II. In the Perfused Heart
Authors: Mansford K R L
Published: December 2014

1. An improved method of preparing anti-insulin guinea pig serum of high potency is described.

2. Glucose metabolism has been studied in the perfused hearts of rats pretreated with anti-insulin serum. In perfused hearts taken from rats one hour after the injection of 0.5 ml. of anti-insulin serum there was a significant decrease in total glucose uptake, in glucose oxidation and in the lactate and glycogen formation from glucose as compared with values obtained in perfused hearts from normal rats.

3. When insulin was added to the perfusion fluid no significant differences were observed in glucose metabolism in perfused hearts from anti-insulin treated rats and from normal rats.
Influence of Growth Hormone on Insulin Secretion: Studies of Growth-Hormone Deficient Subjects
Authors: Merimee T J , Burgess J A , Rabinowitz D
Published: December 2014

Previous studies in normal females and in stilbestrolpretreated males have revealed increases in plasma insulin and growth hormone (HGH), after infusion of arginine monochloride, and a sharp decrease in free fatty acids (FFA), which return toward normal over two to two and one-half hours. In the present study, similar measurements were made after arginine infusion in subjects who were deficient only in HGH. The rise in plasma insulin levels in the HGH-deficient subjects was less than half the normal response. The fall in plasma FFA levels was similar in normal and in HGH-deficient subjects, but the HGHdeficient group failed to restore their FFA levels to control values over the time of the experiment.
Effect of Chlorpropamide on Serum Glucose and Immunoreactive Insulin Concentrations in Patients with Maturity-onset Diabetes Mellitus
Authors: Reaven Gerald , Dray Jan
Published: December 2014

Serum glucose and immunoreactive insulin responses to an oral glucose load were measured before and several weeks after treatment with chlorpropamide in eighteen patients with maturity-onset diabetes mellitus. The fall in serum glucose concentration produced by the sufonylurea compound was not associated with an increase in serum insulin concentration. Instead, there appeared to be a direct relationship between control of hyperglycemia and associated decreases in insulin concentration. These observations raise the possibility that sulfonylurea compounds may lower glucose concentration by means other than simply stimulating pancreatic insulin secretion.
Clearance and Metabolic Action of Insulin and Nonsuppressible Insulin-like Activity (NSILA) in the Isolated Perfused Rat Heart
Authors: Solomon Solomon S , Challoner David R , Ensinck John W , Williams Robert H
Published: December 2014

Several aspects of glucose-U-C-14 metabolism were studied in the isolated perfused rat heart to compare the activities of nonsuppressible insulin-like activity (NSILA) and crystalline insulin. Like insulin, porcine NSILA prepared on a Dowex-50 column caused significant glucose disappearance and glycogen deposition. While 50 per cent of the insulin was cleared from the perfusate (immunoassay and bioassay) over sixty minutes, NSILA concentration, measured by the isolated fat cell bioassay, remained constant.

These results establish myocardium as a tissue on which NSILA has an action similar to insulin. Furthermore, these studies show an action of NSILA via a “normal” vascular tree and support the possibility that it may have a physiologic role. The lack of clearance of NSILA suggests that it may exert its insulin-like action over long intervals.
Effect of Pancreatectomy on Glucose Tolerance and Extracellular Fluid Insulin in the Dog
Authors: Rasio E A , Hill G J , Soeldner J S , Herrera M G
Published: December 2014

An intravenous glucose tolerance test (IVGTT No. 1) was performed in anesthetized dogs after dissection of the pancreas but prior to its removal. The test was repeated forty minutes (IVGTT No. 2) and three hours and forty minutes (IVGTT No. 3) after the pancreatectomy was completed. Glucose, immunoreactive insulin (IRI), and insulin-like activity (ILA) were measured in serum and in thoracic duct lymph.

During IVGTT No. 1, serum IRI concentration rose sharply and then decreased while lymph IRI increased more slowly and reached a plateau at twice the fasting level. Net glucose disappearance rate (K) was 1.7 per cent per minute.

Forty minutes after pancreatectomy, at the initiation of IVGTT No. 2, lymph IRI had decreased to 50 per cent of the fasting level, but blood glucose concentrations were still within the normal range. At this point, following glucose injection, no increase in serum or lymph IRI was observed and glucose tolerance was subnormal: K = 0.5 per cent per minute.

Further lowering of lymph IRI and hyperglycemia were noted three hours and forty minutes after pancreatectomy. IVGTT No. 3 showed further deterioration of carbohydrate tolerance: K < 0.5 per cent per minute. Thus, progressive reduction in the rate of glucose assimilation was observed pari passu with reduction in the plateau level of interstitial IRI. It is suggested that this moiety is probably the major determinant of net glucose disappearance rate.

Endogenous serum IRI rapidly equilibrated with interstitial fluid IRI. On the other hand, changes in serum “nonsuppressible” insulin-like activity (NSILA) were not reflected in lymph NSILA levels, thus suggesting that this moiety does not play a major role in the assimilation of a glucose load.
Influence of Cortisol on Plasma Insulin in the Sheep
Authors: Bassett J M , Wallace A L C
Published: December 2014

Daily injection of a group of sheep with 75 mg. cortisol acetate (1.2 mg. per kilogram body weight) resulted in hyperglycemia and in a marked increase in plasma immunoreactive insulin concentrations. Doubling the dose of cortisol after fourteen days did not result in further increases in glucose or insulin concentrations, but the elevated levels were maintained throughout treatment. Intravenous glucose tolerance tests using 0.1 gm. glucose per kilogram body weight showed that the rate of glucose removal was decreased and the increment in plasma insulin concentration reduced by cortisol treatment. With a larger glucose load (0.5 gm. per kilogram body weight) there was an exaggerated insulin response to the increased plasma glucose level during the first period of cortisol treatment, but in the second period the response was no greater than that in the control period. Changes in plasma glucose and insulin concentrations in the eight hours following feeding were much exaggerated during cortisol treatment, even though there is little absorption of glucose from the digestive tract in this species.

In the absence of evidence of increased glucose turnover in the sheep during cortisol-induced hyperglycemia, the changes are indicative of marked impairment of peripheral glucose metabolism and antagonism of insulin action by cortisol in this species.
Manifestation of Diabetic Microangiopathy in Nailfold Capillaries
Authors: Terry Erwin N , Messina Edward J , Schwartz M Stephen , Redisch Walter , Steele J Murray
Published: December 2014

An unusual morphologic capillaroscopic finding, named “nodular apical elongation,” is described. It was observed in both, diabetic and nondiabetic subjects, with a significantly higher occurrence in the diabetic patients. Reasons for considering this a part of generalized diabetic microangiopathy are discussed.
Exaggerated Insulin Response to Glucagon in Simple Obesity
Authors: Benedetti Andrea , Simpson Ronald G , Grodsky Gerold M , Forsham Peter H
Published: December 2014

Serum insulin response to intravenous administration of 1 mg. glucagon and 25 or 40 gm. glucose plus 1 mg. glucagon has been studied in normal and markedly obese nondiabetic patients and compared to the responses of infusions of glucose alone.

In both groups, serum immunoreactive insulin (IRI) rose to a maximal level within five minutes after the end of each injection, but the rise was significantly higher in the obese subjects. In spite of the augmented rise of IRI after a glucose plus glucagon infusion, the mean rate of glucose disappearance did not change significantly in the obese subjects, a finding which suggested impaired sensitivity to endogenous insulin. In obese subjects, who are known to have hyperplasia of the islets of Langerhans, the enhancement of insulin secretion by glucagon appears greater.
Failure of Guinea Pig Antibody to Beef Insulin to Neutralize Coypu (Nutria) Insulin
Authors: Davidson J K , Zeigle Marcia , Haist R E
Published: December 2014

Guinea pig insulin is the only mammalian insulin previously known to be nonneutralizable by antibody to beef insulin (Canad. J. Physiol. Pharm. 43:373, 1965). A second nonneutralizable mammalian insulin, that of the coypu (nutria, or myocastor coypus), has been identified. Coypu pancreas yielded 1.95 U. extractable insulin per gram. An amount of guinea pig antibody to beef insulin sufficient to neutralize twenty-five times as much beef insulin had no effect on the increase in glycogen content produced by pancreatic or serum coypu insulin in the mouse hemidiaphragm in vitro. Both 50 mU. coypu insulin alone and 50 mU. coypu insulin plus 150 mU. antibody to beef insulin when injected into mice produced as many convulsions and lowered the blood glucose to the same mean level as did 50 mU. beef insulin alone (12 mg./100 ml.). Mice injected with 50 mU. beef insulin plus 150 mU. antibody did not convulse and had a mean blood glucose of 108 mg./100 ml. Coypu pancreatic extract cross-reacted with guinea pig antiserum to beef insulin in the passive cutaneous anaphylaxsis test.
Effect of Acute Insulin Deprivation on Rat Liver Glucokinase
Authors: Ruderman Neil B , Lauris Vilma
Published: December 2014

The effect of acute insulin deprivation on hepatic glucokinase was studied in the intact rat. Liver glucokinase decreased by 30 per cent within 3 hrs. after the intravenous administration of anti-insulin serum (AIS) to fed rats. Hexokinase activity did not change significantly whereas glucose-6-phosphatase activity rose. The administration of glucagon or puromycin failed to decrease glucokinase activity within 3 hrs. despite the fact that the latter agent depressed leucine incorporation into liver protein by 80 per cent. Subcutaneous administration of nicotinic acid significantly reduced the AIS induced fall in glucokinase. In addition, it completely prevented the rise in serum free fatty acids and also diminished the rise in blood glucose. These findings suggest that in acute insulin deprivation the immediate fall in glucokinase activity results from an accelerated rate of enzyme inactivation rather than an inhibition of enzyme synthesis.
Absorption of Insulin from the Human Small Intestine
Authors: Crane C W , Luntz George R W N
Published: December 2014

Insulin absorption from the human intestine without the necessity of suppressing the activity of pancreatic enzymes has been demonstrated in an adult male subject who survived total pancreatectomy. Following a large dose of insulin the fraction absorbed was small and the reason for this is discussed.
Early Phase of Insulin Release
Authors: Simpson Ronald G , Benedetti Andrea , Grodsky Gerold M , Karam John H , Forsham Peter H
Published: December 2014

The early phase of insulin release in the first five minutes after intravenous administration of glucose, glucagon, and glucose-plus-glucagon was investigated systematically in various clinical conditions.

In normal subjects there is an immediate release of insulin after glucose, glucagon, and glucose-plus-glucagon infusions. The latter combination produced the highest insulin levels.

Of a group of nonobese subjects with diabetic heritage, some had impaired early release of insulin, but0 their mean response did not differ significantly from the normal group.

Investigation of nonobese potential diabetics (offspring of two diabetic parents) revealed that as a group average they had decreased insulin levels during the early phase of insulin release, even though intravenous glucose tolerance was normal. Four of ten subjects had a normal response.

Nonobese, noninsulin-dependent diabetics had no insulin response to infused glucose, but when glucagon was added to glucose a significant and rapid insulin discharge was observed. However, the magnitude of this response was about half that seen in normal subjects after glucose-plusglucagon.

Finally, the early phase of insulin release was studied in obese nondiabetic subjects who demonstrated an exaggerated insulin release to each stimulus. Again, glucose-plusglucagon was the most potent stimulator of insulin release.

It is postulated that impairment in the early phase of insulin release may be the first detectable abnormality of insulin secretion in diabetes mellitus and that glucagon has the capability of restoring this toward normal.
Diabetes Mellitus in Twins
Authors: Gottlieb Marise S , Root Howard F
Published: December 2014

Among 242 sets of twins collected from 34,072 Joslin Clinic records from 1949 to 1966, there were 104 sets with both members alive. Of these, forty-seven sets were examined and an additional forty-three sets responded to a detailed questionnaire. A high concordance for overt diabetes was found in monozygotic sets in which the proband was age forty or greater at time of diagnosis. In the forty-seven sets examined, there were no cases of overt diabetes in the dizygotic twin siblings of a proband who was age forty and over at time of diagnosis of overt diabetes. Surprisingly, however, a high rate of chemical diabetes was diagnosed in the dizygotic twin siblings, an observation implying an etiology for diabetes mellitus more complex than inheritance by a single recessive gene.
Isolation and Properties of Proinsulin, Intermediate Forms, and Other Minor Components from Crystalline Bovine Insulin
Authors: Steiner Donald F , Hallund Ole , Rubenstein Arthur , Cho Sooja , Bayliss Claudia
Published: December 2014

Methods are described for the isolation in nearly pure form of bovine proinsulin, a single polypeptide chain precursor of insulin, and of intermediate forms of proinsulin having two polypeptide chains. The intermediate forms represent proinsulin molecules in which one or more cleavages have occurred at the site of attachment of the connecting peptide (C-peptide) to the A chain. A third fraction is apparently unrelated to proinsulin but appears instead to be an aggregate of insulin (possibly a covalent dimer) which behaves similarly to proinsulin during gel filtration. The purified fractions all react with antisera to insulin and all have been shown to have measurable biological activity. The purified intact proinsulin has very low biological activity, but can be converted to fully active deatanated insulin upon incubation with trypsin. The possible relevance of proinsulin to a fuller understanding of the β cell derangements in human diabetes is briefly discussed.
Effects of Tolbutamide and Insulin on Insulin Inhibitory Activity Associated with Plasma Albumin
Authors: Devrim Sevim , Kilo Charles , Voyles Nancy , Recant Lillian
Published: December 2014

A reproducible pattern of change in insulin inhibitory activity associated with plasma albumin has been demonstrated. In six normal subjects, intravenous Na tolbutamide increased inhibitor activity to levels seen in many diabetics. Similar increases were seen in certain diabetic patients but not in all. Intravenous exogenous insulin also increased inhibitory activity. Since the latter could be demonstrated in the absence of hypoglycemia, the increase in inhibitor was probably related to the increase in insulin molecules. The time of inhibitor appearance suggests that it may be a product of insulin metabolism but other possibilities exist.
Adsorption of Insulin to Infusion Bottles and Tubing
Authors: Weisenfeld Shirley , Podolsky Stephen , Goldsmith Lowell , Ziff Lawrence
Published: December 2014

The adsorption of clinically used quantities of insulin to infusion systems was studied. Isotonic saline solutions containing tracer quantities of beef insulin-I-131, with or without varying amounts of nonradioiodinated (carrier) regular beef insulin, were added to bottles of 500 ml. infusion sets. The solutions were then allowed to flow out into collection beakers. Adsorption was assessed by measuring the decrease of radioactivity in the solutions and/or recovery from the bottles by 30 per cent potassium hydroxide (KOH). The influence of human serum albumin (HSA) on adsorption was evaluated by repeating the experiments after HSA was added to the infusion fluid.

Adsorption of insulin-I-131 to both bottles and tubing was considerable, especially at low concentrations of carrier insulin. HSA effectively reduced the adsorption to clinically insignificant amounts.
Secretory Granule Formation and Release in Rabbit Pancreatic A-Cells
Authors: Lazarus Sydney S , Shapiro Stanley , Volk Bruno W
Published: December 2014

A-cells of the islets of Langerhans from normal rabbits as well as rabbits treated with insulin, cortisone, or tolbutamide or subjected to a semistarvation diet were studied by light and electron microscopy. Consistent morphological differences between A-cells of normal and experimentally treated rabbits were not found. Individual A-cells varied considerably in degree of granulation and cytoplasmic electron density, however it was not possible to distinguish between A1- and A2-cells. Evidence is presented demonstrating that A-cell granules are formed in the Golgi complex, migrate to the cell membrane, and are extruded intact to the capillary border of the cell between the plasma membrane and basement membrane. The A-cell granules then appear to undergo dissolution and resorption. Based on the morphologic findings no relationship of glucagon secretion to insulin release could be established.
Inhibition of Fatty Acid Stimulation of Gluconeogenesis by (+)-Decanoylcarnitine in Perfused Rat Liver
Authors: Williamson John R , Browning Edward T , Scholz Roland , Kreisberg Robert A , Fritz Irving B
Published: December 2014

Oleic acid produced a two- to three-fold stimulation of glucose production from lactate in perfused livers from fasted rats. This effect was completely blocked by (+)-decanoylcarnitine, a known inhibitor of (−)-carnitine palmityltransferase. Activation of fatty acids to the acyl CoA esters was not inhibited. Neither β-oxidation of octanoate, nor its stimulatory effect on gluconeogenesis was blocked by (+)-decanoylcarnitine. The results show that in the intact liver, the oxidation of long-chain but not short-chain fatty acids proceeds almost entirely through carnitine-dependent pathways.

Changes in the tissue levels of metabolic intermediates after addition of oleic acid show that the increased rate of gluconeogenesis was caused by a stimulation of the pyruvate carboxylase step. Attendant increases in the levels of acetyl CoA and NADH are consistent with the proposal that the mitochondrial levels of these intermediates control carbohydrate metabolism by diverting pyruvate from oxidation towards the synthesis of glucose. A further control site was identified upon fatty acid addition in the region of the phosphofructokinase and fructose diphosphatase reactions. There was no evidence for control at either of these steps by adenine nucleotides, but a marked rise of citrate was consistent with a postulated inhibition of phosphofructokinase. All the changes in the levels of intermediates of the gluconeogenic pathway and citric acid cycle induced by oleic acid were blocked by (+)-decanoylcarnitine. The failure of oleic acid to increase acetyl CoA and citrate levels in the presence of (+)-decanoylcarnitine explains its failure to stimulate gluconeogenesis under these conditions. It is concluded that the effect of fatty acids on gluconeogenesis is determined by their rate of oxidation and not by their concentration in the perfusion fluid.

The significance of these findings in relation to the interactions of carbohydrate and fatty acid metabolism in vivo in the normal, starved and diabetic states is discussed.
Analysis of Tests for Diabetes in 250,000 Persons Screened for Diabetes Using Finger Blood after a Carbohydrate Load
Authors: Kent Gerald T , Leonards Jack R
Published: December 2014

The results of a detection program for diabetes over a four-year period, using a finger blood test after a carbohydrate load, were analyzed. After excluding persons with known diabetes or incomplete data, 250,938 had the initial screening test and 9,682 or 3.9 per cent screened “positive.” Approximately 75 per cent of the “positive” screenees returned for a confirmatory carbohydrate tolerance test. Five thousand, three hundred and seventy persons, or approximately 74 per cent of those who returned, had “positive” confirmatory tests. Since only persons who were “positive” in both tests were considered to have diabetes, the prevalence rate for previously undetected diabetes was 2.1 per cent.

When allowance was made for “positive” screenees who failed to return by assuming that they would confirm “positive” at the same rate as the returnees, the estimated prevalence rate for previously undetected diabetes was 2.8 per cent.

A representative sample of 100,077 persons showed very similar test results which were further analyzed by sex, race, weight and family history in relation to decades of age. The prevalence rate of undetected diabetes and the rate of “positive” confirmation for “positive” screenees varied markedly with age. The importance of considering the other variables in relation to age for planning detection programs is discussed; 60 per cent of the persons with diabetes detected in this program had a negative family history for diabetes.

Information from return postcards sent to “positive” screenees from three months to three years after their initial test showed that a very high percentage of screenees had consulted their physicians as a result of the test; 62 per cent of the confirmed “positives” who replied stated that the diagnosis of diabetes had been confirmed by their physicians.
Failure to Demonstrate “Bound” Insulin in Human Serum
Authors: Meade Robert C , Brush James S , Klitgaard Howard M , Ward Walter F , Ratz Margaret
Published: December 2014

The reported insulin-like activity, ILA, eluted from a cation resin column, following passage of serum, has been confirmed using the rat diaphragm bioassay. Four methods reported to convert “bound” to “free ” insulin did not increase assayable ILA.

A quantitative estimate of ILA in the untreated preparation using the rat diaphragm assay was greater than the estimate obtained using the mouse in vivo assay. It is concluded that rat diaphragm measures total ILA without prior activation. These studies fail to support the concept of “free” and “bound” insulin in human serum.
Glucose-Fatty Acid Interactions in the Rat Diaphragm in Vivo
Authors: Schonfeld Gustav , Kipnis David M
Published: December 2014

The functional significance of the plasma free fatty acid (FFA) level as the causal mediator of glucose-fatty acid interactions in striated muscle has been examined in the diaphragm of the intact rat. Acute elevations of the plasma FFA by the fat meal-heparin regimen or the intravenous injection of anti-insulin serum did not result in the intracellular accumulation of free glucose in the rat diaphragm even when glucose transport rates were markedly accelerated by the concomitant administration of a glucose load and insulin, thereby indicating that phosphorylation in this tissue was not significantly depressed by high plasma FFA levels. The tissue FFA level was shown to vary independently of the plasma FFA level (e.g., prolonged starvation, following insulin administration to the seventy-two hour alloxan diabetic rat). The suggestion is made that the tissue fatty acid moiety rather than the plasma FFA level is the major determinant in glucose-fatty acid interactions in striated muscle.
Insulin Disposition in the Isolated Perfused Rat Heart: Effect of “Bound” Insulin
Authors: Posner Barry I , Sotman Stuart L , Antoniades Harry N
Published: December 2014

Hearts from fed and fasted rats were perfused with modified Krebs-Ringer bicarbonate buffer containing 3 per cent human serum albumin, 2 mg./ml. glucose and 100 or 200 μU./ml. crystalline insulin. The concentration of immunoassayable insulin in the medium decreased, during two hours of perfusion, to approximately 50 per cent of the initial concentration. Perfusion of hearts with insulin-I-131 (100 μU./ml.) resulted in: (1) a decrease in immunoprecipitable radioactivity corresponding in rate and extent to that of crystalline insulin; (2) a significantly smaller decrease in trichloracetic acid (TCA)-precipitable radioactivity; (3) a corresponding accumulation of a fraction of radioactivity which was TCA-precipitable but not immunoprecipitable (TCA-nonimmunoprecipitable) as well as an increase in TCA-soluble radioactivity. Immunoprecipitable-I-131 and not TCA-precipitable I-131 more accurately reflects the fate of intact insulin. Analysis of the two-hour perfusate by gel nitration chromatography (Sephadex G-100) indicated that radioactivity was associated with both the insulin-I-131 peak (M.W. 12,000) and with substances exhibiting a lower molecular weight. Thus, the disappearance of insulin during heart perfusion may be largely accounted for by degradation of insulin.

Both immunoassayable insulin and immunoprecipitable insulin-I-131 were demonstrated to decrease in concentration in cell-free medium which had been previously perfused through the heart for two hours, but not in unperfused medium. The extent of disappearance was less than that during a two-hour heart perfusion. Thus, a portion of the degradation of insulin occurring during heart perfusion is probably due to the action of enzymes which diffuse into the medium from the heart.

“Bound” insulin inhibited the disappearance of both crystalline insulin and immunoprecipitable I-131 radioactivity from the medium during heart perfusion. “Bound” insulin was shown to inhibit the rate of disappearance of immunoprecipitable radioactivity from preperfused medium. During perfusions with “Bound” insulin alone, the level of bioassayable activity in the medium remained constant throughout the perfusion, indicating a lack of disappearance of “Bound” insulin from the medium and vascular space of the heart. Studies of glucose uptake during heart perfusion demonstrated that “Bound” insulin has minimal or no effect on basal and insulin-stimulated glucose uptake. “Bound” insulin may inhibit the disappearance of insulin by interfering with the transport of insulin across the capillary wall and/or by inhibiting the degradation of insulin in the medium.
Studies of a Simplified Plasma Insulin Immunoassay Using Cellulose Powder
Authors: Zaharko Daniel S , Beck Lyle V
Published: December 2014

A modified plasma radioimmunoassay has been developed that uses a cellulose slurry to separate bound from free insulin. This material, which is commercially available, shelf stable, and simple to prepare, makes it possible to run the entire method in test tubes and to use a low specific activity insulin. Details concerning conditions and materials that determined sensitivity, accuracy, and precision are reported. The method is sensitive to about 10 μU/ml. of plasma and has a reproducibility of approximately ± 15 per cent. This method is proposed for use by those who desire to measure rises in plasma insulin by a simple, rapid and reasonably accurate technic.
A Three-Year Trial of Atromid Therapy in Exudative Diabetic Retinopathy
Authors: Duncan L J P , Cullen J F , Ireland J T , Nolan J , Clarke B F , Oliver M F
Published: December 2014

A three-year trial of Atromid treatment in exudative diabetic retinopathy was carried out in twenty-three patients and twenty-five controls.

In comparison with those of the controls the eyes of the Atromid-treated patients showed a highly significant decrease in hard waxy exudates (p = < 0.0001) which was not, however, accompanied by appreciable improvement in visual acuity. No improvement in the vascular retinal lesions occurred.

The initial severity of the exudative lesions was not related to the fasting serum cholesterol or triglyceride levels; there was also no correlation between the effect of Atromid on the exudates and on these serum lipids.

The way in which Atromid might influence exudate deposition and its possible use in the treatment of exudative diabetic retinopathy are discussed.