bluuebunny/crossref_metadata_2025 huggingface dataset:
Lactate Turnover and Gluconeogenesis in Normal and Obese Humans: Effect of Starvation
Authors: Kreisberg R A , Pennington L F , Boshell B R
Published: December 2014

Turnover rates of lactate and glucose were determined in normal, obese, and fasted obese human subjects. L—(+) lactate-U-C-14 (50μc.) and glucose-l-C-14 (50 μc.) were administered over a four-hour period on consecutive days by a primed-infusion technic. Lactate and glucose interconversion rates were calculated from precursor-product specific activity ratios obtained during the infusion period and the rates of lactate and glucose turnover. Glucose turnover, oxidation, recycling, and conversion to lactate, when expressed on a mg./kg./hr. basis, were significantly less in obese subjects than in normals; however, when expressed as a percentage of the turnover, no significant differences were observed. Glucose oxidation represented 14 per cent; recycling, 10 per cent; and conversion to lactate, 66 per cent of the glucose turnover rate. Approximately 15 per cent of the glucose turnover was derived from lactate. In contrast, there were no significant quantitative or qualitative differences in the metabolism of lactate by normal or obese subjects. Lactate oxidation represented 11 per cent and lactate conversion to glucose 21 per cent of the lactate turnover rate. During starvation, there was a 30 per cent reduction in glucose pool size, turnover, and oxidation. Blood lactate concentrations and lactate turnover were unchanged despite decreased conversion of glucose to lactate. The conversion of lactate to glucose increased from 14 ± 2 to 21 ± 2 mg./kg./hr. and represented 36 per cent of the lactate turnover. The fraction of the glucose turnover derived from lactate increased two-fold, from 17 to 38 per cent. These results are in general agreement with those obtained in animals and are the first quantitative estimates of lactate-glucose interconversion rates in man. The combination of decreased glucose conversion to lactate and increased lactate conversion to glucose in the presence of an unchanged blood lactate concentration and turnover requires that there be increased synthesis of lactate from sources other than glucose. In addition, increased conversion of lactate to glucose at unchanged blood concentrations indicates enhanced extraction of lactate during starvation.
Diabetes Mellitus and Pernicious Anemia
Authors: Munichoodappa C , Kozak George P
Published: December 2014

From 1959 to 1968, thirty-six cases of pernicious anemia (PA) were noted in 11,144 patients with diabetes mellitus (DM) at the Joslin Clinic (incidence 3.2/1,000). Of the thirty-six, only one was not insulin dependent. The female to male ratio was 7:5. Age ranged from thirty-four to eighty-one years. In twenty-eight patients with DM, a mean period of 12.6 years elapsed from time of diagnosis of diabetes mellitus to development of PA. In eight, PA preceded DM by a mean period of 6.6 years. Vitamin B12 deficiency neuropathy was present in nine patients and in only six of these was there clinically recognizable anemia. Hypothyroidism was present in two patients.

Histochemical and immune abnormalities common to both disorders are reviewed and possible causes for association are discussed.
A Method for the Isolation of Insulin from Single Human Pancreas
Authors: Shapcott Dennis , O'Brien Donough
Published: December 2014

A method is described for the isolation of insulin from single human pancreas specimens involving a traditional acid-ethanol extraction, followed by gel filtration and isoelectric focusing.
Effect of Theophylline, Glucagon and Theophylline plus Glucagon on Insulin Secretion in the Premature Infant
Authors: Grasso S , Messina A , Saporito N , Reitano G
Published: December 2014

Serum insulin was measured in thirty premature infants in the first twenty-four hours of life following the administration of theophylline, glucagon, or theophylline plus glucagon. Theophylline (1 mg. per min.) produced a striking rise in serum insulin without change in blood glucose. Neither glucagon (0.4 γ per min.) nor theophylline (0.5 mg. per min.) produced any significant change in the levels of blood glucose and serum insulin. However, the simultaneous administration of these doses of glucagon and theophylline was followed by a progressive rise in blood glucose and serum insulin. The insulin secretion with this combination exceeded that seen with a rapid injection of 300 γ of glucagon.
Plasma Insulin and Glucose Responses of Healthy Subjects to Varying Glucose Loads During Three-hour Oral Glucose Tolerance Tests
Authors: Castro Albert , Scott James P , Grettie Donald P , Macfarlane Dorothy , Bailey Richard E
Published: December 2014

The plasma glucose and plasma immunoreactive insulin concentrations of twelve healthy, nonobese, adult subjects were compared following administration of oral glucose loads of 50, 75 and 100 gm., and 1.75 gm./kg. body weight. The time of occurrence and the magnitude of maximal plasma glucose and insulin concentrations were unaffected by the 25 gm. increases in glucose load. The 50 gm. glucose load gave the smallest plasma glucose response during the three-hour tests and this response was statistically distinguishable from the plasma glucose responses due to the 100 gm. and 1.75 gm./kg. loads (p < 0.05). The plasma glucose responses due to the other loads did not differ from each other. Insulin responses, estimated by either summing allthe plasma insulin values or by measuring the areas under the curves, increased approximately 35 per cent with the first 25 gm. glucose load increment (50 to 75 gm.) and 27 per cent with the second 25 gm. load increment (75 to 100 gm.) during the three-hour study. The differences in insulinresponses between the 50 gm. load and the 100 gm. or 1.75 gm./kg. loads were highly significant (p < 0.01) while the difference between the insulin responses following the 75 gm. and 1.75 gm./kg. loads had lower significance (p < 0.05). Differences in insulin responses of the other loads were not significant. Increases in glucose loads above 120 gm. did not further increase the insulin response. This provides evidence that maximal insulin responses provoked by an oral glycemic stimulus alone in subjects are achieved with 100 gm. A wide range was observed in the plasma insulin concentrations among these healthy individuals for any given load, at any one time, and was probably due to biological variation.

The fact that incremental changes in glucose load particularly influenced plasma glucose and insulin concentrations relatively late in the glucose tolerance tests, and that mean insulin peakconcentrations did not differ, indicates that increasing glucose load results in a more prolongedinsulinogenic stimulus rather than the acute release of greater quantities of insulin relatively abruptly. These studies provide evidence that the response associated with increasing glucose load is to some extent a function of the quantity of glucose ingested, and that the significant increases in insulin response commonly occur in association with concurrent alterations in plasma glucose concentrations. The results also indicate that the 50 gm. glucose load results in a different plasma glucose response than does the 100 gm. and 1.75 gm./kg. loads and consequently requires different criteria for interpretation of glucose tolerance testing.
Diagnosis of Diabetes: The Size and Nature of Carbohydrate Load
Authors: Chandalia Hemraj B , Boshell Buris R
Published: December 2014

The blood sugar (eighteen subjects) and serum insulin levels (sixteen subjects) following the administration of 30 gm. glucose and 45 gm. glucose per square meter of body surface area were compared. In the patients studied, the larger glucose load resulted in significantly greater blood glucose responses (area under the curve, two-hour blood glucose, three-hour blood glucose) and increased sensitivity of the test. The areas under the glucose and insulin curves with the two different glucose loads had a linear relationship, thereby providing some basis for the comparison of data obtained by the use of different amounts of glucose administered on the basis of the body surface area.

The blood glucose levels following the administration of seven ounces of Glucola (75 gm. carbohydrate solution) were compared with those following the administration of (1) 100 gm. glucose in twenty-seven subjects and (2) 1.75gm. glucose/kg, of ideal body weight in twelve subjects. Although the interpretation of the individual glucose tolerance tests changed in twelve subjects, the areas under the glucose tolerance curves and summed glucose values were not significantly different whether Glucola or the two glucose loads were used thus demonstrating similarity of the Glucola and the glucose loads.
Progressive Gangrene of an Extremity Due to Mucormycosis in a Diabetic Patient
Authors: Palmer Darwin L , Weitzner Stanley , Simpson John C F
Published: December 2014

The first reported case, except for a burn wound, of mucormycosis producing a progressive gangrene in an extremity is described. Diagnostic criteria, etiologic considerations and therapy are discussed. Since currently available therapy may be effective, the necessity of making an early diagnosis of mucormycotic infection, even though in an unusual location, is emphasized.
Beta Cell Secretion—from the Standpoint of a Pathobiologist
Authors: Lacy Paul E
Published: December 2014

A proposed model depicting the biologic events in the formation, storage and releaseof insulin in beta cells is presented. The proposed sequence of events is as follows: intracellular glucose metabolism signals the initiation of proinsulin synthesis in the endoplasmic reticulum; pro-insulin is transferred to the Golgi complex; the conversion of proinsulin to insulin probably occurs in the Golgi complex and intermediate beta granules may be present in this structure; mature beta granules enclosed in smooth membranous sacs are released into the cytoplasm and becomeattached to the microtubular-microfilament system; glucose metabolism initiates the entry of calcium which triggers the change in physical conformation of the microtubules with resultant displacement of the granules to the cell surface where they are released by emiocytosis.
Diabetic Hemorrhagic Glaucoma
Authors: Hohl R D , Barnett D M
Published: December 2014

Diabetic hemorrhagic glaucoma was seen in forty inpatients of the Joslin Clinic in the ten-year period ending 1964. Twenty patients were juvenile-onset and twenty were maturity-onset diabetics. The average duration of diabetes was 20.8 years for both groups. Pain and blindness were the most common presenting symptoms. Rubeosis iridis and extensive proliferative diabetic retinopathy were seen in every glaucomatous eye. Other evidence of angiopathy (nephropathy, neuropathy, and peripheral vascular impairment) coexisted in many of the patients.

A study of these patients indicates that (a) diabetic hemorrhagic glaucoma is most often seenin association with proliferative diabetic retinopathy, and (b) its development portends a serious loss of useful vision. Pertinent microscopic, histochemical, and experimental observations are cited to support the view that impaired ocular blood flow with resulting retinal hypoxia is a common feature of this disorder, disposing the diabetic iris to the development of rubeosis and subsequent anterior chamber hemorrhage leading to glaucoma.
Synergistic Effect of Essential Amino Acids and Glucose upon Insulin Secretion in Man
Authors: Floyd John C , Fajans Stefan S , Pek Sumer , Thiffault Charles A , Knopf Ralph F , Conn Jerome W
Published: December 2014

Arginine, leucine, or histidine, and glucose were each administered intravenously, in 30-gm. amounts on separate occasions to the same healthy subjects. Each of the amino acids and glucose in these same amounts were administered also as mixtures. Synergism in the stimulation of the release of insulin was demonstrated when the sum of the increases in plasma insulin which resulted from the separate administrations of an amino acid and glucose was exceeded by that obtained when they were administered as a mixture. A synergistic effect was exerted by each of the three amino acid-glucose combinations; it was greatest with arginine and glucose and least with histidine and glucose. Synergism probably results from the effects of these stimuli upon the pancreatic beta cell; it is not dependent upon humoral gastrointestinal factors released after the ingestion of these nutrients.
Effects of Intravenous and Oral Infusion of Monosaccharides on Serum Insulin Levels in Rabbits
Authors: Nijjar MS , Perry WF
Published: December 2014

The same dose of glucose given intravenously or orally produced a similar increase in serum insulin, although the blood glucose level was much lower after oral administration than after intravenous administration. These findings support the hypothesis that an additional insulinotropic mechanism other than hyperglycemia is associated with the oral administration of glucose. The specificity of this mechanism was investigated by examining the insulin response following oral and intravenous infusions of various monosaccharides other than glucose, e.g., mannose, fructose, galactose, α-methyl glucoside, ribose and xylose. Oral infusion of these monosaccharides, except mannose and fructose, produced a progressive rise in the blood level of the monosaccharides. All monosaccharides examined except α-methyl glucoside led to an increase in serum insulinlevel when given intravenously. However, after oral administration only glucose, galactose and xylose led to an increase in serum insulin, whereas mannose, fructose and ribose had no effect. These findings suggest that the proposed insulinotropic mechanism elicited by oral administration is not specific to glucose but does require an increase in the blood saccharide level after oral administration. However, oral infusion of the sugar analogue, α-methyl glucoside, did not promote insulin secretion despite rapid absorption and marked increase in its level in the blood. This suggests that a sugar, in addition to being absorbed with subsequent increase in blood level, must possess an active reducing group for the elicitation of insulin release.

The intravenous infusion of readily metabolizable sugar (glucose, mannose and fructose) produced marked insulin response whereas similar infusion of xylose, ribose, and galactose elicited only a moderate insulin response. The intravenous injection of a nonmetabolizable sugar, α-methyl glucoside, had no stimulatory effect. These findings suggest that the rise in blood saccharidelevel per se after intravenous administration may not be the sole stimulus for insulin secretion but possibly a metabolite of the infused sugar is a stimulus. This inference was supported by the finding that the intravenous injection of pyruvate enhanced the secretion of insulin.
Acid Mucopolysaccharide Changes in Diabetic Kidneys
Authors: Berenson Gerald S , Ruiz Harold , Dalferes Edward R , Dugan Fortune A , Radhakrishnamurthy Bhandaru
Published: December 2014

Studies were conducted on the mucopolysaccharide (MPS) composition of kidneys from seventeen diabetic patients and from six control individuals presumably without renal disease. Thekidney tissues were divided by gross dissection into cortical and medullary portions, and the MPSwere isolated and quantitated from these sections. The contents of hyaluronic acid, heparitin sulfate, and chondroitin sulfates were compared to the clinical and pathological observations on thepatients. According to the MPS pattern of heparitin sulfate and hyaluronic acid, the diabetic kidneys were divided into three groups. Heparitin sulfate was increased fairly consistently in most of the diabetic samples, and was particularly increased in one group with clinically severe diabetes showing the nodular diabetic (Kimmelstiel-Wilson) lesion. Seven of the samples demonstrated a MPS composition somewhat similar to controls, and these were observed to have fewer abnormal changes histologically. A third group showed an increase of hyalufonic acid, and in these kidneys diffuse glomerulosclerosis was the most consistent glomerular lesion.

The observations suggest that the two types of specific glomerular lesions found in diabetic kidneys have different cellular origins. The increased heparitin sulfate suggests a relationship of renal changes in diabetes to a vascular origin. A rather interesting similarity of MPS changeshas been observed in amyloidosis and in intima sections of the aorta with atherosclerosis.
Over-all Therapeutic Usefulness of Glybenclamide, a New Hypoglycemic Sulfonylurea
Authors: Rull Juan A , Gonzalez-Millan Heliodoro , Quibrera Ricardo , Garcia-Viveros Mariano , Lozano-Castaneda Oscar
Published: December 2014

The over-all therapeutic usefulness of glybenclamide, a new derivative of the hypoglycemie sulfonylureas, was studied in 116 diabetics of all types.

Glybenclamide appears to be a very potent hypoglycemie drug without serious toxicity on short-term trial but its clinical spectrum is similar to that of previously known hypoglycemie sulfonamides.
Portal and Peripheral Vein Immunoreactive Insulin Concentrations Before and After Glucose Infusion
Authors: Blackard William G , Nelson Norman C
Published: December 2014

Catheterization of the portal vein via the umbilical vein was performed under local anesthesia in twelve nondiabetic subjects prior to exploratory laporatomy for a variety of conditions. Immunoreactive insulin (IRI) in simultaneously obtained portal and peripheral vein plasma was determined before, during, and after a two-minute glucose infusion (25 gm.). Two phases of insulin secretion were apparent from portal vein IRI concentrations. A rapid secretory phase beginning one minute after start of the infusion and lasting three to four minutes was followed by a slower secretory phase beginning approximately ten minutes after start of the glucose infusion. The absolute amount of “big” insulin (proinsulin-like material) in the portal vein was similar during the first phase and the early part of the second phase of insulin secretion. A significant positive correlation between portal vein and peripheral vein IRI responses to glucose was noted.
Variations in Response to Severe Alloxan Diabetes in Arteriosclerotic and Nonarteriosclerotic Rats
Authors: Wexler Bernard C , Saroff Jack , Judd Joseph
Published: December 2014

Repeatedly-bred rats develop arteriosclerosis, hyperlipidemia, hyperglycemia and other degenerative changes, spontaneously. An injection of alloxan (10 mg./100 gm. body weight, subcutaneously, eighteen-hours postfasting) given to healthy, virgin and to arteriosclerotic and diabetic breeder rats caused severe ketosis, hyperglycemia, hyperlipidemia and fatty metamorphosis of the liver. Animals were sacrificed daily for one week and after the fourth and eighth week of severe, untreated diabetes.

The previously arteriosclerotic rats showed the greater catabolic and pathophysiologic changes. Many animals died on the third day postalloxan with massive fatty metamorphosis of the liver. At this time, adrenal and thymus gland weights, serum enzymes, e.g., SGOT, SGPT and LDH, serum lipids, e.g., free fatty acids, triglycerides and cholesterol, serum corticosterone and urinary 17-ketosteroids, as well as chemical analyses of hepatic lipids, e.g., total lipids, trigly- ceride and cholesterol, all reflected the severe insulin deficiency.

Eventually, the severity of these pathophysiologic changes subsided. Approximately half of the animals became emaciated with milky serum containing high levels of glucose and lipids. These animals were ketotic, their beta cells were agranular and they were severely arteriosclerotic. Remaining animals were “obese,” with fatty livers but normal-appearing serum containing less glucose and lipid than their emaciated counterparts. These “obese” diabetic rats had less severe ketosis, partially degranulated beta cells and regression of their arteriosclerosis. This dichotomous response to severe diabetes may be due to the partial recovery of beta cells of some animals concomitant with partial correction of defective lipid and carbohydrate metabolism.
Long-term Effects of Transsphenoidal Hypophysectomy on Growth Hormone, Renal Function and Eyeground in Patients With Diabetic Retinopathy
Authors: Teuscher Arthur , Escher Franz , König Heinrich , Zahnd Gaston
Published: December 2014

Pituitary ablation was used to treat diabetic retinopathy in twelve patients. The treatment was associated with stabilization and lack of progression of visual findings in seven patients for thirty to ninety-nine months following surgery with loss of growth hormone responsiveness in three, lowering of fasting growth hormone levels in three and lowering of growth hormone reserve in one. Renal function (glomerular filtration rate and renal plasma flow) was reduced by 30 to 37 per cent within four months following surgery in those patients who showed loss of growth hormone activity. Reduced function was ameliorated with human growth hormone. Renal clearance studies indicate that loss of growth hormone may lead to increased renal arterial resistance. A beneficial effect on renal function was not observed in later observation periods. The decreased insulin requirement and increased morbidity in the posthypophysectomy state seem to be related to the loss of growth hormone.
Diabetic Ketosis: Serial Plasma Growth Hormone Concentrations During Therapy
Authors: Cryer Philip E , Daughaday William H
Published: December 2014

Plasma growth hormone (GH) concentrations were measured serially during therapy in twelve cases of diabetic ketosis. The initial plasma GH levels varied widely, ranging from 2 to 215 ng./ml., and were not related to the clinical severity of the ketosis, the degree of depression of the serum bicarbonate, or the magnitude or the hyperglycemia. An increase in the plasma GH concentration followed the institution of insulin therapy in ten of twelve cases. This rise was associated with a fall in the plasma glucose concentration though the latter reached hypoglycemic levels in only one instance. There was no relationship between the total insulin administered during the first twelve hours of therapy and the area under the GH curve for the same period or the initial or peak plasma GH concentration. Thus, despite its known diabetogenic effect and the frequent occurrence of elevated plasma concentrations in ketotic diabetics, growth hormone cannot be a constant major determinant of the insulin resistance of diabetic ketosis.
Characterization of Glucagon-like Immunoreactivity (GLI)
Authors: Valverde Isabel , Rigopoulou Demetra , Marco Jose , Faloona Gerald R , linger Roger H
Published: December 2014

The present studies were designed to obtain further information concerning the chemical interrelationships of the fractions of glucagon-like immunoreactivity (GLI) present in gastrointestinal tissues, their biologic activity, and their immunochemical and electrophoretic properties. Chromatography of canine jejunal extracts on a Bio-Gel P-10 column separated GLI into two fractions; one, designated Peak II, eluted with the glucagon-I-131 marker (molecular weight 3,500), while the other, designated Peak I, appeared before the insulin-I-131 marker (molecular weight >6,000). Neither rechromatography, nor incubation in 8 M urea, acetic acid, or mercaptoethanol changed the elution volume of Peak I; however, trypsin caused a major loss of immunoreactivity and a shift of residual immunoreactivity to the postglucagon-I-131 zone.

Peak I was devoid of glycogenolytic activity in the perfusedrat liver, as was its tryptic product, while Peak II was consistently as active as pancreatic glucagon. Immunoprecipitated Peak II was also active, proving that the immunoreactive fraction was responsible for its biologic action.

Unlike pancreatic glucagon, Peak I, Peak II, and the tryptic product of Peak I diluted disproportionately with the less specific antiserum; however, Peak II could not be differentiated from pancreatic glucagon by means of polyacrylamide gel disc electrophoresis.

It is concluded that (1) Peak I does not consist of Peak II bound noncovalently either to itself or to another protein; (2) Peak I and its tryptic product are devoid of glycogenolytic activity while Peak II has the approximate activity of pancreatic glucagon; (3) the glycogenolytic and immunoreactive components in the eluate containing Peak II are probably on the same molecule; (4) both Peak I, its tryptic product, and Peak II are immunologically different from pancreatic glucagon.
Standardization of Terminology in Diabetes: Types and Family Histories
Authors: Baumslag Naomi , Yodaiken Ralph E , Varady John C
Published: December 2014

A questionnaire was sent out to a number of investigators working in clinical diabetes mellitus. The response confirmed the impression gained from the literature that uncertainty exists with regard to the use of the term “juvenile diabetes” and confusion as to the meaning of “blood relatives” and consequently “a positive family history.” On the basis of the replies obtained and from a review of the literature, an approach to standard classification is suggested which would include all known types of diabetes and provide a mechanism for comparing different diabetic groups.
Comparative Study of Diabetes Knowledge Among Juvenile Diabetics and Their Parents
Authors: Collier Boy N , Etzwiler Donnell D
Published: December 2014

One hundred and twenty-nine children with diabetes from fifty-eight junior and senior high schools in the Minneapolis- St. Paul area and their parents were given a thirty-four-item test to evaluate their knowledge of diabetes and to determine if there were significant differences in understanding. Areas of deficiency were noted particularly involving understanding of diet, acidosis and alterations in management that occur with changes in activity or illness.

Descriptive material is presented indicating that there is high correlation of knowledge levels between diabetic children and their parents.
Endocrine and Metabolic Effects of Glybenclamide: Evidence for an Extrapancreatic Mechanism of Action
Authors: Feldman Jerome M , Lebovitz Harold E , Lebovitz L
Published: December 2014

The mechanism(s) by which chronic glybenclamide therapy lowers the plasma glucose and improves diabetic control was studied in patients with adult-onset diabetes mellitus. Two months of therapy with glybenclamide resulted in a striking improvement in oral glucose tolerance associated with an increase in both plasma insulin and the insulin/glucose ratio. This improvement in glucose tolerance persisted through six months of therapy. However, the plasma insulin response to glucose and the insulin/glucose ratio decreased significantly toward pretreatment levels. During the study period there were no alterations in growth hormone secretion, thyroid function, adrenal cortical function or adrenal medullary function. The data suggest that glybenclamide, a new sulfonylurea drug, may improve diabetic control and improve glucose tolerance through a mechanism other than increased insulin secretion.
Occurrence and Prevalence of Diabetic Retinopathy in Hemochromatosis
Authors: Griffiths J D , Dymock I W , Davies E W G , Hill D W , Williams Roger
Published: December 2014

In a study of retinal changes in forty-nine patients with hemochromatosis, eleven showed evidence of diabetic retinopathy by ophthalmoscopy and/or fluorescein angiography. Retinopathy was found in six of the ten patients with diabetes for ten or more years, an incidence comparable to that in diabetes mellitus. The development of retinopathy, previously regarded as rare, may be related to the longer survival of patients with hemochromatosis as a result of venesection therapy.
Evaluation of Age-adjusted Criteria for Potential Diabetes
Authors: O'Sullivan John B , Mahan Clare M
Published: December 2014

Data from Oxford, Massachusetts, indicate that one to two-hour postprandial blood sugar levels rise 4 mg. per 100 ml. per decade. In order to test whether postprandial data used for screening or diagnostic standards should be correspondingly adjusted for age, two criteria, comparable except that one resulted in a sliding scale age-adjustment, were applied to blood sugar levels obtained in Oxford in 1946–1947. The development of diabetes over the next twenty-two years provided no justification for raising these standards for increases in age. These data are considered to provide a pragmatic solution to the rise in glucose levels that occur with age, but are insufficiently precise to resolve its pathophysiologic meaning. The discussion emphasizes that the conclusion reached does not necessarily apply to data obtained following glucose ingestion.
Glucagon and the Insulin:Glucagon Ratio in Diabetes and Other Catabolic Illnesses
Authors: Unger Roger H
Published: December 2014

The biologic opposition which insulin and glucagon exert upon the liver and adipose tissue suggests that the relative concentrations of these two hormones which perfuse these tissues may determine their net nutrient balance.

A review of recent studies of plasma glucagon and insulin levels reveals that the insulin:glucagon ratio (I/G) varies inversely with need for endogenous glucose production, being lowest in total starvation and highest during loading with exogenous carbohydrate. Similarly, the infusion of the glucose precursor, alanine, which in the fasting state causes a fall in I/G, a “catabolic response,” increases I/G during a glucose infusion, an ”anabolic response,/ which must spare alanine from gluconeogenesis. The same bihormonal relationship to need for glucose production has been observed after a protein load; normally after an overnight fast I/G rises in response to a beef meal, an anabolic response, while in the carbohydrate-deprived subject, the I/G does not rise, remaining at a catabolic level; during a glucose infusion the ingestion of a beef meal induces a greatly exaggerated anabolic rise in I/G.

These findings are believed to account for certain previously poorly understood clinical observations. They may explain the so-called “protein sparing action” of glucose and the salutory nutritional effect of intravenously administered amino acid preparations when glucose is also provided in large quantities. The inability of diabetics to increase their I/G generally parallels their catabolic state, and, by stimulating glucagon but not insulin, tissue breakdown due to infection or trauma may further reduce the I/G and cause metabolic deterioration. The possible role of the I/G in the response to burns, trauma, infection, and malignancy is considered.
Glucagon and Insulin Release: Influence of Drugs Affecting the Autonomic Nervous System
Authors: Vance James E , Buchanan Keith D , Williams Robert H
Published: December 2014

Isolated rat islets of Langerhans were used to study the direct effect of autonomic nervous system compounds on immunoreactive glucagon (IRG) and insulin (IRI) release. None of the substances affected IRG release. Epinephrine (10μ.M) and norepinephrine (10μM) blocked IRI release in response to 150 mg./100 ml. glucose but did not block the effect of 300 mg./100 ml. glucose. Acetylcholine (3 μM) stimulated IRI release but isoproterenol had no effect.

Because the adenylcyclase system may play a role in adrenergic receptor mechanisms, the effects of substances which alter cellular levels of cyclic AMP were also studied. Again, none of the compounds altered IRG levels in the incubation media. Aminophylline (100 μM) stimulated IRI release but dibutyryl cyclic AMP and prostaglandin Ex were without significant effect.

The results suggested that neither autonomc nervous sys tem compounds or the adenylcyclase system directly affect IRG release. The physiolugical significance of the direct inhibitory effect of substances with alpha adrenergic properties on IRI release is questioned in view of the very high concentration required for effect.
Experimental Diabetic Hyperosmolar Syndrome in Rats
Authors: Bavli Samuel , Gordon Edwin E
Published: December 2014

The diabetic hyperosmolar syndrome occurs predominantly in maturity-onset diabetics and is characterized by extreme hyperglycemia, hyperosmolarity of plasma, and absence of ketoacidosis. A syndrome bearing a marked resemblance to the human disease can be produced in rats. The three prerequisites for the development of the experimental syndrome are: (1) moderate nonketotic diabetes (induced by either streptozotocin or alloxan) ; (2) treatment with hydrocortisone acetate; and (3) water deprivation.

Plasma glucose concentrations in cortisol-treated, waterdeprived diabetic rats ranged from 838 to 1,488 mg./100 ml. and were significantly higher than those of control diabetic or ketoacidotic animals. Neither cortisol treatment alone nor water deprivation alone was adequate to raise plasma glucose concentration above that of control diabetic rats. The blood pH, acetoacetate, and β-hydroxybutyrate of cortisoltreated, water-deprived diabetic rats did not differ significantly from the diabetic control values, but all three of these parameters were different from those of ketoacidotic rats. Neither cortisol treatment, nor water deprivation, nor a combination of the two treatments significantly affected these parameters in nondiabetic rats.

By analogy with the experimental syndrome, it is suggested that administration of corticosteroids may play a role in the development of the human hyperosmolar syndrome in some patients. Furthermore, the fact that water deprivation was necessary for the production of the experimental syndrome suggests that the extreme dehydration seen in the human hyperosmolar syndrome is not merely a consequence of hyperglycemia, but also a factor in the development of the extreme hyperglycemia.
The Stimulus-secretion Coupling of Glucose-induced Insulin Release: V. The Participation of a Microtubular-microfilamentous System
Authors: Malaisse Willy J , Malaisse-Lagae Francine , Walker Mary O , Lacy Paul E
Published: December 2014

The beta cell of the islets of Langerhans has been shown to contain a microtubular-microfilamentous system. The possible role of this system in the insulin secretory process was investigated by examining the effect upon glucoseinduced insulin secretion of mitotic spindle-inhibitors and microtubules-stabilizers. Inhibition of secretion was observed when the pieces of pancreas were pre-incubated for ninety minutes with either colchicine (0.01 to 1.0 mM) or vincristine (0.01 mM) prior to measurement of their secretory response to a high glucose concentration. Significant reduction of glucose-induced secretion was also noticed in thepresence of D2O (25 per cent or more, v/v), 2-methyl-2,4-pentanediol (0.5 to 1.0 per cent, v/v) and ethanol (1.0 per cent, v/v). The inhibitory effect of D2O was reversible. The stimulant action of glucose upon both calcium uptake and insulin biosynthesis by isolated islets was inhibited by mannoheptulose, but unaffected by either vincristine or D2O, suggesting that the latter agents did not interfere with glucose metabolism in the beta cell. These results suggest that the integrity of the microtubular-microfilamentous system is required for glucose to exert its normal stimulant action upon insulin secretion. It is hypothesized that glucose-induced calcium uptake by the beta cell could trigger the release of insulin by causing the contraction of such system, favoring the migration of the secretory granules and their extrusion in the process of emiocytosis.
Estriol Modification of the Effects of Progesterone and Human Chorionic Somatomammotropin on Glucose Tolerance and Plasma Insulin in Rhesus Monkeys
Authors: Beck Paul , Hoff Diana L
Published: December 2014

The effects of estriol and estradiol on progesterone-induced changes in glucose and insulin metabolism have been studied in mature female rhesus monkeys. The addition of striol to treatment regimens containing progesterone only or human chorionic somatomammotropin (HCS) plus progesterone resulted in improvement in mean glucose disappearance rates following intravenous glucose administration without significant changes in the mean total insulin responses to glucose. This change in glucose tolerance was primarily due to apparent improvement in peripheral glucose utilization rather than any increment in total or initial insulin responses to glucose. By contrast, the addition of estradiol to the progesterone treatment regimen produced no changes in the mean glucose disappearance rate or the plasma insulin response to glucose, although there was an increase in mean fasting glucose and insulin concentrations after estradiol + progesterone treatment. These results indicate that estriol and estradiol have different effects on glucose and insulin metabolism and suggest that estriol may modify the diabetogenic tendencies of progesterone and HCS during primate pregnancies.
Osseous Lesions of the Foot in Diabetic Neuropathy
Authors: Friedman Sandor A , Rakow Robert B , Pod D
Published: December 2014

The clinical course and foot roentgenograms of twentytwo consecutive patients with severe diabetic neuropathy were reviewed. All but one patient had skin breakdown with adequate arterial circulation. Cutaneous lesions responded well to local care, the majority healing within one month, despite widespread bone destruction. In seventeen of the twenty-two cases, (77 per cent), there were multiple bone lesions that tended to be bilateral and to follow the peripheral distribution of the neuropathy. The osseous abnormalities were radiologically indistinguishable from osteomyelitis except for a characteristic thinning of the metaphysis of proximal phalanges. Follow-up X rays showed progressive bone destruction in four patients although they had no further difficulty with their feet.

We conclude that widespread osteopathy of the foot occurs frequently in severe diabetic peripheral neuropathy and has a better prognosis than osteomyelitis, from which it must be distinguished clinically.
Fatal Venous Thrombosis in Hyperosmolar Coma
Authors: Scharf Yehuda , Nahir Menachem , Tatarsky Ilana , Arieh Judith Ben , Baruch Gellei , Edelman Shmuel
Published: December 2014

In many reported cases of hyperosmolar coma venous thrombosis was found, but no laboratory diagnosis was attempted in order to confirm or detect the thrombotic phenomena.1–3 The following is a report of a case of hyperosmolar coma in which signs of intravascular clotting appeared during the course of the illness and the patient died of massive pulmonary embolism.
Serum Immunoreactive Insulin Levels During Glucose Tolerance and Intensive Islet Stimulation
Authors: Ryan Will G , Schwartz Theodore B , Nibbe Albert F
Published: December 2014

Glucose tolerance and intensive islet stimulation tests were done on eighty-seven subjects who covered a broad range of age and glucose tolerance. The data suggest decreasing glucose tolerance with increasing age compatible with the observations of others. Over a broad range of glucose tolerance there was seen such a broad spread of serum immunoreactive insulin levels (IRI) that it was not possible to relate them directly to the degree of glucose tolerance seen. This suggested that multiple factors, including variations in peripheral resistance to insulin not attributable to known factors, are operative in determining glucose tolerance. Only when glucose tolerance was very abnormal or fasting blood sugar was elevated was there apparent decrease in serum IRI response to the stimuli used, making it difficult to attribute mild-to-moderate degrees of glucose intolerance to lack of capacity for IRI release. A close correlation between the two-hour IRI in a glucose tolerance test and the levels obtained after the stimulus of glucagon and tolbutamide suggested that the former may be an adequate reflection of islet secretory capacity.
Plasma Insulin in Reactive Hypoglycemia
Authors: Luyckx A S , Lefebvre P J
Published: December 2014

Among 663 standard four-hour oral glucose tolerance tests (OGTT) performed in a Department of Internal Medicine, forty-seven curves demonstrated reactive hypoglycemia of 45 mg. per 100 ml. or less at one or more occasions. Subsequent analysis of the records of the corresponding patients allows their partition into the following groups: IA. Obesity (11), IB. Obesity with chemical diabetes (9), II. Postgastrectomy syndrome (3), III. Chemical diabetes without obesity (1), IV. Renal glycosuria (7), V. Isolated reactive hypoglycemia (16).

In order to determine the role of plasma insulin in the pathogenesis of the syndrome, the insulin response of each group of subjects presenting reactive hypoglycemia was compared to that of a control group of similar age, sex and weight with similar pathological findings but without reactive hypoglycemia. The results indicate that plasma insulin values can not account for the reactive hypoglycemia in the groups IA, IB, III and IV, and thus other factors may be responsible for the occurrence of hypoglycemia in most cases of this syndrome.

In contrast, an exaggerated insulin response exists in group II, and in seven out of the sixteen cases of isolated reactive hypoglycemia.

No correlation was found between the presence of clinical symptoms evoking reactive hypoglycemia during the usual life and the severity of the hypoglycemia recorded during the OGTT.
Insulin Secretion Studied in the Perfused Rat Pancreas: I. Effect of Tolbutamide, Leucine and Arginine; Their Interaction with Diazoxide, and Relation to Glucose
Authors: Basabe J C , Lopez N L , Viktora J K , Wolff F W , McNeal B , Mongelli C , Wcinhardt K , Baukal A
Published: December 2014

Glucose produced a diphasic pattern of insulin secretion in the perfused rat pancreas. Both phases were blocked by diazoxide. Tolbutamide alone produced a monophasic insulin secretion which was decreased by diazoxide on an equimolar basis.

When tolbutamide was added to a perfusion containing glucose and diazoxide, it reversed the blocking effect of diazoxide on glucose by reestablishing the diphasic pattern of glucose-stimulated insulin secretion. This effect was also produced in an equimolar fashion.

Leucine induced a diphasic pattern of insulin secretion. When perfused together with glucose, an additive effect was apparent in both phases. Diazoxide blocked the secretion of insulin stimulated by leucine alone or by leucine plus glucose.

Arginine (16 mM) failed to stimulate insulin secretion, but a clear increase was observed at 26 mM concentration. An additive effect of arginine and glucose was observed in the presence or absence of 10 mg. per cent diazoxide, but was blocked by increased diazoxide concentration (25 mg. per cent). The results show that the diazoxide effect on the arginine-induced insulin secretion is related to the concentration of diazoxide used, and suggests that the stimulatory action of arginine and glucose is channelled through one identical mechanism, triggering insulin release in the beta cell.
Effect of Streptozotocin on Glucose-induced Insulin Secretion by Isolated Islets of Langerhans
Authors: Golden P , Baird L , Malaisse W J , Malaisse-Lagae F , Walker M M
Published: December 2014

The present experiments were designed to investigate the immediate action of streptozotocin upon the beta cell by measuring its effect upon glucose-induced release by isolated islets of Langerhans. The results demonstrated a dose-related inhibition of glucose-induced secretion during the first two hours of incubation, with the inhibition most marked in the second hour. The same level of inhibition was achieved in the second hour regardless of whether the drug was present for both hours or for just the first hour.

Nicotinamide showed a dose-related protection against the inhibitory action of streptozotocin whereas nicotinic acid did not. Further, nicotinamide showed a protective trend even when added one hour after streptozotocin—indicating that no irreversible change in the insulin secretory mechanism had been elicited over the first hour of incubation. An enhancement of glucose-induced secretion was observed with nicotinamide alone. Nicotinamide was not able to protect against the inhibitory action of mannoheptulose and the latter had no significant effect upon streptozotocin's action.

It is concluded that the early hyperglycemia induced by streptozotocin is the result of a direct action of streptozotocin on the beta cell and that the same biochemical lesion may be responsible for both the impairment of insulin secretion and eventual beta-cell destruction. Finally, the demonstration of a protective action of nicotinamide at the site of the beta cell suggests that the nicotinamide adenine dinucleotide (NAD) level of the beta cell may be critical for maintenance of normal function.
Assimilation of D and L I-C-14 Glucose into the Retina, Brain and Other Tissues
Authors: Dollery C T , Henkind P , Orme M L'E
Published: December 2014

Distribution of D and L l-C-14-glucose radioactivity was measured in retina, brain and other tissues by a combustion technic at short intervals following an intravenous injection in rat, rabbit and guinea pigs. Five minutes after injection, the ratios of D/L radioactivity in the retina of the three species were 23.7, 11.6 and 8.3, respectively. Similar high ratios were found in the brain but not in voluntary muscle or liver. The explanation may lie in the special characteristics of capillaries in brain and retina, which have tight intracellular junctions. Substances that enter fhe brain and retina must therefore cross the endothelial cells and cannot diffuse between them as in other tissues. The results suggest the presence of a stereospecific carrier for glucose in the endothelial cells which controls entry of glucose into the retina, as it appears to in the brain.
Insulin Secretion in Protein-Calorie Malnutrition: I. Quantitative Abnormalities and Response to Treatment
Authors: Becker Dorothy J , Pimstone Bernard L , Hansen John D L , Hendricks S
Published: December 2014

Immunoreactive insulin (IRI) responses to oral and/or intravenous (IV) glucose were measured in kwashiorkor and marasmus. Responses were expressed either as peak IRI levels attained or as insulin-glucose ratios. Similar measurements were made in normal controls.

After oral glucose, insulin secretion was abnormally low in every patient with kwashiorkor and in most of the marasmic cases. After IV glucose, normal insulin responses were noted more often, presumably associated with the greater glycemic stimulus. This was particularly noticeable in marasmus.

In both groups of subjects there was improvement after three to six weeks therapy, but this was much more striking after oral glucose. However, in many patients, insulin secretion remained subnormal or even deteriorated at this time, when nutritional status had greatly improved. Two to ten months later however, insulin levels were judged to be within normal limits in these cases. Children known to have suffered from kwashiorkor ten years previously likewise had normal insulin responses in 90 per cent of cases.

Augmented stimulation by glucose plus glucagon revealed some pancreatic insulin reserve in half the untreated patients studied. Yet the responses to augmented testing improved still further in three of five cases after therapy.

Insulin secretion is grossly impaired in kwashiorkor and marasmus. However, it is increased in many cases either by a greater glycemic stimulus or by adding glucagon to the glucose load. This suggests a “sluggishness” of insulin release after glucose under conventional conditions of testing in these cases. The disproportionate improvement after therapy in the insulin response to oral, as opposed to IV, glucose, may provide some evidence that an impaired gut betacytotrophic mechanism is partly responsible for the altered release mechanisms.