bluuebunny/crossref_metadata_2025 huggingface dataset:
The Reaction of Rabbit Anti-beef Insulin Serum with Heterologous and Homologous Insulin Preparations
Authors: Narahara H T , Williams Robert H
Published: December 2014

A method for assaying antibodies to insulin that is based on the protection of insulin-I-131 from degradation by a liver extract is described. Moderately potent antibodies to insulin were obtained in rabbits by the injection of crystalline beef insulin, and a high degree of insulin resistance was demonstrable in some of the animals. The immunized animals did not become diabetic.

The biological activity of various insulin preparations was detected by their ability to lower the blood sugar of rabbits or through the stimulation of glucose uptake by the rat hemidiaphragm. Crystalline beef insulin and crude extracts of beef pancreas were effectively neutralized under the conditions of the tests whereas corresponding pork insulin preparations were incompletely neutralized in the rat hemidiaphragm assay. The insulin activity of sera from beef, pork, sheep and human sources was neutralized by the rabbit antisera.

The insulin activity of rabbit pancreas extracts and rabbit sera exhibited significant individual differences in the extent of neutralization. These observations on rabbit insulin preparations support the concept of Moloney and Coval that insulin of a given animal species can exist either in a “native” form that is not readily neutralized by antiserum produced in the same species, or an “altered” form that can be neutralized.
Alloxan Diabetes in the Golden Hamster, Mesocricetus Auratus: II. Glomerulosclerosis and Its Relation to Diabetes Regulation
Authors: Beaser Samuel B , Sak Matthew F , Donaldson George W , McLaughlin Robert J , Sommers Sheldon C
Published: December 2014

A diffuse glomerulosclerotic lesion occurs in the kidney of the alloxan-diabetic golden hamster. The lesion was distinguished from changes associated with aging and consisted of alterations in the basement membranes of glomerular capillaries comparable to some diffuse glomerulosclerotic lesions described in the kidneys of diabetic patients. With poor regulation of the diabetes the incidence of advanced glomerulosclerosis was significantly greater.
Retinopathy in a Dog Following Diabetes Induced by Growth Hormone
Authors: Hausler H R , Sibay T M , Campbell James , Lazdins V
Published: December 2014

Retinal microaneurysms and hemorrhages were observed in a metasomatotrophin-diabetic dog that had remained in the diabetic state for a period of ten years. The history of this dog, described in the text, was involved. There is reason to believe that the retinal lesions developed during the final two years.
On the Mechanism of Insulin Hypersensitivity in Adrenocortical Insufficiency
Authors: Wajchenberg Bernardo Léo , Pereira Virgílio Goncalves , Pupo Armando Aguiar , Shnaider José , de Ulhoa Cintra Antonio Barros , Mattar Emilio , Paulo Sāo
Published: December 2014

A study of the sensitivity to a test dose of exogenous insulin was undertaken in eight patients with primary and five with secondary (Sheehan's syndrome) adrenal insufficiency. The great majority showed hypersensitivity to insulin and hypoglycemia-unresponsiveness was present in all.

The hypersensitivity was primarily the result of excessive peripheral insulin action as shown by the increased disappearance rate (k) of an intravenous glucose load, in the well nourished patient.

A possible failure in glycogenesis and consequent reduced glucose release by the liver, which might explain the hypoglycemia-unresponsiveness, was not confirmed by the glucagon test, suggesting that if there is liver impairment it is in its rate of glucose release independent of the amount of glycogen present and related to the glucocorticoid influence on the threshold of blood glucose regulation by the liver.
Separation of Human Insulin, Glucagon and Other Pancreatic Proteins
Authors: Lochner J de V , Esterhuizen A C , Unger R H
Published: December 2014

Purified human insulin and beef-pork glucagon were subjected to electrophoresis on cellulose acetate strips. Insulin was found to migrate rapidly towards the anode as a single band, while glucagon migrated slowly towards the anode in two distinct fractions. Virtually complete separation of the two hormones was achieved.

Electrophoresis of acid alcohol extracts of human pancreas revealed eight positively migrating bands. By means of densitometric, radioisotopic, and radioimmunochemical technics, fraction 2 was identified as the insulin-bearing fraction, and the area of fractions 7 and 8 as the glucagonbearing region. By gel filtration substantial quantities of the unidentified extraneous proteins, which make up the bulk of the pancreatic extract, were removed, thereby providing purer samples for electrophoresis.

The technic makes possible the rapid preparation of relatively pure samples of glucagon-free insulin and insulinfree glucagon from the pancreas of man and other species in quantities sufficient for laboratory studies. In addition, the characterization of the electrophoretic mobility of these hormones provides a new means by which they may be identified in unknown samples.
Blood Ketone Response to Norepinephrine-induced Free Fatty Acid Elevation in Diabetes
Authors: Blackard William G , Omori Yoshiaki
Published: December 2014

1. During ninety-minute norepinephrine infusions, blood free fatty acid and ketone responses of Japanese nondiabetic and diabetic subjects were determined. Nonobese diabetic subjects with and without fasting hyperglycemia demonstrated significantly greater blood ketone elevations than nondiabetics.

2. An inverse correlation between obesity and blood ketone response to norepinephrine was observed in diabetics. This correlation could not be attributed to varying degrees of fasting hyperglycemia or free fatty acid elevation.

3. Nonobese diabetics with mild fasting hyperglycemia (90 to 150 mg. per 100 ml.) exhibited an unexpected greater increase in blood ketones than nonobese diabetics with moderate fasting hyperglycemia (150 to 250 mg. per 100 ml.). Differences in free fatty acid elevations were not responsible for this apparent paradox.

4. The magnitude of the hyperketonemic response, though dependent on free fatty acid elevation, seemed more sensitive to the degree of obesity and the fasting blood glucose level. Fractional ketone body measurements indicated that the blood ketone elevations were predominantly due to fihydroxybutyric acid increases.
The Prednisolone Glucose Tolerance Test in Pregnancy
Authors: Kyle G Clayton , Yalcin Saliha , Drewyer Richard , Carruthers Bruce
Published: December 2014

The response to a prednisolone glucose tolerance test (PGTT) was investigated in 166 pregnant women, divided into control and diabetes-suspect groups. The diabetes-suspect group consisted of pregnant women with a history of a large infant, a family history of diabetes and/or glycosuria during a previous pregnancy. Positive responses by the criteria of Fajans and Conn occurred in 23 per cent of the control group and 44 per cent of the suspect group. After excluding women with abnormal glucose tolerance tests (GTT), the prevalence of positive responses fell to 15 per cent in the control group and 31 per cent in the suspect group. Thirty patients with normal GTT but positive PGTT during pregnancy were studied at varying intervals after delivery. Half of them reverted to normal PGTT. The increased frequency of positive responses to the PGTT in the suspect group suggests that this presumably more rigorous test of islet reserve may permit recognition of suboptimal islet capacity during pregnancy.
Further Studies of an Inhibitor of the Two Antibody Immunoassay System
Authors: Morgan Carl Robert , Sorenson Robert L , Lazarow Arnold
Published: December 2014

Previous studies with the two antibody immunoassay method have demonstrated the presence of an “inhibitor” in fresh plasma which interferes with the precipitating step of the two antibody system.

Immunoelectrophoretic studies described here demonstrated no cross-reactivity of rat or human gamma globulin with anti-guinea pig plasma (rabbit source), which had been suggested by other workers.

Concomitant inactivation of complement and “inhibitor” by heat, antigen-antibody complex, EDTA, or ammonia indicates that complement is the inhibitor of the two antibody immunoassay system.

EDTA (0.01 M) inactivates the plasma “inhibitor,” permitting assay of undiluted plasma by the two antibody method.
Insulin-like Activity of Dilute Human Serum Assayed by an Isolated Adipose Cell Method
Authors: Gliemann Jørgen
Published: December 2014

A method for insulin assay using isolated adipose cells is described. Fat cells incubated in Krebs-Ringer bicarbonate buffer containing glucose (0.1 mg. per ml.) and albumin (5 per cent) converted glucose-l-14-C to Co2. Addition of insulin caused a maximal stimulation of about eight- to sixteen-fold of the Co2 production. The dose-response relationship exhibited a typical sigmoid shaped curve. The minimum detectable insulin concentration was about 2-5 μU. per ml.; the maximum response was obtained with insulin concentrations of about 300 to 600 μU. per ml. In the optimal range (about 20 to 160 μU. per ml.) the insulin concentrations were determined with a precision of about ±10 per cent (four replications).

This method was applied to human serum. It appeared that dilute (1 per cent), dialyzed, fasting serum contained large amounts of “insulin-like” activity (about 20 to 70 μU. per ml.). The dose response relationship of dialyzed serum in a concentration less than about 2 per cent paralleled that of insulin. The increment in Co2 production with greater serum concentrations was less than the increment with greater insulin concentrations. The insulin-like activity of 1 per cent serum did not change after an intravenous glucose load; it was not suppressed by addition of insulin antibodies. Fractionation of serum by starch block electrophoresis located all of the activity in a broad peak in the (β-γ globulin region. Insulin added to serum was quantitatively recovered in a separate peak located in the slower moving component of the albumin fraction. When serum was subjected to gel nitration on Sephadex G 75 the “insulin-like” activity emerged with the total excluded fraction whereas insulin added to serum was retarded on the column. These properties were similar to those of the previously described “atypical” insulin. Its nature remained undefined.
Serum Insulin-like Activity in Hypophysectomized and Depancreatized (Houssay) Dogs
Authors: Schoeffling Karl , Ditschuneit Hans , Petzoldt Rudiger , Beyer Jurgen , Pfeiffer Ernst F , Sirek Anna , Geerling Herbert , Sirek Otakar V
Published: December 2014

Serum insulin-like activity was measured serially by the epididymal fat pad method in twelve dogs over several weeks. The animals were first hypophysectomized and subsequently pancreatectomized; no insulin was administered at any stage of the experiment. Hypophysectomy resulted in a reduction of serum ILA of some 50 per cent from an average normal fasting value of 420 μU. per ml.

Subsequent pancreatectomy caused no further appreciable reduction in serum ILA over the entire observation period of five weeks. In a selected number of serum samples residual ILA was detectable also by the rat hemidiaphragin procedure. None of the Houssay dogs had measurable amounts of insulin in blood by immunoassay. It was considered unlikely that activities measured by the two bio-assays represented insulin.
Importance of the Hematocrit in Interpretation of Blood Sugar
Authors: Dillon Richard S
Published: December 2014

1. The glucose concentration in whole blood may be calculated with reasonable accuracy from the plasma sugar level and the hematocrit by the following formula: WBS = PS (1-0.30 hct.).

2. Anemia must be recognized as a factor contributing to an apparent decreased glucose tolerance seen in chronic diseases.
Studies on Diabetic Retinopathy: II. Retinopathy and Nephropathy in Spontaneous Canine Diabetes
Authors: Patz Arnall , Berkow Joseph W , Maumenee A E , Cox James
Published: December 2014

Retinal and renal observations on dogs with spontaneous diabetes mellitus are presented. Retinal vessels were prepared by the trypsin digestion, flat retinal technic and examined by light microscopy. Kidneys were examined by light and electron microscopy. Nondiabetic dogs of comparable ages served as controls.

Retinal vessels in some diabetic subjects showed mural pericyte degeneration with “ghost” formation and zones of focal acellularity surrounded by aneurysms or hypercellular capillary shunts. These changes were indistinguishable from those observed in human diabetic retinas prepared by the same technic. Kidneys of the diabetic dogs showed a significantly greater incidence and severity of diffuse glomerulosclerosis and thickening of the basement membrane of the peripheral glomerular capillary loops than was found in the controls. Nodular glomerular lesions of Kimmelstiel and Wilson were not observed.

Cataracts were noted in all diabetic animals with diabetes known to be six months in duration or longer but were rare in the controls.

The pancreas was either described grossly by the contributing veterinarian or submitted for histologic examination in eight of the diabetic dogs. Five of these suggested possible pancreatitis and their diabetes may be secondary to pancreatic disease. The remaining three dogs with no evidence of pancreatitis are considered as primary (possibly hereditary) diabetes mellitus. Retinopathy and prominent diffuse glomerulosclerosis occurred in diabetic dogs with and without evidence of pancreatitis.
Effect of Adrenal Steroids on Glucose Kinetics in Normal and Diabetic Dogs
Authors: Ninomiya Rikuo , Forbath Nicholas F , Hetenyi Geza
Published: December 2014

The rates of endogenous glucose production, utilization, the amount of the intermixing glucose (“pool”) and the apparent distribution space were measured in conscious, trained normal and depancreatized dogs by the method of successive measured injections of tracer. During the intravenous infusion of hydrocortisone or methylprednisolone both the rates of glucose production and utilization fell in normal dogs. Since the same effect was obtained during the infusion of hydrocortisone in depancreatized dogs this effect of adrenal steroids does not seem to be due to an extra release of insulin.

In normal dogs, daily injections of 4 mg. per kilogram of methylprednisolone for one week significantly increased the rates of glucose production and utilization and also the amount of intermixing glucose and the apparent glucose space, without any significant change in the concentration of glucose in the blood plasma. Prolongation of methylprednisolone treatment for a second week caused a further increase in all four parameters again with no change in plasma glucose level. The intravenous infusion of glucose was found to diminish the rate of endogenous glucose production to the same degree before as after one week of methylprednisolone treatment. In diabetic dogs deprived of insulin, two daily injections of methylprednisolone increased the rate of glucose production and the plasma concentration but not the apparent distribution space of glucose. These experiments indicate that in dogs the homeostasis of plasma glucose level is maintained in spite of markedly increased gluconeo genesis if pancreatic function is unimpaired.
Effect of Anaerobiosis and Cell Poisons on Glucose Uptake of Hemidiaphragms and Epididymal Fat Pads in Vitro
Authors: Short A L , Wright F E , Whitney J E
Published: December 2014

An attempt has been made to repeat the observations that anaerobiosis, 2:4-DNP, and the sodium salts of cyanide, arsenite, arsenate, and salicylate all stimulate the glucose uptake of hemidiaphragms in vitro in a way that has been postulated to be analogous to the action of insulin. The glucose uptakes of hemidiaphragms and fat pads have been measured in bicarbonate and phosphate buffers. In no case did anaerobiosis stimulate glucose uptake. Anaerobiosis reduced but did not abolish the effect of insulin.

The effects of the cell poisons were diverse and appeared to be related to both the tissue used and the medium employed. The sodium salts of cyanide, arsenite, and arsenate stimulated the glucose uptake of hemidiaphragms in bicarbonate buffer, whereas, only arsenate was effective in phosphate buffer. When fat pads were incubated in bicarbonate buffer, arsenate and cyanide increased glucose uptake; in phosphate buffer only arsenate was effective. In addition, 2:4-DNP markedly inhibited the glucose uptake of hemidiaphragms in both bicarbonate and phosphate buffers but was without effect on the fat pads. Most of the cell poisons reduced or abolished the effect of added insulin.

These results are discussed with relation to the theory that insulin acts to divert energy away from a process that restricts the entry of glucose into the cell under basal conditions.
Etiological Factors in Thiazide-induced or Aggravated Diabetes Mellitus
Authors: Chazan Joseph A , Boshell Buris R
Published: December 2014

Nine patients with diabetes mellitus and three normal controls were treated for one week with hydrochlorothiazide (150 mg. per day), and certain effects on carbohydrate metabolism were observed. Evidence presented in this study confirms the thiazide-induced carbohydrate intolerance. Tests of insulin reserve (serum ILA response to glucose), response to insulin, insulin binding, urinary steroid excretion, serum potassium, serum nonesterified fatty acids, and serum amylase failed to reveal any abnormality related to the carbohydrate intolerance. There was reduction of the whole blood glutathione levels in six of seven subjects. DIABETES 14:132–36, March 1965.
Infants of Diabetic Mothers: Neonatal Problems and Their Management
Authors: Hubbell John P , Drorbaugh James E
Published: December 2014

A study of neonatal problems of 329 liveborn infants of diabetic mothers indicates that prematurity is the single most significant factor influencing outcome. The direct relationship of prematurity to increased incidence of respiratory distress syndrome, hyperbilirubinemia, and neonatal mortality is demonstrated. Severity of maternal diabetes, while extremely important in relation to stillbirth, does not seem to be as significant a factor in liveborn infants. The present plan of care designed to deal with these problems in liveborn infants at the Boston Lying-in Hospital has been presented.
Schmidt's Syndrome (Thyroid and Adrenal Insufficiency) and Coexistent Diabetes Mellitus
Authors: Solomon Neil , Carpenter Charles C J , Bennett Ivan L , Harvey A McGehee
Published: December 2014

The world literature covering the coincidence of Addison's disease and either diabetes mellitus and/or thyroid aberration has been reviewed.

In addition, ten new patients, eight with idiopathic and two with tuberculous Addison's disease, thyroid dysfunction and diabetes mellitus were studied.

Five of the eight patients with idiopathic Addison's disease showed significant titers ofantiadrenal antibody and six of these eight showed significant titers of thyroid antibodies. However, neither of the two patients with tuberculous Addison's disease showed evidence of antiadrenal antibody, but one exhibited thyroid antibodies.

Patients with idiopathic rather than tuberculous Addison's disease showed a higher coincidence of diabetes mellitus and/or thyroid dysfunction.
Differentiation into Two Types by Measurement of Serum Insulin-like Activity in Vitro
Authors: Steinke Jurgen , Soeldner J Stuart
Published: December 2014

In eleven insulin sensitive and in six insulin resistant diabetic patients, insulin-like activity was measured in unmodified serum and in the corresponding acid ethanol extract shown to be free of insulin antibodies. Whereas most of the insulin responsive and four insulin resistant diabetic patients exhibited a similar ratio of insulin-like activity of serum to the respective serum extract, two patients with insulin resistance exhibited a more than one-hundredfold increase in this ratio.

Of the factors analyzed, i.e., length of insulin treatment, daily insulin dose, maximum serum insulin binding capacity, serum ILA and serum extract ILA, only insulin binding capacity and serum extract ILA exhibited a positive correlation in both the insulin responsive and insulin resistant patients.
Studies of Pulse Wave Velocity in Potential Diabetic Subjects
Authors: Gunn G C , Dobson H L , Gray James , Geddes L A , Vallbona C
Published: December 2014

The arterial pulse wave velocity was studied in seventyfive potential diabetic subjects. A significant increase in the pulse wave velocity was found in the age group of 0 to 10 and 21 to 50 yrs. when compared to an age-related group of normal subjects. Such alterations of the pulse wave velocity have been interpreted as being an index ofdiffuse atherosclerosis and support the concept that early degenerative vascular diseaseoccurs in patients genetically destined to develop diabetes mellitus. Its use as a diagnostic tool and a therapeutic index has also been postulated.
Action of Testosterone on the Mammary Glands of Alloxan-diabetic Rats
Authors: Ahrén Kurt , Angervall Lennart , Arvill Anders
Published: December 2014

Mammary gland development was studied in castrated, alloxan-diabetic rats injected with testosterone. After twentyone days of daily injections with 0.5 mg. testosterone propionate, the mammary glands of the diabetic rats showed extensive lobule-alveolar development which was even more pronounced than in nondiabetic controls injected withthe same dose of testosterone. This result shows that a normal secretion of insulin is not a prerequisite for lobule-alveolar development in the rat mammary gland. The more extensive lobule-alveolar development in the diabetic rats can be explained by a higher production of adrenal steroids in these rats.

From the result of the present investigation and our previous study on alloxan-diabetic rats injected with ovarian hormones it seems likely that there is inadequate production of prolactin in alloxan-diabetic rats.
Modification of Response to the Triamcinolone Glucose Tolerance Test by Treatment with Oral Hypoglycemic Agents Victoriano
Authors: Navarrete Victoriano N , Torres Isabel H , Ayala Luis Castelazo , Alger Carlos R , Flores Homero V
Published: December 2014

(a) From 67 to 87 per cent of the abnormal triamcinolone glucose tolerance curves are improved after treatment with small doses of hypoglycemic drugs.

(b) As the weight reducing diet normalized only 6.6 per cent of the abnormal triamcinolone curves, it is possible to conclude that weight reduction alone is not enough to normalize this test.

(c) The incidence of obstetrical complications (macrosomias, miscarriages, stillbirths, habitual abortion, and congenital malformations) in women with an abnormal triamcinolone test decreases remarkably or disappears after normalization of this test.
Glucose Dynamics in Normal Subjects and Diabetic Patients before and after a Glucose Load
Authors: Forbath Nicholas , Hetenyi Geza
Published: December 2014

The method of successive measured injections of tracer using uniformly labeled C-14-glucose as tracer was applied to determine the pool size, apparent distribution space and the rates of endogenous glucose production and utilization in the fasting state and at twenty to 110 minutes after the intravenous injection of a 0.3 gm./kg. glucose load in six nondiabetic and sixteen diabetic subjects.

The amount of intermixing glucose (“pool”) and the endogenous glucose production in the fasting state were higher in diabetics than in normals. The rate of glucose production decreased after the intravenous injection of the glucose in normals and nonketotic diabetics, but not in three out of four ketotic diabetics.

The average rate of glucose utilization in the fasting state was found to be slightly higher in diabetics than in normals, but it increased to a lesser extent following the injection of glucose. This smaller increase and larger glucose pool are the main causes of decreased glucose tolerance in diabetics.

The exponential slope of the concentration of glucose in the plasma after an intravenous injection of glucose (usually referred to as ‘K’) was not found to be correlated significantly with the rate of glucose utilization.
Coma and Hyperglycemia Following Drinking of Acetone
Authors: Gitelson S , Werczberger A , Herman J B
Published: December 2014

A patient with coma due to drinking of acetone is described. Recovery was followed by hyperglycemia and decreased carbohydrate tolerance persisting for four months. A similar course, although not so prolonged, has been recorded by other authors in poisoning due to inhalation of acetone vapor. Possible mechanisms by which acetone poisoning might affect carbohydrate metabolism are briefly discussed.
Plasma Insulin Responses to Glucose and Tolbutamide of Normal Weight and Obese Diabetic and Nondiabetic Subjects
Authors: Perley Michael , Kipnis David M
Published: December 2014

Plasma insulin responses to oral glucose (100 gm.) and intravenous tolbutamide (1.0 gm.) before and after dexamethasone were determined in normal, obese nondiabetic, normal-weight diabetic and obese diabetic subjects. Fasting plasma insulin levels were significantly higher in obese nondiabetic and obese diabetic subjects than in normalweight nondiabetic and diabetic individuals. Total plasma insulin response to oral glucose in obese nondiabetics was threefold greater, in obese diabetic 2.2-fold greater, and in normal-weight diabetics 1.7-fold greater than that observed in normal individuals. When the plasma insulin responses of obese diabetic and nondiabetic subjects were measured at comparable blood sugar levellN insulin secretion was demonstrated to be significantly impaired in the diabetic group. The initial plasma insulin response (i.e., thirty-minute level) to glucose of diabetic subjects is markedly impaired when compared to normal-weight and obese nondiabetic individuals. Total plasma insulin response to intravenous tolbutamide was fourfold greater in obese nondiabetic and obese diabetic subjects than in normal-weight nondiabetic and diabetic individuals. Following dexamethasone (2 mg. q.i.d. × 2), plasma insulin response to intravenous tolbutamide was increased fivefold in normal subjects, threefold in obese nondiabetics, 1.6-fold in obese diabetics and twofold in nonobese diabetics.

The results of these studies indicate that obesity is associated with a hypersecretory insulin response to both tolbutamide and glucose. The presence of overt diabetes melitus indicates an impairment in insulin response in both obese and nonobese individuals when compared to their appropriate nondiabetic controls. Dexamethasone provokes a marked compensatory insulin response in nondiabetics and makes more apparent the impaired secretory capacity of diabetic subjects. Maturity-onset diabetes in nonobaese individuals appears to be a consequence primarily of insulin deficiency. In obese diabetic individuals, however, even though secretory capacity may be significantly greater than observed in nonobese diabetics, impaired carbohydrate tolerance develops because insulin antagonism associated with obesity per se.
Deamidation of Insulin during Storage in Frozen State
Authors: Berson Solomon A , Yalow Rosalyn S
Published: December 2014

Insulin dissolved in weak HC1 (5×10−3M) appears to undergo progressive deamidation on storage at –15° C. Some commercial solutions of insulin contain quite significant amounts of desamido components. The possibility that desamido insulin may contribute to insulin antigenicity is considered.
Biochemical Studies of “Prediabetes”
Authors: Ricketts Henry T , Cherry Richard A , Kirsteins Lidia
Published: December 2014

Five-hour glucose tolerance (GTT), serum insulin (IRI) response to glucose, glucose tolerance after cortisone (CGTT), tolbutamide tolerance (TTT) with insulin response, free fatty acids (FFA) after fasting and after glucose, blood ketones after fasting, and fractional serum lipids after cortisone were determined in most or all of twenty-five subjects with a strong predisposition to diabetes, twenty-one of them being the offspring of pairs of diabetic parents. Twenty-four healthy subjects with no family history of diabetes served as controls. Although all results except those of the CGTT were within accepted limits of normal, “prediabetics” differed significantly from controls in having higher one-half-hour, one-hour and two-hour blood sugar values and higher IRI levels at one and two hours during GTT, higher blood sugar values at one-half hour, one hour and two hours during CGTT, and smaller and slower depression of blood sugar despite normal insulin response during TTT. No differences in lipid metabolism between the two groups were found except that, surprisingly, the controls had higher FFA after twenty-four-hour fasting than the “prediabetics.” Small but definite deviation in glucose metabolism, and possibly in insulin reponse glucose, remain the most sensitive biochemical indicators to the “prediabetic state,” but their predictive reliability has yet to be ascertained.
Growth Hormone-Insulin Interaction Fact and Speculation
Authors: Rabinowitz D , Merimee T J , Burgess J A
Published: December 2014

The metabolic effects of human growth hormone may be segregated into two classes which can be termed “insulinlike” (or “anabolic”) and “contra-insulin” (or “diabetogenic”). It is proposed that the “anabolic” actions of HGH are optimized by the presence of insulin, whereas the “diabetogenic” actions are dominant in the absence of insulin. In line with this notion, the sequential release of insulin and of HGH which follows protein ingestion, or aminoacid infusion may serve to route aminoacid toward protein, while buffering changes in plasma glucose concentration.
Cation Requirements for Insulin Secretion in the Isolated Perfused Pancreas
Authors: Grodsky Gerold M , Bennett Leslie L
Published: December 2014

The effect of cations on insulin release was studied in the isolated pancreas of the rat perfused with a synthetic perfusate consisting of albumin and buffer. The omission of calcium and magnesium ion completely inhibited insulin release stimulated by glucose. The ionic requirement was specific for calcium ion since perfusates containing calcium but no magnesium permitted normal insulin release by glucose, whereas perfusates containing magnesium but no calcium did not. The presence of only 0.2 mEq. per liter calcium was adequate to permit much, though not all, of the insulin response after glucose to occur. Potassium ion, when raised from 4 to 8 mEq. per liter, directly stimulated insulin release in the complete absence of glucose.
Diabetes and Anterior Pituitary Insufficiency: Final Course and Postmortem Study of a Diabetic Patient with Sheehan's Syndrome
Authors: Poulsen J E
Published: December 2014

The final course and postmortem of a patient with diabetes and anterior pituitary insufficiency are presented. The preliminary report of this case with recovery from retinopathy was published in 1953.

The retinopathy had not reappeared when the patient died in uremia in 1960. From 1951, substitution treatment with cortisone and thyroid was given.

The postmortem was typical for anterior pituitary insufficiency due to postpartum pituitary necrosis (Sheehan's syndrome). The anterior pituitary was mainly substituted by fibrous tissue and the adrenal cortices were atrophic.

Microscopic examination of the eyes did not show obvious signs of diabetic retinopathy after thirty-six years of diabetes and fifteen years after retinal hemorrhages and the onset of pituitary insufficiency. The results of postmortem examination of other organs did not differ from the usual findings in cases of juvenile diabetes dying in uremia.

The advisability of hypophysectomy for the palliation of diabetic retinopathy is discussed, and it is suggested that a closer examination of the influence of growth hormone on retinal metabolism and vascular function may be of interest.

Perhaps the recently demonstrated unmyelinated fibers in the optic nerve coming from the pituitary stalk will be shown to have an influence on the vascular regulation of the retina, and on the pathogenesis of retinopathy; if so, these fibers may explain why only the retinopathy and not the other late manifestations of diabetes seem to benefit from ablation of pituitary function.
A Survey for Unknown Diabetics in a Mental Hospital: I. Men under Age Fifty
Authors: Waitzkin Leo
Published: December 2014

A 100-gm., two-hour, oral glucose tolerance test was given to an institutional group of 359 mentally ill men under age fifty without known diabetes. The test was selectively repeated. In 11.7 per cent of the group, results were interpreted, in association with other data, as being consistent with previously unknown, unsuspected diabetes. It occurred more frequently among the older, the overweight and those with diabetic relatives, resembling the prevalence of known diabetes in the general population. The relatively high incidence of previously unknown diabetes that was discovered in the group is ascribed to their age range, commonness of overweight and the method of study.

Further investigation is required to determine if prolonged phenothiazine therapy may be a contributory diabetogenic influence.
Clinical Use of Diazoxide and Mechanism for Its Hyperglycemic Effects
Authors: Graber Alan L , Porte Daniel , Williams Robert H
Published: December 2014

The mechanism of diazoxide hyperglycemia in man has been studied by measurement of serum glucose, immunoreactive insulin, and plasma free fatty acids. In a patient with islet cell carcinoma, in normal subjects, and in diabetic patients, diazoxide hyperglycemia was accompanied by a decrease in serum immunoreactive insulin, an increase in plasma free fatty acids, tachycardia, and a widened pulse pressure. The similarity of these effects to those produced by epinephrine has suggested that at least some of the effects of diazoxide may be mediated by endogenous sympathetic stimulation. Diazoxide has been used successfully to control hypoglycemia in a patient with islet cell carcinoma for twenty months.
The Duration of Unrecognized Diabetes Mellitus
Authors: Anderson T W
Published: December 2014

If the age specific prevalence rates for known and unrecognized diabetics are known, deduction can be made of the rates at which cases are moving in and out of these categories and, therefore, the average time spent in each category. For example, if between the age of forty and fifty the number of known diabetics in a population increased from 300 to 600, then the increase (300 over ten years) indicates that previously unrecognized diabetics have become recognized at an average rate of thirty per year. Similarly, if the number of unrecognized diabetics has in-creased from 400 to 900, the unrecognized group has been increasing at an average rate of fifty per year. If the rate at which death has been removing persons from each group is known, it is possible to form a theoretical model and calculate approximately how long a person is likely lo remain in the unrecognized category.

When the calculations are carried through, it appears that the average length of time spent in the unrecognized category is of the order of ten to twelve years. Unfortunately, some of the steps in the calculations are based on unknown factors, and in assuming arbitrary values for these factors, there will be some error introduced into the final estimate. Since the method of calculation may be of interest and value, however, the argument will be presented in detail.

When a new case of diabetes mellitus is diagnosed, it is not known how long the disease has been present. In this paper an attempt is made to deduce from epidemiological data the average length of time between development of impaired carbohydrate tolerance and diagnosis.
Histological and Autoradiographic Studies of the Islets of Mice Injected with Insulin Antibody
Authors: Logothetopoulos J , Bell E G
Published: December 2014

Young adult male mice were injected intraperitoneally twice daily with the globulin fraction of anti-insulin sera. Control mice received injections of the same fraction from guinea pigs immunized with Freund's adjuvant only. Blood glucose levels in the mice injected with insulin antibodies were continuously maintained over 250 mg. per 100 ml.

Mice were killed before and at 1, 3, 6, 10 and 15 days after the injections started. Thymidine-H-3 was injected subcutaneously two hours before killing. The following observations were made:

(1) Beta cells quickly lost their granules and remained degranulated throughout the period of injections of insulin antibodies. Swelling of the Golgi complex and other histological evidence of increased cellular activity were present. Neutrophils, eosinophils and monocytes accumulated around the islets in the mice injected with antibody.

(2) In the control mice the number of labeled beta cell nuclei (radioactive index) ranged from seven to twenty-five per 3,000 nuclei of beta cells. Labeled beta cells were scattered throughout the islets. Alpha cells showed a lower radioactive index, one to three per 1,000 nuclei.

In the mice injected with antibody the radioactive index was within the normal range on the first day, reached a peak in mice killed on the third day and subsequently progressively declined in spite of the sustained hyperglycemia.
Observations on Small Blood Vessels of Skin in the Normal and in Diabetic Patients
Authors: Friederici H H R , Randolph Tucker W , Schwartz Theodore B
Published: December 2014

To obtain data on the relative incidence of changes in the basement membrane of small peripheral blood vessels in diabetic and nondiabetic patients, a “blind” study of skin biopsies was undertaken. Parallel to a thorough clinical and laboratory work-up, punch biopsies of skin were obtained under local block anesthesia. A number of morphological features were analyzed by light and electron microscopy and graded on a semiquantitative scale, and the basement membrane was measured with calipers. The tabulated data were then correlated with clinical information. The following conclusions may be drawn:

(a) “Capillaries” of the dorsal skin of the finger revealed a more complex structure than that seen in capillaries of muscle or loose connective tissue. This increased complexity was mainly due to incomplete reduplication of the endothelial cell wall by long abluminal cytoplasmic extensions.

(b) The fine structure of the basement membrane as well as its thickness revealed very large variations, having one of the following appearances:

(1) Homogeneous or finely fibrillar, and thin

(2) Homogeneous or finely fibrillar, and thick

(3) Finely fibrillar and lamellated

(4) Containing inclusions.

(c) Careful, unbiased evaluation of “capillaries” of control patients without family or own history or chemical evidence of diabetes and who can reasonably be classified as normal, and of diabetic patients, leads to results permitting no distinction between the two groups. No differences could be seen regarding the number of endothelial and/or pericytic cells per “capillary,” state of vascular contraction or dilatation, cytologic detail, or type or width of the basement membrane between normal controls and diabetic patients.

(d) The reasons for the variations in basement membrane thickness and appearance and in cellular structure are not known, but diabetes can probably be excluded as a specific etiologic factor.

(e) The results of this investigation again underline the importance of “blind” studies with adequate controls, especially where subjective evaluation cannot be excluded.

(f) It may be advisable to conduct similar blind studies on other capillary territories to assess in an unequivocal manner the relationship between the appearance of the endothelium and the basement membrane and specific diseases.
Lack of Influence of Insulin-induced Hypoglycemia on Alimentary Hyperglycemia
Authors: Chester Edward M , Travis Randall H , Mackenzie Malcolm S
Published: December 2014

Studies were designed to determine the effect, in diabetic patients, of insulin induced hypoglycemia upon alimentary hyperglycemia. The following results were obtained.

1. In a four-hour study, as a control day, each of four patients was given his usual insulin one hour before the oral administration of 100 gm. of glucose. On another occasion, under identical conditions, hypoglycemia was produced during the hour preceding glucose administration, by intravenous administration of Crystalline Insulin. There was no greater impairment of glucose tolerance during the subsequent three hours than noted in the control study.

2. In ten patients, maintained on constant diets for three consecutive days, blood sugars were determined at frequent intervals from 7 a.m. to 10 p.m. each day. Each patient, if insulin dependent, received his usual dose before breakfast on all three days. On the second day the administration of additional subcutaneous Crystalline Insulin produced hypoglycemia during the forenoon. No carbohydrate supplementation was given and generally the hypoglycemia was corrected only by lunch given at the usual time. The postprandial blood sugar elevations for the balance of that day and throughout the third day were no greater than those of the first or control day.

3. In one patient six identical studies were performed. In each instance 25 gm. of glucose was given by mouth at 7 a.m. on each of three consecutive days. Blood sugars were measured at two-hour intervals from 8 a.m. to 12 noon. On day two hypoglycemia was produced by the administration of 15-25 U. Crystalline Insulin after the 8 a.m. blood specimen was drawn. Although mean blood sugars were statistically significantly higher on day three than on day one at 8 a.m. and 12 noon, the quantitative measurement of urine sugar showed no increase over that of the control day on either the day of hypoglycemia or the following day.

These data do not support the concept, in patients with diabetes mellitus, that hypoglycemia is followed by further impairment of glucose tolerance.
Diazoxide-induced Diabetes Mellitus in a Hypopituitary Dwarf
Authors: Drash Allan , Wolff Frederick , Langs Harold , Blizzard Robert M
Published: December 2014

The successful application of the well-documented hyperglycemic effect of diazoxide to the management of hypoglycemic states has been previously reported. The present report describes the response of a hypopituitary dwarf to diazoxide administration. Diabetes mellitus, complicated by ketosis, was rapidly induced. Discontinuation of diazoxide therapy was followed by clearing of diabetes over the next five days. A comparison of the diazoxide response of this child to that of a child with leucine sensitivity is made. The possible mechanisms by which diazoxide induces hyperglycemia are discussed.
Serum Proteins of Chinese Hamsters and Response of Diabetics to Tolbutamide and Insulin
Authors: Gerritsen G C , Dulin W E
Published: December 2014

Fifty young hamsters with elevated, two-band type α-2 serum proteins were studied for development of glycosuria for two years. During this observation period, none of these animals developed glycosuria. These results did not support the suggestion that the quantitative and qualitative changes in α-2 proteins correlate with prediabetes in the Chinese hamster.

Serum protein patterns have been run on fifty diabetic and ninety-six normal animals. Three types of patterns have been found: three α-2 protein bands, two bands, and a type which appears to be intermediate between the three-and two-banded types. No significant difference in the incidence of various α-2 types was found between diabetics and nondiabetics. Since many animals with elevated α-2 protein with two bands do not develop glycosuria and α-2 patterns of diabetics do not differ from nondiabetics, it is concluded that in the Upjohn colony α-2 proteins cannot be used as markers for diabetes.

The only criterion available for distinguishing “diabetics” from “nondiabetics” is glycosuria. Mild diabetic animals respond to tolbutamide with a reduction in glycosuria but severe diabetics do not. Therefore, diabetic hamsters are similar to diabetic humans in responsiveness to tolbutamide.
The State of Insulin in Human Plasma
Authors: Martin Julio M
Published: December 2014

In plasma obtained from normal fasting subjects insulin was precipitated by anti-insulin serum. Both the precipitate and the supernatant were extracted with acid-alcohol. Insulin or insulin-like activity was measured in the extracts by immunoassay, glucose uptake by the rat hemi-diaphragm and CO2 production by the rat epididymal fat pad. The amount of insulin found in plasma before extraction was quantitatively recovered from the insulin-anti-insulin precipitate extracted with acid-alcohol as measured by the immunoassay. No insulin was detected in the extracted supernatant. In close agreement were the results obtained with the diaphragm. Only the adipose tissue was able to demonstrate ILA in the extracted supernatant. This ILA was present even in control samples (buffer with known amounts of Crystalline Insulin added) in spite of the fact that all the added insulin had been recovered in the precipitate.

These results suggest that in normal human plasma all the insulin is readily available to react with insulin antibodies. Results with the epididymal fat pad method stroagly suggest the possibility that factors other than insulin stimulate the production of CO2 from glucose.
Studies on the Mechanism of Insulin Antagonism by Albumin in Rat Diaphragm
Authors: Davidson Mayer B , Goodner Charles J
Published: December 2014

Utilizing a modification of the rat diaphragm technic, studies of the mechanism of action of the albumin-associated antagonist were carried out using human fraction V. It was demonstrated that the antagonist could not be washed off of the diaphragm, that prior exposure of the diaphragm to insulin did not fully protect it from subsequent antagonism of the insulin effect and that, although antagonism was proportional to albumin concentration, large excesses of insulin could not completely overcome small concentrations of the antagonist. The intracellular accumulation of AIB was inhibited by the antagonistic albumin but not by a nonantagonistic one (bovine fraction V). Both albumins depressed radioactive glycine incorporation into muscle protein. The antagonist was shown to inhibit glucose uptake much more than glycogen synthesis.

These data indicate that the albumin-associated antagonist primarily blocks insulin effects on transport by either an extremely strong binding to the muscle cell or an irreversible alteration of the diaphragm's response to insulin without binding.
Hepatic Glucose Phosphotransferases Variations Among Species
Authors: Lauris V , Cahill G F
Published: December 2014

Glucokinase activity (ATP :D-glucose-6-phosphotransferase, E.C. 2.7.1.2) was assayed in various species, including man (Homo sapiens). Low or absent activities were found in the toadfish (Opsanus tau) cat (Felis domesticus), guinea pig (Cavia porcellus), calf (Bos taurus), and man, and higher activities in the bullfrog (Rana catesbeiana), dog (Canis familiaris), rabbit (Oryctolagus cuniculus), mouse (Mus musculus), rat (Rattus norwegicus), and sand rat (Psammomys obesus). Fasted mice and dogs failed to show a decrease in activity. Sand rats with spontaneous diabetes or rendered diabetic by diet also failed to show a reduction in activity. The role of the enzyme in the regulation of blood glucose concentration remains speculative.