bluuebunny/crossref_metadata_2025_split huggingface dataset:
HLA, Islet Cell Antibodies, and Types of Diabetes Mellitus
Authors: Nerup J , Platz P , Ryder L P , Thomsen M , Svejgaard A 
Published: September 2013

Insulin-dependent diabetes mellitus, in contrast to non-insulindependent diabetes mellitus, is associated with HLA factors B8, BW15, and B18.
Recent studies have shown the association to be even stronger with HLA, DW3, and DW4 and have produced evidence for the existence of two “diabetogenic” genes predisposing to insulindependent diabetes in different ways. Evidence to suggest the existence of a gene—associated with DW2—that protects against the disease is accumulating.
Islet cell antibodies are a feature of insulin-dependent diabetes mellitus and can be seen, in most cases, at the time of diagnosis.
C-Peptide in Conditions Other Than Diabetes Mellitus
Authors: Horwitz David L , Rubenstein Arthur H , Mako Mary E , Cruz Angelita , Blix Petra M 
Published: September 2013

Measurement of serum and urinary C-peptide has been shown to be of value in several conditions other than diabetes mellitus. It is particularly useful because it can distinguish endogenous beta cell secretion from exogenously administered insulin and because circulating insulin-binding antibodies do not interfere with its measurement. Because the liver removes little, if any, C-peptide, peripheral blood values may more accurately reflect beta cell secretion than do peripheral insulin levels.
Clinically, serum C-peptide has been most useful in diagnosing hypoglycemic disorders. Diagnosis of insulinomas is facilitated in both diabetic and nondiabetk patients, and surreptitious insulin injection is readily detected. In studies of insulin regulation, circulating C-peptide has been used to demonstrate suppression of endogenous insulin secretion by exogenous insulin. Peripheral insulin and C-peptide levels have been compared in studies of the role of the liver in states of altered insulin homeostasis. Because of its higher urinary clearance, determination of urinary C-peptide is preferable to urinary insulin measurement in situations where frequent blood sampling is impossible or difficult to accomplish.
Immunoreactive Glucagon Responses to Oral Glucose, Insulin Infusion and Deprivation, and Somatostatin in Pancreatectomized Man
Authors: Werner Phillip L , Palmer Jerry P 
Published: September 2013

In a group of pancreatectomized subjects, immunoreactive glucagon (IRG) concentrations were normal after an overnight fast, increased after oral glucose, were not suppressed by somatostatin (SRIF) or insulin, and in two of four subjects they rose with an arginine infusion. Even though the SRIF infusion failed to lower IRG, there was a fall in plasma glucose concentration in both subjects. In two subjects, endogenous hyperglycemia occurred during insulin withdrawal without a rise in IRG, and, in one subject, mild diabetic ketoacidosis developed with only a minimal rise in IRG.
These results support the presence of an extrapancreatic source of IRG in man. Secretion from these extrapancreatic alpha cells appears to be regulated differently than secretion from pancreatic alpha cells.
Alloxan Stimulation and Inhibition of Insulin Release from Isolated Rat Islets of Langerhans
Authors: Weaver Daniel C , McDaniel Michael L , Naber Stephen P , Barry C David , Lacy Paul E 
Published: September 2013

The rate of alloxan-induced insulin release was measured from rat islets maintained in a simple perifusion system. Insulin release during the five-minute exposure to alloxan reached its maximum rate after two to three minutes of the exposure and then rapidly declined. This insulin release was dependent upon extracellular calcium and was associated with an increased 45Ca uptake by isolated islets. Once exposed to alloxan, however, the islets did not release insulin when stimulated again with D-glucose or alloxan. These effects of alloxan on insulin release (stimulation and subsequent inhibition) and the increased 45Ca uptake were prevented by the presence of 3-0-methyl-D-glucose during the alloxan exposure. These findings indicate a close correlation between alloxan-induced insulin release and the subsequent inhibition of further insulin release.
D-glucose, when present during the entire five-minute exposure to alloxan, protected competitively against alloxan inhibition of insulin release. In addition, D-glucose, when present immediately after brief (one to three minutes) alloxan exposures, reversed some of the subsequent inhibition of insulin release. These findings suggest that alloxan and D-glucose were competing for a common site on the β-cell. The possibility of this site being a receptor responsible for the initiation of insulin release is discussed.
In-vitro and In-vivo Responsiveness of Muscle and Adipose Tissue to Insulin in Rats Rendered Obese by a High-fat Diet
Authors: Susini C , Lavau M 
Published: September 2013

The influence of insulin on [6-14C] glucose metabolism was assessed in vitro and in vivo in epididymal adipose tissue and diaphragm of rats fed either a low-fat (9 per cent fat cal.) or a high-fat diet (72 per cent fat cal.) In vitro, diaphragm of fat-fed rats showed a lower glucose uptake than that of rats fed the low-fat diet, but had identical glycogen labeling and lactic acid production and a strongly reduced 14CO2 production. Responsiveness of these pathways to insulin was unaltered by the fat content of the diet. The adipose tissue of fat-fed rats versus that of rats fed the low-fat diet showed: a higher lactic acid production and more efficient glycerogenesis and glycogenesis, all of these pathways being responsive to insulin; a lower glucose uptake and a strongly depressed fatty acid labeling, these two pathways being unresponsive to insulin. In-vivo labeling of glycogen in diaphragm in both basal and insulin-stimulated conditions was identical in the two groups of rats. In adipose tissue the amount of 14C sequestered in the ghyceride-glycerol moiety was the same in the two groups in basal and insulin-stimulated conditions, whereas the labeling of the fatty acid moiety and its increment with insulin were reduced by more than 99 per cent by the high-fat diet.
These results show that alterations in fat content of the diet lead to differences in response to insulin that are pathway- and organ-specific.
Noninvasive Estimation of Myocardial Performance in Patients with Diabetes: Effect of Alcohol Administration
Authors: Rubier Shirley , Sajadi M Reza M , Araoye Matthew A , Holford Fred D 
Published: September 2013

Systolic time intervals (STIs) were determined in 19 diabetic patients under age 50 (mean age 35.2 years) and 24 normal control subjects (mean age 30.6 years). Preëjection period (PEP), left ventricular ejection time (LVET), and PEP-LVET ratio were obtained by the conventional manner. Preëjection period index (PEPI) and left ventricular ejection time index (LVETI) were derived by Weissler's formula.14 The isovolumic relaxation time (IVRT) was measured: (1) from the aortic component of the second heart sound of the phonocardiogram to the rapid opening anterior motion of the anterior leaflet of the mitral valve on echocardiogram (A2D1), (2) and to the “0” point of the apexcardiogram (A2O). PEP, LEVT, PEPI, LVETI, and PEP/LVET ratio were statistically similar in diabetics and controls. However, the A2D1 was longer in diabetics (71.2 ± 3.4 msec.) than in control subjects (59.5 ±3.1 msec.) (p &lt; 0.02). Effects of oral ethanol (0.7 gm./kg.) administered over 20 minutes to 12 diabetics (group 1) and seven control subjects (group 2) were studied before and at 15, 30, 60, and 90 minutes after ingestion.
No change in STIs occurred in group 2 (controls) but the heart rate, PEPI, and PEP/LVET ratio rose in group 1 (diabetics). There were significant differences in PEPI and PEP/LVET ratio between groups 1 and 2, 30 and 60 minutes after alcohol. IVRT remained unchanged. Maximum blood alcohol levels for both groups were comparable at 60 minutes, (67.8 ± 5.2 mg./100 ml. in group 1 and 66.7 ± 7.5 mg./100 ml. in group 2). Glucose levels, although higher in group 1, remained stable throughout for both groups. Lactate levels, after alcohol ingestion, were comparable in both groups. Although the only evidence of myocardial dysfunction noted in diabetic patients in the resting state was the increase in IVRT, their response to alcohol revealed further changes in cardiac function not seen with such low doses of ethanol in normal individuals.
Loss of Insulin Response to Ingested Amino Acids After Jejunoileal Bypass Surgery for Morbid Obesity
Authors: Moxley Richard T , Lockwood Dean H , Amatruda John M , Tobin Jordan D , Pozefsky Thomas 
Published: September 2013

Amino acid tolerance tests were performed before and after jejunoileal bypass surgery for morbid obesity to determine whether an enteric factor(s) originating in the bypassed jejunum and/or ileum potentiates the insulin response to oral nitrogen loading.
Preoperati vely a 30-gm. mixture of amino acids given orally evoked a larger peak insulin response than an intravenous load yielding comparable plasma amino acid elevations (82 ± 17 μU./ml. versus 38 ± 8 μU./rnl., p &lt; 0.05). Four months after operation, basal insulin concentrations were 46 per cent (p &lt; 0.001) of preoperative values. After surgery the response to intravenous amino acids was preserved when expressed as percentage increase above basal. In contrast, the peak increment and the percentage increase in insulin secretion after 30-gm. oral amino acid loading was significantly blunted (p &lt; 0.005). A smaller amino acid load (16.5 gm.) was given preoperatively to duplicate the plasma amino acid elevations seen postoperatively with the 30-gm. mixture given by mouth. The insulin response postoperatively was still significantly lower (167 ± 33 per cent versus 98 ± 16 per cent, p &lt; 0.05). After various explanations for the diminished postoperative insulin release following oral amino acid ingestion are considered, the results are best explained by the loss of an enteric insulinotrophic factor(s) normally released by the bypassed portions of jejunum or ileum in response to ingested protein.
Physical Characteristics of Insulin Receptors on Renal Cell Membranes
Authors: Blanchard Richard F , Davis Paul J , Bias Susan D 
Published: September 2013

Certain physical characteristics of the insulin-kidney-membrane interaction in dog renal cortex have been defined. Two classes of binding sites were identified: the high-affinity-low-capacity site had a Ka of 1.3 × 109 M1 and a capacity of 43 fmols per milligram membrane protein. The lower-affinity site Ka was 3.7×107 M-1. Saturabili t y of receptor sites could not be demonstrated at any insulin concentration. At 21° C, binding of insulin was maximal after 60 minutes of incubation, with a t1/2of &lt;1.0 minute. Specific binding of 125I-insulin was proportional to protein concentration when the fraction of insulin bound was not excessive. Proinsulin and desoctapeptide insulin displaced labeled insulin in proportion to their known biologic activities (insulin&gt;proinsulin&gt;desoctapep-tide insulin). Arginine vasopressin and glucagon did not compete with native (labeled) insulin for binding sites. The kinetic properties of the kidney insulin-receptor sites are similar to those previously reported for liver and fat cell receptors.
A comparison of specific binding of 125I-insulin to kidney and liver membranes in the presence of various cation concentrations showed no enhancement of binding in either tissue by NaCl as high as 2 M and KC1 up to 50 mM. In contrast, 25 mM CaCl2 caused an increase in specific binding from 3.8 to 7.7 fmols 125I-insulin per milligram protein in kidney and from 1.0 to 2.1 fmols per milligram protein in liver. MgCl2 (10 mM) increased binding of insulin from 3.5 to 7.3 fmols per milligram in kidney and from 1.0 to 2.1 fmols per milligram in liver. EDTA (2mM) had no intrinsic effect on binding but reversed (by 50 per cent) the Ca2+ -mediated enhancement of binding. Divalent cations appeared to influence both high and low affinity sites.
125I-insulin degradation occurred as a function of total insulin concentration in the kidney membrane system and reduced the amount of “bindable” free hormone. The process was not saturable below 10-6 M insulin. Degradation effects influenced calculated equilibrium constants to a minimal degree.
Immunologic Insulin Resistance
Authors: Davidson John K , DeBra Donald W 
Published: September 2013

The efficacy of sulfated beef insulin for plasma glucose control in 35 patients with immunologie insulin resistance was studied. Patients were on a mean dose of 550 U./day (range 200–2,000) of U-500 regular beef insulin. Mean maximum 125I-insulin-binding capacity was 191 mU./ml. serum (range 13–1,080). Mean in vivo half-life (T½) of 125I-regular beef insulin was 614 minutes (range 114–1,300), as against a mean T½ of 13.9 minutes (range 11.8–16.5) in normal controls.
Treatment was successful in 34 patients and unsuccessful in one with lipoatrophic diabetes. The mean initial dose of sulfated insulin was 89 U./day (range 15–400) and at three months was 66 U./day (range 20–400). Twenty-eight patients who responded and survived have been on sulfated insulin for a mean of 39 months (range 2–66) and are on a mean dose of 25 U./day (range 0–100). The mean maximum binding capacity fell to 9 mU./ml. (range 0–34) during therapy (p&lt;0.01). Mean 125I-insulin T½ fell from 614 to 249 minutes after sulfated insulin therapy (p&lt;0.001). A comparative study of 15 patients on consecutive days showed a 35sulfated insulin T½ of 60 minutes (range 15–94) and a mean 125I-regular insulin T½ of 246 minutes (range 62–560, p&lt;0.001).
These results indicate that sulfated insulin is less antigenic than regular beef insulin and combines less avidly with human antibodies to regular beef insulin. The response to sulfated insulin therapy was significantly better than the response reported by other investigators to pork insulin or to steroid therapy in similar patients.
Monoamine Oxidase, Catechol-O-methyltransferase, and Norepinephrine Levels in Mice with the Hereditary Obese-hyperglycemic Syndrome
Authors: Feldman Jerome M , Henderson Joan H 
Published: September 2013

There is some evidence that there are abnormalities in catecholamine metabolism in patients with obesity and diabetes mellitus. In this study we determined the tissue levels of catecholamine-metabolizing enzymes (monoamine oxidase [MAO] and catechol-O-methyltransferase [COMT]) and norepinephrine (NE) in mice with the hereditary obese-hyperglycemic syndrome (ob/ob mice). The ob/ob mice have greater MAO activity in their kidneys (+ 43 per cent), testes (+ 51 per cent), and white adipose tissue (+ 87 per cent) than their normal-weight Httermates. There is no difference in MAO activity of pancreas, liver, brain, brown fat, heart, and islets of Langerhans in ob/ob and normal mice. The ob/ob mice have less COMT activity in their liver (−39 per cent) than normal mice. There is no difference in COMT activity in the kidney, testis, pancreas, and brain between ob/ob and normal mice. The Michaelis constant of kidney MAO for the tryptamine substrate is similar in normal and obese mice, suggesting that the increased MAO activity is due to a greater amount of tissue MAO rather than an altered affinity of MAO for the tryptamine substrate.
The ob/ob mice have a persistent elevation in MAO activity despite eugiycemia (older mice) and a reduction in weight (caloric restriction), suggesting that the elevated MAO activity in ob/ob mice is a primary rather than a secondary disturbance. The total NE content of kidney, white fat, and brown fat is similar in ob/ob and normal mice. The islet NE content is less than 3 pg. per islet in ob/ob and normal mice.
C-Peptide Secretion During the Remission Phase of Juvenile Diabetes
Authors: Heinze E , Beischer W , Keller L , Winkler G , Teller W M , Pfeiffer E F 
Published: September 2013

C-peptide secretion was studied in eight juvenile diabetics during the remission phase of the disease. The release of C-peptide was measured after a (1) normal intravenous glucose tolerance test, (2) a double glucose tolerance test, (3) an arginine infusion, and (4) after an intravenous glucose tolerance test followed by an arginine infusion. Under all conditions the intravenous glucose load had only a minimal effect on the secretion of C-peptide, while arginine alone or after the intravenous glucose tolerance test stimulated the release of the peptide in all patients. Pretreatment with glucose did not augment the effect of arginine on C-peptide release.
The results indicate that during the remission phase of juvenileonset diabetes the endocrine pancreas does not recognize glucose as an appropriate signal for C-peptide release and cannot transform the amplifying effect of glucose into a higher hormonal secretion rate.
Further Characterization of the Impaired Bactericidal Function of Granulocytes in Patients with Poorly Controlled Diabetes
Authors: Nolan Charles M , Beaty Harry N , Bagdade John D 
Published: September 2013

Granulocytes of patients with diabetes mellitus have an impaired capability to engulf bacteria, but it is not clear whether subsequent intracellular killing, which has separate energy sources, is also defective.
We separately assayed engulfment and intracellular killing of Staphylococcus aureus 502a by granulocytes of 17 diabetic patients with fasting hyperglycemia to better characterize the phagocytic defect. Diabetic granulocytes engulfed a smaller proportion than controls of a 106 inoculum of bacteria after 20 minutes of incubation in vitro (56.8 ± 9.4 per cent versus 72.4 ± 3.6 per cent, mean ± S.E. of 10 patients and paired controls, p &lt; 0.05), but after 60 minutes of incubation this defect had disappeared. Intracellular killing of staphylococci by granulocytes from seven diabetics (68.6 ± 8.9 per cent of a 106 inoculum) was less (p &lt; 0.01) than that of paired controls (80.3 ± 4.5 per cent) after two hours of incubation. Seven patients were retested during a period of improved diabetes' control; intracellular killing of staphylococci by granulocytes of six of the seven increased considerably and either exceeded the paired control value or approached it to within 75 per cent.
These data suggest that a primary defect exists in intracellular killing of staphylococci by granulocytes from poorly controlled diabetics in addition to that previously shown in engulfment. This bactericidal activity becomes more efficient when the diabetes is brought under better control.
Impairment of Glucose-induced Insulin Secretion and Glucose Tolerance During Colchicine Treatment
Authors: Shah Jayendra H , Wongsurawat Nirandon 
Published: September 2013

The effect of acute and chronic colchicine treatment on glucose induced immunoreactive insulin secretion and glucose tolerance was examined in fasting, unanesthetized, and unrestrained rats with indwelling jugular vein and aortic catheters. In the first study, intravenous glucose tolerance tests were performed by rapidly administering a glucose pulse (150 mg. intravenously) one hour after acute treatment with colchicine (0.5 mg. per kilogram of body weight, intravenously) or vehicle (control). Acute colchicine treatment caused significant suppression of glucose-induced insulin secretion and also markedly impaired glucose disappearance rates. In the second study, chronic colchicine treatment (in the lower dose of 0.2 mg. per kilogram of body weight, intraperitoneally, daily for 10 days) caused significant suppression of biphasic insulin secretion in response to a primed-constant glucose infusion (150 mg. of glucose pulse followed by 6 mg. per minute constant glucose infusion for 60 minutes) as compared with control rats (vehicle injection, intraperitoneally, daily for 10 days). Due to this marked decrease in biphasic insulin secretion, serum glucose concentrations were significantly higher between 10 and 45 minutes in the colchicine-treated rats than in the control rats.
Therefore, acute and chronic colchicine treatment causes marked inhibition of glucose-induced insulin secretion and impairment of glucose tolerance in the intact rat. These observations suggest there is a need to evaluate carbohydrate metabolism in patients receiving colchicine treatment.
The Regulation of Plasma Ketone Body Concentration by Counter-Regulatory Hormones in Man: III. Effects of Norepinephrine in Normal Man
Authors: Schade David S , Philip Eaton R 
Published: September 2013

We examined the mechanism of norepinephrine's ketogenic activity in normal man. The contribution of norepinephrine's lipolytic activity to the subsequent ketosis was assessed by comparing the degree of ketosis attained during hormone infusion and the degree of ketosis observed after heparin-induced free fatty acid substrate generation. In addition, we examined the effect of norepinephrine infusion on the plasma concentration of other stress hormones (glucagon, cortisol, and growth hormone) with the experimental protocol.
The results obtained during norepinephrine infusion into normal man demonstrated that norepinephrine's lipolytic activity was not the principal determinant of its ketogenic activity. In fact, less than 50% of norepinephrine's ketogenic activity could be attributed to the rise in plasma free fatty acid concentration. Furthermore, the ketosis that resulted from plasma norepinephrine elevation may have been a direct hormonal effect at the liver or may have been secondary to the norepinephrine-induced elevation of glucagon and/or suppression of insulin.
Our results emphasize the important role that endogenous insulin secretion plays on modulating the ketogenic effects of the stress hormones. Thus, norepinephrine, which suppresses plasma insulin secretion, is markedly ketogenic compared with the normal ketogenic response to glucagon, in spite of the fact that both of these stress hormones may activate ketogenesis via cyclic AMP formation. In conclusion, this study, in concert with a previous study in diabetic man, firmly established norepinephrine as a major ketogenic hormone in man.
Patient-controlled Portable Insulin Infusion Pump in Diabetics
Authors: Bojsen Jørgen , Deckert Torsten , Kølendorf Klaus , Lørup Birthe 
Published: September 2013

Ten patients with unstable insulin-dependent diabetes mellitus, mean duration 17.5 yr, all treated with highly purified porcine NPH insulin twice daily, were placed on highly purified porcine regular insulin subcutaneously four times daily for 2 days. Thereafter a preplanned intravenous insulin infusion was given for 54 h. Insulin in an amount corresponding to 24-h insulin requirement was infused by a portable infusion pump. Immediately before the main meals the prandial infusion program was released by the patients by pushing a button. Capillary blood glucose was taken every 30 min during the day and every 2 h during the night. Endogenous insulin secretion was calculated by measuring the C-peptide response after 1 mg of glucagon intravenously. Insulin antibodies were measured in all patients.
Insulin antibody concentration was low in most cases, and only one patient reacted to glucagon by a significant but low rise of C-peptide. After an equilibration period of 5 h, mean blood glucose (MBG) was in the physiologic range in 6 of 10 patients during the infusion period. MGB in the 10 diabetics averaged 5.5 ±1.0 mmol/L (mean ± SD) compared with 4.4 ± 0.4 mmol/L in nondiabetic controls. The mean amplitude of glycemic excursions (MAGE) was 4.1 ±1.4 mmol/L (mean ± SD) against 1.8 ± 0.6 mmol/L in control subjects. MBG, MAGE, and glucosuria were significantly reduced on the infusion days compared with the days on subcutaneous insulin.
It is concluded that near-normal blood glucose fluctuations can be obtained in unstable diabetics by a preplanned prandial insulin infusion program activated by diabetic patients themselves.