bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies on Mechanism of Glucose Synthesis in Diabetic and Normal Rat Liver
Authors: Wagle SR
Published: December 2014

Glucose synthesis and enzymatic activities of various CO2-fixing enzymes have been studied in normal and diabetic liver preparations. A three-fold increase in pyruvate carboxylase and α-ketoglutarate carboxylase has been observed in alloxan-diabetic, anti-insulin serum and cortisol treated liver preparations as compared to normal. The increased glutarate carboxylase activity was found to be localized in the mitochondrial fraction. In addition a sixfold increase in phosphoenolpyruvate carboxykinase was observed. Studies on net glucose synthesis show that combination of pyruvate and glutamate are far more effective than any single substrate. Furthermore, oxaloacetate utilization was found to be increased in diabetic and cortisol treated rat livers. Based on these results a pathway for gluconeogenesis has been formulated. It is suggested that increased gluconeogenesis observed in diabetic animals involves CO2 fixation with pyruvate and glutamate giving rise to increased formation and utilization of oxaloacetate.
Effect of Glucagon on the Metabolism of Lipids and on Urea Formation by the Perfused Rat Liver
Authors: Penhos J C , Wu C H , Daunas J , Reitman M , Levune R
Published: December 2014

Livers obtained from fed or fasted rats were perfused with blood from fasted rats with and without the addition of glucagon and/or a hyperlipemic serum (HLS).

In addition to its well-known hyperglycemic effect, glucagon increased the blood levels of the ketone bodies and of urea, and decreased the levels of cholesterol, total lipids and NEFA.

The magnitude of the effects noted were dependent upon the previous state of the liver and the addition of the hyperlipemic serum.

In the fed liver, glucagon produced a greater degree of hyperglycemia than in the fasted liver and this effect was enhanced by the addition of a hyperlipemic serum. In fasted livers the addition of a hyperlipemic serum did not increase the hyperglycemia produced by glucagon alone.

Total lipids, cholesterol and NEFA were decreased when glucagon was added to either the fasted or fed liver, in the presence or absence of a hyperlipemic serum. Glucagon caused a greater increase in the level of ketone bodies in the fasted than in the fed liver and this effect was increased by the addition of a serum rich in lipids.

The addition of glucagon caused an increase in the levels of urea and this effect was reduced when a hyperlipemic scrum was acMted.
Studies of “Bound” Insulin by Epididymal, Fat Pad Assay
Authors: Gener-Segui Juan , Wolfe Ava J
Published: December 2014

Sera were treated with Dowex-50 W resin and the fraction which escaped adsorption, and that which was adsorbed and subsequently eluted, were assayed for insulin-like activity (ILA) using the rat epididymal fat pad technic. Previous investigators have stated that these two fractions contain, respectively,“free” and “bound” insulin.

In individual normal and diabetic sera assayed by thismethod, the “free” fraction accounted for all of the ILA present in the original whole serum. “Bound” insulin was detectable in small quantities when measured by incorporation of glucose-1-C-14 into C-14-O2, but not by incorporation into glycogen. The addition of an adipose tissue extract did not increase the ILA of the eluate nor modify it so that it was neutralized by an anti-insulin serum.

A lyophilized resin eluate from pooled fasting normal human sera, stated to contain “bound” insulin, also had a low level of ILA. This activity did not increase after acid alcohol extraction or at pH 9.8. It was not neutralized by anti-insulin serum either before or after these treatments.

These experiments do not support the concept of a “bound” insulin.
Effect of Insulin Infusion of Pancreas on Blood Glucose
Authors: Colwell John A , Colwell Arthur R
Published: December 2014

Glucagon-free insulin in doses of 0.003 to 0.2 units per kilogram of body weight was infused into the pancreatic artery and portal vein during anesthesia or in fully recovered dogs. The changes in blood glucose concentrations were not significantly different between the two sites of infusion with any of the doses employed. These data indicate that insulin does not affect endogenous insulin secretion by a direct pancreatic mechanism. It may operate by reducing the blood glucose or via some other metabolic change. Similar experiments were conducted with glucagon (0.2 μg.) in anesthetized dogs. Glucagon infusion into the pancreas or liver failed to affect insulin or glucagon secretion as evidenced by peripheral venous glucose response.
Effect of Tolbutamide on Renal Glucose Reabsorption
Authors: Henningsen Per , Benveniste Daniel
Published: December 2014

In sixteen patients, thirteen examinations were carried out after intravenous administration of 1 gm. of tolbutamide, including measurements of insulin clearance and glucose TmG before and after administration. Furthermore, four examinations were performed with administration of 1 gm. of tolbutamide daily over periods from fourteen days to 160 days. No alterations in insulin clearance were found. The changes in glucose TMGpresented fairly large individual variations and increases between 20 and 30 per cent were observed in a few patients. An average increase of 9.1 per cent was found after intravenous administration and of 4.8 per cent after oral administration. These variations are not significant.
Diabetic Visceral Neuropathy: A Case Report
Authors: Midtgaard Knud
Published: December 2014

A case report is presented concerning a long-standing, juvenile-type diabetic with severe vascular involvement and severe diarrhea and steatorrhea. In spite of this, light and electron microscopic investigations of a peroral jejunal biopsy did not show any signs of diabetic microangiopathy, i.e., thickening of the basement membrane of the subepithelial capillaries.

It appears that diabetic microangiopathy can be ruled out as an immediate etiologic factor in diabetic diarrhea.
L-Leucine in Secondary Sulfonylurea Failure
Authors: Rifkin Harold , Podolsky Stephen , Ross Herbert , Conason Emil G , Most Sylvia
Published: December 2014

Ten diabetic patients, secondary failures to sulfonylureas, seven of whom were receiving maximal doses of tolbutamide and three of chlorpropamide, were concurrently given L-leucine, as tablets, in a daily dosage of 12 gm. for four to eight weeks. Good diabetic control, with most blood glucose values below 130 mg. per 100 ml., was achieved in three; a good response, as indicated by a fall in blood glucose values of 20 per cent or more, occurred in eight; two patients did not respond. Of four patients receiving thiazide, which might have contributed to their secondary failure, three responded. Reversal of osmotic diuresis and symptoms of nocturia occurred in five patients. No untoward effects of any significance were noted. Adjunctive use of L-leucine for better diabetic control in patients who have become refractory to sulfonylureas, or are receiving thiazides, is suggested.
On Insulin 1-131 Metabolism in Mice: Modifying Effects of Anti-insulin Serum and of Total Insulin Dosage
Authors: Beck Lyle V , Zaharko Daniel S , Oberts Nancy , King Christine
Published: December 2014

Estimations have been made on abilities of certain tissues of mice injected intravenously with insulin I-131 to concentrate and degrade this compound; change of I-131 from TCA insoluble to TCA soluble form has been used as measure of degradation. Insulin I-131, estimated as TCA insoluble I-131, was concentrated by liver and especially by kidney; formation of TCA soluble I-131 occurred most rapidly in liver. With insulin I-131 held constant but total insulin progressively increased, concentration ratios for TCA insoluble I-131 progressively increased in kidney, and decreased in other tissues. In all tissues, conversion of I-131 from TCA insoluble to TCA soluble form decreased progressively with increase in total insulin. Prior mixing of insulin I-131 with excess guinea pig anti-insulin serum (AIS) resulted in loss of tissue abilities to convert the I-131 into TCA soluble form, and in loss of abilities of all tissues other than liver to concentrate this TCA insoluble I-131.
Peripheral Neuropathy in Juvenile Diabetes
Authors: Gamstorp I , Shelburne SA , Engleson G , Redondo D , Traisman H S
Published: December 2014

In order to study the incidence of diabetic peripheral neuropathy in children, nerve conduction studies and complete neurological examinations were performed on 107 unselected diabetic children below seventeen years of age. Motor conduction velocity of the ulnar, median, and peroneal nerves and sensory “conduction velocity” of the median nerves were measured by electromyographical technics. On the basis of the results of the electrophysiological and neurological examinations, eleven patients were considered to have definite evidence of peripheral nerve disease, twenty-three had equivocal findings, and seventy-three had no demonstrable abnormalities. The diabetic children with definite evidence of peripheral neuropathy had a longer duration of diabetes mellitus, a later age at onset of the disease, and were older at the time of examination than those patients without evidence of peripheral nerve disease. Those children with neuropathy were also thought to have poorer control of diabetes than those without neuropathy, but this was difficult to evaluate because of the interrelationship of the control factor with the duration of the disease. Three patients were found to have diabetic angiopathy; one had unequivocal, one equivocal and one no signs of neuropathy.
Effect of Selected Hexoses, of Epinephrine and of Glucagon on Insulin Secretion in Man
Authors: Karam John H , Grasso Sebastiano G , Wegienka Laurence C , Grodsky Gerold M , Forsham Peter H
Published: December 2014

Immunochemical methods of measuring serum insulin have implemented studies in man confirming in vitro data which suggest that metabolizable sugars such as mannose and glucose cause insulin secretion, whereas galactose, a nonutilizable sugar, does not. Infusions of 2-deoxy-D-glucose are associated with greatly increased epinephrine secretion and sustained hyperglycemia, but no rise in serum insulin levels. Epinephrine infusions induce and prolong hyperglycemia without raising serum insulin levels and effectively inhibit insulin secretion during glucose administration. These findings agree with in vitro evidence that epinephrine directly inhibits pancreatic secretion of insulin. Glucagon, on the other hand, sharply stimulates insulin secretion, either alone or after glucose infusions. Data are presented which suggest that this may be a direct effect of glucagon on the release of insulin by the pancreatic beta cell.
Preventive Action of the Monoaminooxidase Inhibitor, Nialamide, on Experimental Diabetes in Rats
Authors: Buschiazzo Perla Mordujovich de , Buschiazzo Héctor O , Bosch Ricardo , Rodríguez Ricardo R
Published: December 2014

Intraperitoneal injection of nialamide in rats submitted to extensive pancreatectomy delays the appearance of diabetes and diminishes its intensity. Whereas in the control group, some of the animals developed diabetes two to three months after surgical extirpation of the pancreas, the nialamide-treated animals presented diabetes only after five or six months. Neoformation of B cells was observed in these animals, but it was not statistically significant.

Protection against development of diabetes has been observed in all animals which were injected with nialamide immediately before or twenty minutes before alloxan administration.

The antitoxic effect of nialamide, which produces a marked decrease in mortality, has been observed.

Protective action on diabetes might be due to a chemical combination of nialamide with alloxan, thus preventing its action or protecting important enzyme centers. Another possibility might be that nialamide increased circulating catecholamines, especially epinephrine and norepinephrine, producing splanchnic vasoconstriction and diminution of alloxan concentration at the pancreatic beta cells, an effect that was eliminated when an adrenolitic agent was given simultaneously.
Effect of Alcohol on Glucose Production and Lactate, Pyruvate and Ketone Body Metabolism by the Isolated Perfused Rat Liver
Authors: Kreisberg Robert A
Published: December 2014

The purpose of these experiments was to determine whether the effect of ethanol on glucose production could be dissociated from its effect on the cytoplasmic DPN/DPNH ratio in the presence of adequate substrate. Isolated rat livers were perfused with a Krebs bicarbonate Ringer buffer containing 4 per cent albumin and 10 mM alanine in the presence of increasing concentrations of ethanol. Lactate, pyruvate, B-hydroxybutyrate and acetoacetate were used to reflect the cellular redox state. Despite producing maximum changes in lactate, pyruvate and ketone body metabolism, 10 mM ethanol did not inhibit glucose production. Ethanol concentrations of 20 and 40 mM produced no further change in the production of lactate and pyruvate but significantly inhibited ketone body and glucose production by the isolated perfused rat liver. These results are compatible with the proposal that increased entry and intramitochon-drial oxidation of DPNH which results from alcohol metabolism inhibits oxidation of fatty acids, acetyl CoA generation and subsequently gluconeogenesis.
Preventive Action of Tranylcypromine on Alloxan Diabetes in Rats
Authors: Buschiazzo Héctor O , Buschiazzo Perla Mordujovich de , Hernández Rodolfo E , Rodríguez Ricardo R
Published: December 2014

The intraperitoneal injection of tranylcypromine (25 mg./kg.) twenty minutes before the intravenous administration of alloxan prevents the onset of diabetes in the rat. The same protective effect is observed when the monoamine-oxidase inhibitor is injected intravenously (10 mg./kg.) fifteen seconds before alloxan. When these two drugs are mixed in vitro and injected intravenously, the protection disappears.

This protective action against diabetes appears to indicate that tranylcypromine protects important enzymatic centers against the action of alloxan at the pancreatic level.
Suppressive Action of Epinephrine on the Diabetogenic Effect of Alloxan
Authors: Carrasco-Formiguera R
Published: December 2014

The mechanism by which a previous injection of epinephrine blocks the diabetogenic action of alloxan is unknown. The experiments carried out in this study indicate that (a) dihydroergotamine blocks the suppressive action of epinephrine on the diabetogenic effect of alloxan, and (b) in comparable doses, norepinephrine does not exhibit the same effect as epinephrine. The findings are discussed in terms of two alternate mechanisms:(1) Vasoconstrictive effects decreasing the quantity of alloxan reaching the islet; and (2) direct effects of epinephrine on beta cell function.
Triglyceride Metabolism in the Alloxan-Diabetic Rat
Authors: Brown David F , Daudiss K , Durrant J
Published: December 2014

Diabetes mellitus of graded severity was produced by withdrawing insulin from alloxan diabetic rats previously maintained on Protamine Zinc Insulin. The tissue distribution of H-3 palmitate-labeled chyle in the diabetic animals and in normal animals was compared fifteen minutes after its intravenous administration. Although hyperglycemia wasapparent forty-eight hours after insulin withdrawal, it was only at seventy-two and ninety-six hours after insulin withdrawal that marked retention of radioactivity was apparent in blood and that adipose tissue, carcass and hepatic uptake of fatty acid was lower thannormal. Lipoprotein lipase content of epididymal fat pads was significantly higher than normal in insulin-treated and lower than normal in the insulin-deprived rats. The findingsindicate that insulin withdrawal in the alloxan diabetic rat results in delayed clearing of intravenously administered chylomicrons from blood. Initially this may be related in part to the defective uptake by adipose tissue which becomes depleted of lipoprotein lipase. More prolonged insulin deprivation, however, leads to a greatly expanded serum triglyceride pool which in itself could account for the markedly delayed clearing of chylomicrons in severe diabetes.
Effect of Vagotomy and Vagal Stimulation on Insulin Secretion
Authors: Frohman Lawrence A , Ezdinli Ediz Z , Javid Rouhollah
Published: December 2014

The influence of the vagus nerve on insulin secretion in the dog has been confirmed by studies involving both vagotomy and vagal stimulation. Following vagotomy, a fall in portal vein insulin levels occurs. Following stimulation of both the right and left vagus, insulin levels rise abruptly, peak within five minutes and rapidly return to baseline levels. A small rise in blood glucose, which occurs simultaneously, cannot be blocked by phentolamine, an alpha-adrenergic blocking agent. When given alone, phentolamine stimulates insulin secretion. Atropine inhibits both the glucose and insulin rises following vagal stimulation. Only a portion of releasable insulin appears to be under vagal control. Glucose mediated insulin release and net glucose utilization are not significantly affected by vagotomy.
Glomemlar Ultrastructure in Secondary Diabetics and Normal Subjects
Authors: Ireland J T , Patnaik B K , Duncan L J P
Published: December 2014

Renal biopsy tissue obtained from nine nondiabetic subjects and ten patients having diabetes secondary to primary pancreatic disease was studied by light and electron microscopy. The technic for measurement of the basement membrane thickness at the periphery of the glomerular capillaries is described. In seven of the secondary diabetics the capillary basement membrane thickness exceeded 3,500 Å, a width greater than the mean value in the healthy control group by more than two standard deviations. Changes in cellular ultrastructure were also observed. These findings suggest that microangiopathy occurs more frequently in secondary diabetics than has hitherto been conceded and support the view that at least one of the primary causes of basement membrane changes is the metabolic disturbance consequent upon inadequate insulin activity.
Use of Enzyme Proteolysis for the Immunochemical Measurement of Insulin
Authors: Mitchell M L , Byron John
Published: December 2014

An immunochemical assay has been designed that utilizes the catalytic properties of glutathione-activated ficin to separate antibody-bound radioinsulin from unbound insulin I-131. Both the recovery of human insulin added to serum and the failure to detect chemically inactivated insulin provide evidence for the precision and specificity of the procedure. Measurements of endogenous insulin in serum (diluted 1:10) made after the administration of glucose or tolbutamide revealed rapid increases in circulating levels of hormone in nondiabetic subjects. The successful application of enzyme hydrolysis as the basis of a reliable and rapid immunoassay for insulin suggests that with the appropriate antibody and labeled antigen, the same principle could be employed to measure concentrations of other hormones or substances that are potentially antigenic.
A New Oral Hypoglycemic Agent: l-Methyl-4-(3-methyl-5-isoxazolyl)pyridinium Chloride
Authors: Riggi S J , Blickens D A , Boshart C R
Published: December 2014

Oral administration of l-methyl-4-(3-methyl-5-isoxazolyl). pyridinium chloride (I) significantly decreased blood glucose concentration in cockerels, guinea pigs, normal mice and alloxan-hyperglycemic mice and rats. Alloxanized mice were most sensitive to the hypoglycemic action of I. These data indicate that I is an oral hypoglycemic agent in several species of experimental animals both in normo- and hyperglycemic states.
Magnesium Deficiency and Sugar Transport in Muscle: Effect of Acute Insulin Deficiency
Authors: Kahil M E , Simons E L , Brown H
Published: December 2014

Intact diaphragms from magnesium (Mg) deficient rats had an increased 2-deoxyglucose (2-DG) uptake from Mg free medium. Acute insulin deficiency induced by the administration of anti-insulin serum did not inhibit transport.

Addition of Mg to the incubation medium reversed the increased 2-DG transport. Transport as a function of the external 2-DG concentration conformed to Michaeles-Menten kinetics; Mg and insulin deficiency lowered the transport Km with no change in the Vmax Both saturation kinetics and competitive inhibition were demonstrated during the acceleration of sugar transport, while studies with L-glucose and L-arabinose showed no facilitation of nonspecific diffusion of sugar into muscle cells.

These studies indicate that the carrier system is preserved in diaphragms from Mg and insulin deficient rats and accounts for a major portion of 2-DG transport. They also suggest that in Mg deficiency enhanced 2-DG penetration occurs both by an insulin independent and by an insulin sensitive mechanism.
The Sorbitol Pathway: Enzyme Localization and Content in Normal and Diabetic Nerve and Cord
Authors: Gabbay Kenneth H , O'Sullivan John B
Published: December 2014

The enzymes of the sorbitol pathway, aldose reductase and sorbitol dehydrogenase, were investigated in sciatic nerve and spinal cord. The substrate specificities of spinal cord aldose reductase indicates that it is a variant of TPN L-hexonate dehydrogenase which possesses poor polyol forming ability. In contrast, the cauda equina and sciatic nerve aldose reductase have a true aldose reductase with considerable polyol forming ability. The distribution of the latter enzyme is associated with the presence of Schwann cells. Wallerian degeneration experiments are compatible with the localization of true aldose reductase in the Schwann cell and sorbitol dehydrogenase in the axon. There was no change in the levels of sorbitol dehydrogenase in diabetic nerves, a 30 per cent decrease occurred in the aldose reductase content. This decrease suggests a metabolic abnormality of the Sehwann cell, possibly resulting from alrered cellular integrity, which may have important implication for the otiology of diabetic neuropathy.
Failure of Diazoxide to Affect Carbohydrate Metabolism of the Isolated Liver
Authors: Sokal Joseph E
Published: December 2014

It has been reported that diazoxide stimulates hepatic glycogenolysis and inhibits hepatic glucose uptake. In order to determine whether these effects reflect direct action of the drug on the liver, the effect of diazoxide on the isolated perfused rat liver was investigated. Exposure of glycogen-containing livers to concentrations of diazoxide as high as 180 μg./ml. for as long as four hours did not result in decrease in liver glycogen, increase in hepatic glucose output, or increase in urea production. Diazoxide did not inhibit glucose uptake and glycogen deposition by glycogendepleted livers presented with glucose loads. It is concluded that direct action on the liver is not a contributory mechanism to the diabetogenic effect of diazoxide.
Functional Microangiopathy in Diabetes Mellitus
Authors: Ditzel Jørn
Published: December 2014

The present knowledge of the state of the microvasculature in diabetic subjects early during the course of the disease and prior to any clinical signs of retinopathy and nephropathy is reviewed. Functional changes in the peripheral vascular bed have been demonstrated by various methods in the retina, the skin and the conjunctiva. The common features of these functional changes appear to be a loss of normal vascular tone and increased permeability. There is also evidence of a functional disorder of the glomerular capillaries in young diabetics early during their disease, as indicated by increased glomerular filtration rates.

Based on the presence of a functional microangiopathy, a dynamic concept of the development of clinical microangiopathy is presented. It is suggested that the functional changes may occur very early and might in some instances come before the degenerative vascular changes. Thus they might participate in the mechanism of the development of the long-term diabetic syndrome.
Hypoglycemic Effect of Adipose Tissue Extracts (ATE) in Rats
Authors: Lenti G , Pellegrini A , Pagano G , Zizi P , Cirillo R , Mascia V , Rossi Miss O
Published: December 2014

Intraperitoneal administration of ATE obtained from pooled epididymal fat pads produced hypoglycemia in adrenalectomized rats. Injection of extracts from rat brain, liver and muscle did not affect the blood glucose levels of the adrenalectomized animals. With high ATE concentrations, a progressive decline in blood sugar was observed and most of the animals died from hypoglycemia ten to thirteen hours after intraperitoneal injection.Identical concentration of ATE did not affect the blood glucose levels in intact rats.

In some adrenal ectomized rats injected with ATE (100 mg.) a progressive bound insulin fall was detected, but no significant change in free insulin was evidenced.
Effect of Biguanides on Intestinal Absorption of Glucose
Authors: Czyzyk Artur , Tawecki January , Sadowski Jan , Ponikowska Irena , Szczepanik Zdistawa
Published: December 2014

In a group of fifty-eight patients with mild maturity onset diabetes, the double oral glucose loading test after StaubTraugott, the intravenous glucose loading test with calculation of the glucose disappearance rates and intraduodenal glucose loading test were performed before and after phenethylbiguanide administration. The drug produced no changes in the intravenous glucose loading test, whereas it caused a significant lowering of the glycemia curves obtained in oral and intraduodenal loading tests. In order to complement these investigations, double fistula of the initial and distal segment of the small intestine were made in six dogs and perfusion of the intestine performed in situ with a glucose solution. Previous administration of butylbiguanide produced a marked flattening of the glycemia curve, and the recovery of glucose from the distal segment of the small intestine was more than doubled.

Suppression of intestinal glucose absorption by biguanide derivatives, demonstrated in the present study, could be explained by specific action of these compounds on the small intestine wall. Biguanide derivatives, accumulated in intestinal cells in higher concentrations than in other tissues, could impair glucose utilization by suppressing the synthesis of ATP required for active absorption of glucose.
Effect of Glycodiazine on Blood Sugar in Diabetes Mellitus
Authors: Choi Young , Kreines Kenneth
Published: December 2014

Clinical trials were made with glycodiazine, N.(5(2-Methoxyethoxy)-2-Pyrimidinyl) benzenesulfonamide by a technic in which the effects of the drug were compared statistically to those of a placebo in a group of patients with the adult onset type of diabetes mellitus. Glycodiazine was active orally at two dosage levels 0.5 gm. b.i.d. and 0.5 grn. once a day although onset of antihyperglycemic response was slower with the smaller dose. No untoward side effects were noticed. The findings indicate that glycodiazine may be an effective oral antihyperglycemic agent.
Biological Properties of a Transplantable Islet-cell Tumor of the Golden Hamster: III. Electron Microscopic Studies
Authors: Simar Léon J , Sodoyez Jean C , Grillo T Adesanya Ige , Nagano Toshio , Lefebvre Pierre J , Foa Piero P
Published: December 2014

This paper describes the ultrastructure of a transplantable islet cell tumor of the hamster. No ultrastructural similarities with normal A or B pancreatic cells were noted. Signs of active metabolism and protein synthesis are the outstanding features of this tumor. The absence of typical β granules and the presence of some peculiar structures are discussed in the light of the demonstrated insulin-producing property of the tumor.
Effect of Blood Glucose on Glucagon Secretion in Anesthetized Dogs
Authors: Buchanan Keith D , Vance James E , Dinstl Karl , Williams Robert H , Hickernell Barbara , Page Susan
Published: December 2014

Insulin induced hypoglycemia and tolbutamide administration accompanied by much smaller falls in blood glucose were associated with increased pancreatic vein IRG concentrations in laparotomized dogs under barbiturate anesthesia. Hyperglycemia may have diminished pancreatic IRG release. Changes in IRG levels in peripheral and jejunal veins during hypoglycemia were unremarkable. In dogs, pancreatectomy was associated with no change in IRG release into a jejunal vein. Very small doses of glucagon administered intraportally during hyperglycemia were effective in promoting IRI release.

It is concluded that a fall in blood glucose from the basal state is a stimulus, and hyperglycemia is an inhibitor, of pancreatic IRG release. It is possible that glucagon may act in the basal state to deliver repeated small pulses of glucose and insulin into the circulation.
Hyperglycemia and Inhibition of Insulin Secretion during Administration of Diazoxide and Trichlormethiazide in Man
Authors: Seltzer Holbrooke S , Allen E William
Published: December 2014

Reversible “diabetes” was produced in eight normal male subjects by administering between 400 mg. and 645 mg. of diazoxide and 8 mg. of trichlormethiazide per day for four to seven days. Insulin secretory responses to oral and intravenous glucose loads were determined on the last treatment day and the following morning, respectively. Four to six weeks later both tests were repeated to obtain control data.

The speed of breakdown in glucose tolerance was proportional to daily diazoxide dosage, which in turn was limited by the severity of side effects. Carbohydrate turnover tended to worsen each day, even after correction of severe symptomatic hypokalemia in two subjects. The induced “diabetic” state was associated with sluggish insulin release as blood glucose rose, and with greatly decreased hormonal output per unit of glycemic stimulus—the same two secretory defects which characterize the clinical onset of hereditary diabetes mellitus.

The dala suggest that the potent diabetogenicity of diazoxide given with trichlormethiazide may be almost entirely due io blockade of insulin release, either by direct action or by stimulating alpha adrenergic receptor sites in the beta cell. The synergistic effect of natriuretic analogues like trichlormethiazide probably reflects superimposed potassium deficiency, evidence of which consistently underlies the weaker hyperglycemic property of diuretic benzothiadiazines but is not caused by diazoxide itself. Thus, “diazoxide diabetes” appears to be functionally distinct from ordinary “thiazide diabetes” and, in fact, closely resembles spontaneous diabetes mellitus clinically. Since the condition can be predictably induced and is entirely reversible, it may provide a useful experimental model for further study of the inherited disease in man.
Antagonism Between the Effects of Insulin and Glucagon on the Isolated Liver
Authors: Mackrell Dennis J , Sokal Joseph E
Published: December 2014

Antagonism was demonstrated between the effects of insulin and glucagon, added simultaneously to the perfusing blood, on phosphorylase activity, glucose output and urea production of the isolated rat liver. However, the degree of antagonism varied greatly, according to the action under study, and there appeared to be a clear-cut hierarchy in the effects of each hormone. For glucagon, this was (stimulation of): (1) phosphorylase activity, (2) glycogenolysis and glucose release, (3) urea production. For insulin, it was (inhibition of): (1) urea production, (2) glycogenolysis, (3) phosphorylase activation. Thus, high concentrations of insulin completely failed to inhibit the phosphorylase activation induced by 1.4 mμg./ml. of glucagon, while modest concentrations of insulin totally suppressed the stimulation of urea production induced by sustained glucagon concentrations at least ten times greater, and well above the biologic range. Our findings argue against a single common primary site of action of these two hormones.
Immunoreactive Insulin, Glucose Tolerance, and Carbohydrate Inducibility in Types II, III, IV, and V Hyperlipoproteinemia
Authors: Glueck Charles J , Levy Robert I , Fredrickson Donald S
Published: December 2014

The elevation of plasma glycerides by a high carbohydrate diet (carbohydrate induction) has been systematically correlated with glucose tolerance, insulin output and ponderal index in normals and in patients with different types of hyperlipoproteinemia. Carbohydrate inducibility (ΔTG) was similar in normals and patients with Type II hyperlipoproteinemia. Delta TG was nearly always much greater than normal in Type III, and was quite heterogeneous in type IV. The scatter in ΔTG values in Type V patients was extremely great. The basal triglyceride and ΔTG were positively correlated only in Type IV.

Abnormal glucose tolerance was present in approximately one third of Types II and III, one half of Type IV and 80 per cent of Type V patients.

Hyperinsulinemia was present in most Type V patients, while a majority of Type II and III patients had relatively normal insulin levels. Approximately one third each of the Type IV patients had low, normal, and abnormally high insulin levels. Increasing insulin and insulinogenic indices were correlated with increased ATG in the normal, but not in any of the patient groups. In the specific groups of hyperglyceridemic patients in this study, plasma insulin levels did not appear to be a primary determinant of the degree of carbohydrate induction.
Diabetic Ketosis: Elevated Serum Glutamic-Oxaloacetic Transaminase (SGOT) and Other Findings Determined by Multi-channel Chemical Analysis
Authors: Cryer Philip E , Daughaday William H
Published: December 2014

Twelve-channel chemical analysis (sodium, potassium, chloride, CO2, total protein, albumin, calcium, alkaline phosphatase, total bilirubin, urea nitrogen, glucose, and glutamicoxaloacetic transaminase [SGOT] was performed on sera from fifty-five of sixty-one cases of diabetic ketosis hospitalized over a two-year period. The cases represented consecutive admissions and were not selected for severe ketoacidosis. Abnormalities of the serum sodium, potassium, chloride, CO2, calcium, urea nitrogen and glucose generally conformed to recognized patterns, and abnormalities of the total protein, albumin, alkaline phosphatase, and total bilirubin were noted in a minority of cases. In contrast, the SGOT was elevated in 69 per cent of all cases and in 82 per cent of those in whom the determination was performed on the day of admission. Elevation of the SGOT in ten of eleven patients with hepatomegaly and the relationship between elevations of the SGOT and elevations of the serum glutamic-pyruvic transaminase and lactic dehydrogenase, as well as the recognized occurrence of fatty infiltration of the liver in uncontrolled diabetes, are consistent with an hepatic origin for the elevated SGOT found in patients with diabetic ketosis.
The Role of Cyclic AMP in the Control of Carbohydrate Metabolism
Authors: Sutherland Earl W , Robison G Alan
Published: December 2014

Cyclic AMP plays an important role in the regulation of metabolism generally. Emphasis in the present review has been placed on carbohydrate metabolism, but lipid metabolism has also been discussed to some extent. The chief role of cyclic AMP in several tissues seems to be to facilitate or promote the mobilization of glucose and fatty acid reserves. In the liver, glucagon and the catecholamines cause an increase in the intracellular level of cyclic AMPby stimulating adenyl cyclase. This increase in the level of .cyclic AMP leads to a net increase in hepatic glucose production by at least three mechanisms: stimulation of phosphorylase activation, suppression of glycogen synthetase activity, and stimulation of gluconeogenesis. The catecholamines also stimulate adenyl cyclase in muscle and adipose tissue. Among the principal effects of cyclic AMP in these tissues are glycogenolysis in muscle and lipolysis in adipose tissue.

Another role of cyclic AMP is to enhance or promote the release of insulin from pancreatic beta cells. Insulin then travels to the liver and adipose tissue to suppress the accumulation of cyclic AMP, and may also antagonize the action of cyclic AMP in muscle. Cyclic AMP is thus seen to mediate the actions of several catabolic hormones as well as promote the release of an anabolic hormone which acts in part by opposing cyclic AMP.

Since cyclic AMP is involved in the release as well as several of the actions of insulin, the possible role of cyclic AMP in diabetes has been discussed. Human diabetes mellitus is recognized as the result of a basic genetic defect, the nature of which is undefined. One line of evidence implicates basement membrane thickening as an early event in the patho genesis of diabetes. Further study of the formation and breakdown of the basement membrane may therefore lead to a better understanding of the genetic defect. Whether or not cyclic AMP plays a regulatory role in basement membrane synthesis is presently unknown.

Another defect recognizable in prediabetics is faulty insulin release in response to glucose infusion. This could be secondary to basement membrane thickening, but there is also evidence that the cyclic AMP mechanism may be defective. At another level, the role of cyclic AMP is more obvious: insulin deficiency leaves unopposed the actions of hormones which stimulate the production of cyclic AMP, thereby contributing to the glucose plethora and ketosis so often seen in the later stages of the disease.
Failure of Insulin Therapy to Prevent Cardiovascular Lesions in Diabetic Rats Fed an Atherogenic Diet
Authors: Wilson Robert B , Martin Julio M , Hartroft W Stanley
Published: December 2014

In previous experiments, partially depancreatized diabetic rats, fed an atherogenic diet, consistently developed higher levels of serum cholesterol and more numerous and severe cardiovascular lesions than did similarly fed non-diabetic animals.

In the present experiment, insulin therapy prevented glucosuria from 80 to 95 per cent of the time in a group of diabetic rats fed an atherogenic diet. This therapeutic regimen was effective in promoting weight gain, improving food utilization, preventing ketonuria and, except during the first two weeks, in restricting the concentrations of serum cholesterol to within the same range as those of raline-treated nondiabetics. But this restriction in concentrations of serum cholesterol in the treated diabetics did not decrease the incidence or severity of their vascular lesions, as occurred when a comparable reduction of hyper-cholesterolemia had been effected by dietary methods.

Moreover, within groups, individual concentrations of serum cholesterol bore no relation to the severity of vascular lesions. We conclude that in this model, factors other than concentration of serum cholesterol must be important in the pathogenesis of vascular lesions.
Inhibition of Insulin Secretion by Aryl-substituted Secondary Aminoethanols
Authors: Bressler Rubin , Vargas-Cordon Mario , Brendel Klaus
Published: December 2014

The administration of glucose, tolbutamide, ACTH, and glucagon to mice resulted in increase of plasma insulin levels. These increases were all inhibited by the prior administration of aryl-substituted secondary aminoethanols (ASAE). Cyclic 3′,5′ AMP resulted in increased levels of plasma insulin in intact mice, and this stimulatory effect was also inhibited by the aryl-substituted secondary aminoethanols. The locus of the inhibitory effect of these compounds on insulin secretion is discussed.
Steady State Plasma Insulin Response to Continuous Glucose Infusion in Normal and Diabetic Subjects
Authors: Reaven Gerald M , Farquhar John W , Nakanishi Richard H
Published: December 2014

Normal subjects and diabetic patients with various degrees of hyperglycemia were given continuous intravenous glucose infusions for three hours in order to achieve constant plasma levels of glucose and immunoreactive insulin. During the last ninety minutes of this infusion period, at which time steady state conditions were observed, blood was obtained for measurement of plasma glucose and immunoreactive insulin concentration. Absolute levels of plasma insulin produced by the stimulus of the glucose infusions were extremely variable from patient to patient and were relatively independent of the degree of hyperglycemia. Patients with diabetes did not have lower steady state plasma insulin concentrations as a group, and this was true whether the insulin response was considered in absolute or relative terms. It is concluded that significant differences do exist in individual sensitivity to endogenous insulin, and that hyperglycemia in patients with maturity onset diabetes is not simply a function of lack of insulin.
Actions of Insulin and Growth Hormone on Collagen and Chondroitin Sulfate Synthesis in Bone Organ Cultures
Authors: Wettenhall R E H , Schwartz P L , Bornstein J
Published: December 2014

1. The effects of insulin and growth hormone have been studied on collagen and chondroitin sulfate synthesis in bones growing in a steady state achieved by a continuous-flow bone culture system.

2. It is seen that insulin, but not growth hormone, has a significant effect on the synthesis of collagen and a marginal effect on the synthesis of chondroitin sulfate.

3. The significance of these findings is discussed.
Possible Role of Hydrazine Group in Hypoglycemia Associated with the Use of Certain Monoamine-oxidase Inhibitors (MAOI's)
Authors: Potter William Z , Zaharko Daniel S , Beck Lyle V
Published: December 2014

It has been reported that some patients treated chronically with certain monoamine-oxidase inhibitors (MAOI's) exhibit as a complication hypoglycemia, or potentiation of insulin or sulfonylurea induced hypoglycemia. This effect has been attributed to interference by the MAOI with the hyperglycemic role of the sympathoadrenal system in glucose homeostasis, possibly through replacement of endogenous stored catecholamines by impotent “false transmitter.” These hypotheses lead to certain expectations, none of which were realized in the present experiments. Instead, evidence was obtained that it is the hydrazine group present in certain MAOI's, rather than their MAOI activity, to which hypoglycemic action should be attributed. Hydrazine and the hydrazine MAOI, phenelzine, induced similar decreases in plasma glucose and insulin levels of overnight fasted rats; phenelzine induced increases in plasma FFA levels. The nonhydrazine MAOI, pargyline, induced marked increases in plasma glucose levels.
Resistance of Rabbits and Guinea Pigs to the Diabetogenic Effect of Streptozotocin
Authors: Kushner B , Lazar M , Furman M , Lieberman T W , Leopold I H
Published: December 2014

Streptozotocin is an antibiotic with antitumor properties. It has been reported to be diabetogenic in dogs, monkeys, hamsters, rats, and mice. Rabbits and guinea pigs were found to be resistant to the diabetogenic action of streptozotocin. Resistance in these species was not related to impaired ability to maintain adequate serum concentrations of the drug. Streptozotocin incubated with rabbit serum and liver homogenate maintained its diabelogenic properties when injected in the rat. Liver and pancreas homogenates of the resistant species did not metabolize the drug in vitro as determined spectrophotometrically. It is postulated that the diabetogenic action of streptozotocin may be related to its ability to impair NAD synthesis. It is postulated that the drug apparently blocks the synthesis of NAD from nicotinamide but has no effect on the synthesis of NAD from nicotinic acid, the pathway which may be preferentially employed by rabbits and guinea pigs.
“Instant” Blood Sugar Measurement Using Dextrostix and a Reflectance Meter
Authors: Jarrett R J , Keen H , Hardwick C
Published: December 2014

A new “reflectance meter,” capable of reading and quan-titating the color change of the Dextrostix blood-glucose oestimation, has been tested using capillary blood samples from patients attending a diabetic clinic and men having diagnostic glucose tolerance tests. The correlation of these blood glucose results with those obtained with an Auto-Analyzer method was very high (r = 0.98) and replication by the reflectance meter method was also satisfactory.
Plasma Amino Acid Levels in Diabetic Ketoacidosis
Authors: Felig Philip , Marliss Errol , Ohman John L , Cahill George F
Published: December 2014

The plasma concentration of nineteen amino acids was examined in patients with diabetic ketoacidosis prior to institution of treatment and in healthy controls. A two to three-fold increase in plasma leucine, isoleucine, valine and α-amino butyrate was observed in the diabetics. In contrast a 25 to 40 per cent reduction was noted for the key glycogenic amino acids alanine, glycine, threonine and serine. It is concluded that in the absence of adequate insulin, increased peripheral mobilization of ketogenic amino acids and enhanced hepatic extraction of glycogenic amino acids contribute to the development of the acute diabetic syndrome.
Diabetic Ketosis: Interpretation of Elevated Serum Glutamic-oxaloacetic Transaminase (SGOT) by Multi-channel Chemical Analysis
Authors: Chen Jeffrey C , Marsters Roger , Wieland Ralph G
Published: December 2014

Multi-channel determination of serum glutamic-oxaloacetic transaminase (SGOT) frequently reveals an elevation in patients with diabetic ketoacidosis. This elevation may represent acetoacetate in the serum and thus be an artifact. It is therefore necessary to include the determination of a serum blank or to utilize a different technic to measure the SGOT in patients with ketonemia.
Diabetes in a Pair of Identical Twins
Authors: Malins J M , Cassar J , Pyke D A
Published: December 2014

We report an unusual pair of identical twins.

Jennifer B. developed diabetes at the age of four and has been on insulin ever since. She is now aged thirty and has several complications of the disease.

Shireen B., her twin, was found, immediately after appendectomy at the age of eight, to have glycosuria, and glucose tolerance was highly abnormal. She was put on insulin, but soon ceased toneed it and another glucose tolerance test after fifteen days was normal. Twenty-two years later, when thirty-seven weeks pregnant, and three and six months postpartum, she was tested again, withglucose tolerance test and insulin assay. The glucose tolerance tests were normal; the insulin response was slightly abnormal.

These findings together with those in a larger series of twins do not tend to suggest that diabetes will develop in all identical twins of diabetics.
Response of Beta Cells to Different Levels of Glucose: Fetal Pancreases Grown in Organ Culture and Subsequently Transplanted to Maternal Hosts
Authors: Hegre Orion D , Wells Lemen J , Lazarow Arnold
Published: December 2014

Portions of pancreases from fetal rats (normal or alloxan diabetic mothers) of 19.5 days were grown in organ culture for four days on either a low glucose medium (162 to 170 mg. glucose per 100 ml.) or a high glucose medium (1,031 to 1,073 mg. glucose per 100 ml.).

Certain cultures were fixed for microscopic study. Other cultures were transplanted to the mothers at two sites: into the anterior chamber of the eye and under the capsule of the kidney. Four or ten days later, the grafts were removed, fixed and prepared for microscopic study.

Pancreases of fetuses from normal mothers had granulated beta cells at the time of explantation. When explants were grown on the high glucose medium, the beta cells became degranulated—the insulin stored at the time of explant was released from the beta cells. Subsequent transplantation of such cultures into the normal mothers restored the beta cell granulation, i.e., new insulin was synthesized and stored within the beta cells.

Pancreases of fetuses from alloxanized diabetic mothers had de granulated beta cells at the time of explantation. When these explants were grown on the low glucose medium, the beta cells developed extensive granulation representing a synthesis and storage of insulin.

Following subsequent transplantation of such cultures into the diabetic mothers, the beta cells became degranulated, i.e., release of stored insulin from the beta cells.

These observations indicate that the beta cells maintain their functional integrity (ability to store or release insulin in response to glucose) both in organ culture and when subsequently grown as grafts in maternal hosts.