bluuebunny/crossref_metadata_2025_split huggingface dataset:
Control of Pancreatic Glucagon Secretion by Glucose
Authors: Ohneda Akira , Aguilar-Parada E , Eisentraut Anna M , Unger Roger H 
Published: December 2014

Recent questions concerning the role of glucagon as a hormone of “glucose need” prompted this evaluation of glucose-glucagon relationships. To obviate certain problems relating to the sensitivity and specificity of the glucagon radioimmunoassay of peripheral venous plasma, glucagon was assayed in pancreatic venous effluent plasma obtained from conscious dogs with indwelling catheters in the pancreaticoduodenal vein. The effect of change in glucose concentration upon the pancreaticoduodenal vein glucagon concentration was determined.
Insulin induced hypoglycemia was uniformly associated with a rise in pancreaticoduodenal vein glucagon concentration to a peak of 5.7 mμg./ml. at thirty minutes. The hyperglucagonemia continued intermittently during the hypoglycemic period but fell promptly during hyperglycemia induced by rapid injection of glucose.
Hyperglycemia, induced in fifteen dogs by glucose infusion, was accompanied by a decline of glucagon from 2.7 to 1.8 mμg./ml. Cataglycemia, induced by rapid termination of a glucose infusion, produced a rise of glucagon in three of six dogs.
Stimulation of glucagon secretion by hyperaminoacidemia was blocked by hyperglycemia induced by glucose infusion. The effect of starvation upon twenty-four-hour secretion of glucagon could not be determined in these studies. Wide variations in pancreaticoduodenal vein glucagon concentration made meaningful comparison of day-to-day changes impossible.
A statistically significant negative correlation was observed between rapidly induced change in plasma glucose concentration and change in pancreaticoduodenal vein glucagon levels. The findings are compatible with the view that glucagon is a hormone of glucose need, which probably functions in the moment-to-moment regulation of blood glucose homeostasis and the maintenance of the so-called “normal” blood glucose limits.
Relative Effects of Pregnancy, Human Placental Lactogen and Prednisolone on Carbohydrate Tolerance in Normal and Subclinical Diabetic Subjects
Authors: Kalkhoff R K , Richardson B L , Beck P 
Published: December 2014

Six subclinical diabetic postpartum women with normal standard glucose tolerance tests (GTT) but diabetic responses during prednisolone glucose tolerance tests (PGTT) had a third GTT performed after an overnight infusion of human placental lactogen (HPL). Similar studies were done on six control postpartum women with normal GTT and PGTT. HPL infusions produced plasma levels of the hormone that were comparable to concentrations observed in late pregnancy.
In the control group HPL infusion had minimal effects on GTT, and no significant changes of plasma immunoreactive insulin (IRI) were observed. Higher, though normal, glucose levels during PGTT were associated with corresponding elevations of IRI.
HPL infusion, like prednisolone administration, induced diabetic curves in the subclinical diabetic subjects, and IRI levels did not rise significantly above corresponding GTT levels until the second hour even though abnormal hyperglycemia was established between one-half and one hour. Both hormones increased fasting plasma glucose levels, but only prednisolone elevated fasting levels of nonesterified fatty acids.
Three control and three diabetic women were also studied prepartum. Neither pregnancy nor postpartum HPL infusion altered GTT in the normal group. HPL administration to the diabetic subjects induced deterioration of carbohydrate tolerance that was more pronounced than that observed prepartum. In both groups plasma IRI was higher during prepartum testing.
These observations suggest that normal women resist degrees of diabetogenic stress that produce abnormal GTT in subclinical diabetic patients. The latter group tolerated pregnancy better than postpartum HPL or prednisolone administration presumably because of the greater adaptive hyperinsulinemia that occurred during gestation.
Immunology Conformation and Biological Activity of Insulin
Authors: Arquilla Edward R , Bromer William W , Mercola Daniel 
Published: December 2014

Evidence is presented that insulin antibodies produced by strain 2 guinea pigs bind preferentially to antigenic determinants related to the N-terminal B chain, N-terminal A chain, and lysine at position B-29. Strain 13 antibodies appear to bind preferentially to antigenic determinants involving the C-terminal A and C-terminal B chains. It appears that the C-terminal A chain and C-terminal B chain, in close proximity to each other, form a center rich in aromatic amino acids. This center appears to be directly related to the antigenic determinants with which the strain 13 antibodies combine, but in addition, is also important for the conformation of distant antigenic determinants. Insulin derivatives which have the greatest distortion of antigenic determinants (desoctopeptide, iodinated, and triconjugated fluorescent insulin) also have negligible biologic insulin activity. Desalamine-desasparagine insulin and diconjugated fluorescent insulin which by their immunologic reactivity appear to have distortions of antigen determinants of an intermediate degree have trace amounts of biologic activity. The insulin derivative with the least distortion of antigenic determinants (monoconjugated fluorescent insulin) had more biologic insulin activity than any of the derivatives studied.
Physical measurements involving circular dichroism and ultra centrifugal analysis confirm the immunologic observations concerning the conformations of insulin and the insulin derivatives.
These studies show that any change in conformation results in a proportionate decrease of biologic activity of insulin. Therefore, the molecular mechanism of insulin action probably involves a complementary fit with a site either on or with insulin responsive cells.
Improved Glucose Disappearance Following Repeated Glucose Administration: Serum Insulin, Growth Hormone and Free Fatty Acid Levels During the Staub-Traugott Effect
Authors: Szabo Andrew John , Maier Jacqueline J , Szabo Olga , Camerini-Davalos Rafael A 
Published: December 2014

The Staub-Traugott effect, the phenomenon of improved tolerance to repeated glucose administration, was investigated in fifteen healthy volunteers. Two glucose loads were administered intravenously forty-six minutes apart. Blood samples were taken periodically after each glucose infusion. The second glucose load was given immediately after the first sampling period. The glucose disappearance rate (K) improved after the second infusion from 2.04 ± 0.23 to 2.87 ±0.16 (p &lt; 0.001).
Serum immunoreactive insulin levels rose promptly after the glucose infusions, but while a decrease was noted following the first peak, the levels remained persistently elevated after the second glucose load. Growth hormone levels decreased and were slightly lower yet six to nine minutes after completion of the infusions.
A striking reduction of free fatty acid levels followed the first glucose load; values fell to 50 per cent of the fasting levels prior to, and decreased even further following, the second infusion. Thus, the improved K of the second glucose tolerance test was associated with already diminished serum free fatty acid levels.
Influence of Physiologic Fluctuations in Plasma Growth Hormone on Glucose Tolerance
Authors: Yalow Rosalyn S , Goldsmith Stanley J , Berson Solomon A 
Published: December 2014

In oral glucose tolerance tests (GTT) performed three, four, or six hours after a previous GTT, six hours after a combined protein-glucose tolerance test or two and onehalf hours after intravenous insulin, impairment in tolerance could be closely correlated with the magnitude of the growth hormone secretory response in the previous procedure. These observations support the physiologic role of growth hormone in determining glucose tolerance.
Impairment in glucose tolerance was generally associated with an augmented integrated plasma insulin response and improvement in glucose tolerance was frequently seen in association with a lesser plasma insulin response. These observations support the view that plasma insulin follows blood glucose but that the rate of glucose disposal is determined by factors other than the level of plasma insulin alone.
Studies on the Ability of Compounds to Block the Diabetogenic Activity of Streptozotocin
Authors: Dulin William E , Wyse Beatrice M 
Published: December 2014

Evidence is presented that the early hyperglycemia (two to four hours after injection) following streptozotocin administration is not a result of an interference with insulin action, since streptozotocin did not block insulin action on skeletal muscle in vitro.
Compounds with known metabolic effects were tested for their ability to block streptozotocin-induced diabetes. Mannoheptulose, glucosamine, diazoxide, NAD, glucose, epinephrine, 3,5-dimethylpyrazole, 3-carboxy-5-methylpyrazole, glutamic acid, glycine, asparagine, cysteine, sodium tolbutamide, guanidoacetic acid, glutathione, p-aminobenzoic acid, and ethyl alcohol were ineffective as blocking agents. Pretreatment with pyrazinamid blocked streptozotocin diabetes,but was ineffective following streptozotocin treatment. 2-carboxypyrazine (the metabolite of pyrazinamide) did not block streptozotocin diabetogenic activity. Administration of 2-deoxyglucose blocked streptozotocin-induced diabetes; this is postulated to be the result of an interference with streptozotocin transport into the β cell.
Pretreatment with nicotinamide, or treatment as long as two hours after streptozotocin, blocked the diabetogenic effect of streptozotocin. Nicotinic acid was ineffective. It is postulated that streptozotocin interferes with NAD formation in the β cell, and that nicotinamide treatment abolishes the streptozotocin effect by its ability to maintain ah adequate concentration of NAD in the β cell.
Streptozotocin Diabetes in the Mouse and Guinea Pig
Authors: Brosky G , Logothetopoulos J 
Published: December 2014

A single injection of streptozotocin into mice produced an extensive necrosis of the beta cells resulting in permanent diabetes. The histological changes in the islets were similar to those described after the injection of alloxan. The regenerative capacity of beta cells which survived the cytotoxic injury was limited.
Hypoglycemia induced by an injection of insulin or hyperglycemia induced by glucose injections sensitized the beta cells to streptozotocin. In contrast, injection of insulin antibody effectively protected the beta cells from the cytotoxic injury.
Streptozotocin caused widespread necrosis of the beta cells of the guinea pig and the obese hyperglycemic mouse. Both these species had proven resistant to the diabetogenic effect of alloxan.
Diabetic guinea pigs were observed for eight months, without reversion of the diabetic syndrome.
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.
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 &lt; 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 &lt; 0.01) while the difference between the insulin responses following the 75 gm. and 1.75 gm./kg. loads had lower significance (p &lt; 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.
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.
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.
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.