bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative Determination of the Interaction Between Epinephrine and Various Insulin Releasers in Man
Authors: Efendić Suad , Luft Rolf , Cerasi Erol 
Published: September 2013

Epinephrine significantly inhibited glucose-induced insulin release in man, the threshold dose being about 20 ng./kg. per minute. Maximal effect was attained with 60 ng./kg. per minute. In the presence of the threshold epinephrine dose, the dose-response curve for glucose-induced insulin release seemed to be displaced almost in parallel to the right of the control, suggesting competitive Inhibition. With the high epinephrine dose the inhibition of insulin release was of a noncompetitive nature.
Epinephrine did not significantly suppress insulin release induced by either arginine or tolbutamide as compared with the effect of these insulinagogues when given at normoglycemia. Only in the case of glucagon did the high epinephrine dose (90 ng./kg. per minute) markedly inhibit the insulinogenic effect of the hormone (p&lt;0.001) even when the effect of glucagon at normoglycemia was used as control.
Since glucose exerted synergistk effects on insulin release in-duced by the other insulinagogues (arginine, glucagon, and tolbutamide), the insulinogenic effect of these insulinagogues In the presence of epinephrine was compared with their effect under hyperglycemie conditions similar to those obtained with epinephrine alone. It was found that epinephrine at a dose of 30 ng./kg. per minute totally inhibited the synergism between the hyperglycemie and the insulinagogues on insulin release. The greater the synergism—as with arginine and glucagon—the larger was the percentage inhibition by epinephrine. A threefold increase in the epinephrine dose further reduced the insulin response.
Our experiments suggest that epinephrine—in the doses used—inhibited the effect of glucose on insulin release. This effect occurred regardless of whether glucose was used as the sole stimulator of insulin release or was used in synergism with such insulinagogues as arginine, tolbutamide, or glucagon.
Effects of Ingestion of Triglyceride or Galactose on Secretion of Gastric Inhibitory Polypeptide and on Responses to Intravenous Glucose in Normal and Diabetic Subjects
Authors: Ross S A , Dupre J 
Published: September 2013

Responses of plasma immunoreactive gastric inhibitory polypep-tide (IRGIP) to oral triglycéride or galactose were compared in normal and mildly diabetic (non-insulin-dependent) subjects. After triglyceride the responses of IRGIP were similar, but after galactose those of the diabetics were slightly exaggerated. Both stimuli evoked increments of plasma immunoreactive glucagon (IRG) in diabetics but not in normal subjects. Plasma immunoreactive insulin (IRI) did not change.
In normal subjects given oral triglyceride or galactose followed by intravenous (I.V.) glucose the early-phase response of plasma IRI was enhanced and glucose tolerance improved. In the diabet-ics, oral triglyceride did not affect insulin release or glucose tolerance after I. V. glucose; oral galactose elicited a slight increase of insulin release without improving glucose tolerance. In the diabetics the rise in plasma IRG after ingestion of triglyceride or galactose was maintained after I. V. glucose.
It is concluded that endogenous GIP is insulinotropic and that there is partial resistance to this action in diabetes. The results were compatible with feedback inhibition of GIP secretion by insulin and with the suggestion that the rise of plasma IRG associated with secretion of GIP in diabetics may be due to the glucagono-tropic action of this peptide.
Effect of Priming of Amino Acids on Insulin and Growth Hormone Response in the Premature Infant
Authors: Reitano G , Distefano G , Vigo R , Giunta L , Grasso S 
Published: September 2013

Glucose, α-amino nitrogen, serum insulin, and HGH were studied in preterm infants during the first 24 hours of life.
Glucose infusion (1.25 gm.) resulted in a slight elevation of serum insulin. When this amount of glucose was infused during the last 30 minutes of a two-and-a-half-hour infusion of a mixture of essential amino acids, there was a rapid and striking increase in serum insulin. However, this increase was not associated with a faster glucose disposal rate. The administration of this mixture of amino acids doubled the basal level of α-amino nitrogen, and during the first two hours, before glucose infusion, it caused a significant rise of serum insulin and HGH. In both cases glucose caused an increase of HGH secretion that was not significantly different in the two groups of infants.
Bimodality of Fasting and Two-hour Glucose Tolerance Distributions in a Micronesian Population
Authors: Zimmet P 
Published: September 2013

While frequency distributions of glucose concentrations in Caucasian populations are unimodal, bimodality has been described in the Pima Indians, a population with an extremely high prevalence of diabetes.
Venous plasma glucose concentrations at fasting and after a 75-gm. oral glucose load were determined in 596 Nauruans, a Micronesian population with a diabetes prevalence of the same order as the Pima Indians. In both sexes and in subjects 10 to 19 years, the frequency distributions of the logarithms of the fasting and two-hour glucose values were clearly unimodal. In most sex and age groups of 20 years and older, the frequency distributions of fasting and two-hour glucose values were bimodal and consistent with a model of two overlapping Gaussian distributions.
This population is characterized by marked obesity. However, there was no significant difference in the degree of obesity between subjects in the first and second curves of the bimodal distribution. This makes it unlikely that the bimodality is a consequence of the marked obesity seen in both the Pima and Nauru populations.
The data show that among Nauruans, as with the Pimas, the frequency distribution of glucose concentrations can be used to separate the population into normal and hyperglycemic groups.
Regional Distribution and Concentration of Pancreatic Polypeptide in the Human and Canine Pancreas
Authors: Gersell Deborah J , Gingerich Ronald L , Greider Marie H 
Published: September 2013

The regional concentrations of pancreatic polypeptide (PP), insulin, and glucagon and the cellular distribution of PP were studied in 13 human and nine canine pancreases by radioimmunoassay, immunoperoxidase localization, and cell quantitation. PP concentration was highest in both the uncinate process and the head of the human pancreas and in the right lobe of the canine pancreas. In contrast, glucagon and insulin levels were higher in the body and tail of both the human and canine pancreases.
Human F-cells, which contain PP, were located primarily at the periphery of the islets, although a few F-cells were scattered throughout the ducts and acini. Canine F-cells were located in ducts, acini, and islets; the relative proportion of canine F-cells in the endocrine and exocrine tissues differed according to location.
Cellular quantitation of F-cells in both species correlated significantly with the tissue concentration of PP in all regions studied, validating the use of morphometric techniques to quantitate the regional distribution of PP.
Counterregulatory Hormonal Responses to Rapid Glucose Lowering in Diabetic Man
Authors: Lilavivathana Usah , Brodows Robert G , Woolf Paul D , Campbell Robert G 
Published: September 2013

To define whether rapid rate of fall in blood glucose stimulates counterregulatory hormonal responses in diabetic man, blood glucose in eight hyperglycemic diabetic subjects was rapidly lowered by intravenous insulin administration. Despite precipitous declines in blood glucose, plasma epinephrine and growth hormone remained virtually unchanged. In contrast, norepinephrine and cortisol increased significantly (P &lt; 0.025) in the face of hyperglycemia or euglycemia, while glucagon was suppressed (P &lt; 0.025). A transient modest fall in mean arterial pressure and a rise in pulse rate were noted. No correlation was observed between glucose disappearance rate or decrement in glucose concentration and the hormonal responses. After sham insulin administration, no change was observed in plasma epinephrine, norepinephrine, and cortisol levels.
These findings suggest that rate of fall in blood glucose per se is not a primary signal for counterregulatory hormonal response. Cortisol but not growth hormone release during falling blood glucose in diabetic subjects can occur despite elevated blood glucose levels. The etiology of norepinephrine and cortisol change is unclear.
A Simplified Method Using Somatostatin to Assess In Vivo Insulin Resistance over a Range of Obesity
Authors: Nagulesparan M , Savage Peter J , Unger Roger H , Bennett Peter H 
Published: September 2013

Twenty-one nondiabetic subjects, their weights ranging from 56 to 165 kg, received an infusion of glucose (420 mg/min), insulin (0.77 mU/kg/min), and somatostatin (500 figlh) for 150 min. A steady state level of plasma insulin and glucose was attained after 90 min. Endogenous insulin secretion, determined by C-peptide measurement, and glucagon secretion remained suppressed throughout the period. With similar steady state levels of plasma insulin (SSPI) maintained in all subjects, the height of the steady state plasma glucose concentration (SSPG) was considered an index of total body sensitivity to insulin-mediated glucose uptake. A positive correlation between SSPG and the degree of obesity, as determined by the body mass index (BMI), was demonstrated (r = 0.70, P &lt; 0.001). No correlation was found between SSPI and BMI. The fasting plasma insulin concentration correlated with BMI (r = 0.82, P &lt; 0.0001) and SSPG (r = 0.80, P &lt; 0.0001).
This method provides a simple safe measure of total body insulin resistance over a wide range of obesity and is independent of endogenous insulin secretion.
The Intravenous, Intraperitoneal, and Subcutaneous Routes of Insulin Delivery in Diabetic Man
Authors: Schade David S , Eaton R Philip , Friedman Neal , Spencer William 
Published: September 2013

Successful implantation of an artificial pancreas requires the infusion of insulin into an appropriate anatomic site. Three sites being actively investigated include (1) intravenous (i.V.), (2) intraperitoneal (i.p.), and (3) subcutaneous (s.c). This study compared the rate, magnitude, and duration of insulin absorption from these three absorption sites as assessed by the appearance of “free” insulin into the plasma of 10 insulin-dependent diabetic subjects. The biologic effectiveness of insulin was assessed by the suppression of plasma glucose concentration following a 750-calorie meal.
Our results suggest that i.v. delivered insulin provides the most rapid increase in plasma free insulin concentration, followed by the i.p. and s.c. routes, respectively. In contrast, the elevation of plasma free insulin concentration was most prolonged with the s.c. route, followed by i.p. and i.v. routes, respectively. Compared with the i.v. and s.c. routes of insulin delivery, only 50% of the i.p. delivered insulin appeared in the plasma. The onset of the biologic activity of the insulin delivered by the three different routes during the 4½-h observation period was most rapid for the i.v. and least rapid for the s.c. route. These results suggest that all three routes may be appropriate sites for delivery of insulin from an artificial pancreas. However, because of the difference in absorption kinetics and the onset of biologic effectiveness of the delivered insulin, different quantities and timing of insulin delivery may be needed.
Effectiveness of Insulin Therapy on Altered Renal Calcium Transport in Diabetic Rats
Authors: Hoskins Beth , Feibelman Richard Y , Koury Albert M , Taylor Ralph 
Published: September 2013

The uptake of 45Ca was measured in slices of kidney cortex from normal rats, streptozotocin-diabetic rats, and streptozotocin-diabetic rats treated early and late with insulin. Insulin therapy was performed such that blood glucose levels were controlled in half the treated diabetic animals but not in the others.
Considerably earlier than evidence of nephropathy (i.e., proteinuria and increased BUN levels) in streptozotocin-diabetic rats, there was a significant decrease in active uptake of calcium by the kidney. Insulin therapy, begun immediately upon diagnosis of diabetes, maintained normal calcium transport even when blood glucose levels were not controlled. On the other hand, insulin therapy, begun 1 mo after diabetes was confirmed but before evidence of nephropathy, did not restore calcium transport to normal whether or not blood glucose was controlled.
We conclude that this biochemical mechanism, which possibly may be implicated in the pathophysiology of diabetic nephropathy, is clearly influenced by duration of insulin deficiency and not by the degree in hyperglycemia.
Insulin Secretion and Cyclic Adenosine 3',5'-Monophosphate Levels in Pancreatic Islets of Fed and Fasted Rats: Time Course and Dose Kinetics During Glucose Stimulation
Authors: Bouman Paul R , Wolters Gerrit H J , Konijnendijk Willem 
Published: September 2013

Incubation of pancreatic islets of fed rats at glucose 10 and 15 mM induced a rapid rise of the islet cyclic adenosine 3',5'-monophosphate (cAMP) content. Maximum levels were attained at 15 min and lasted until 30 min, after which cAMP declined again. Insulin secretion increased most rapidly from 15 min onward, i.e. after the rapid rise of cAMP. Islet cAMP at either 15 or 30 min showed its major concentration-dependent increase between glucose 7.5 and 10 mM. Glucose 15 mM did not further enhance the cAMP response, although this concentration increased insulin secretion more than two-fold over values observed at glucose 10 mM. Thus, the glucose dose-response relations for cAMP levels and insulin secretion appear to be different, indicating that factors other than cAMP alone determine the secretory response to glucose.
Fasting for 24 and 72 h progressively inhibited glucose-induced insulin secretion. At glucose 15 mM the secretory inhibition disappeared after 30–45 min, but at glucose 10 mM it persisted for at least 90 min. Increasing periods of fasting also progressively delayed and inhibited the cAMP response to glucose, most strongly at glucose 10 mM. Fasting for 24 h shifted the glucose dose-response curves for cAMP and insulin secretion to the right, but the maximum responses at glucose 37.5 mM were not significantly inhibited. The secretory inhibition appeared to be linearly related with the cAMP content in two different ways: (a) At fixed concentrations of glucose, the increasing inhibition of the cAMP response (at 15 min) as induced by 24 and 72 h of fasting correlated with the secretory inhibition over the initial 30 min. (b) At one fixed period of fasting (24 h), the variable percent inhibition of the cAMP response to graded concentrations of glucose (5–37.5 mM) correlated with the percent secretory inhibition at these concentrations.
These correlations were no longer apparent after 30 min of incubation. The results support the view that inhibition of the adenylate cyclase-cAMP system is a major determinant factor in fasting-induced impairment of insulin secretion during the initial 30 min of glucose Stimulation.
Normalization of the Paradoxic Secretion of Glucagon in Diabetics Who Were Controlled by the Artificial Beta Cell
Authors: Shichiri Motoaki , Kawamori Ryuzo , Abe Hiroshi 
Published: September 2013

Since it is important to elucidate the precise significance of pancreatic A-cell hypersecretion in the pathogenesis of diabetes mellitus, the change in the immunoreactive glucagon (IRG) response to 100 g oral glucose challenges was studied in diabetics whose blood glucose responses and plasma immunoreactive insulin concentrations (IRI) simulated those in normal subjects with the aid of the artificial beta cell system that we developed originally.
In six nonobese adult-onset and four insulin-dependent diabetics whose blood glucose responses and plasma insulin concentrations after 100 g oral glucose load were made equivalent to those seen in normal subjects by the artificial beta cell, the glucagon release was similar to the response in normal subjects. In one insulin-dependent diabetic with high anti-insulin-binding capacity, the blood glucose response after an oral glucose challenge was not normalized by the artificial beta cell and the glucagon secretion was paradoxically increased. This fact suggested that the paradoxic rise in glucagon, seen in response to an oral glucose load in some diabetics, is secondary to insulin deficiency.
Impaired Cardiovascular Responses to Graded Exercise in Diabetic Autonomic Neuropathy
Authors: Hilsted Jannik , Galbo Henrik , Christensen Niels Juel 
Published: September 2013

Six juvenile diabetics [age, 31 ± 2 yr (mean and SEM); duration of diabetes, 15 ± 4 yr] with signs of autonomic neuropathy (decreased beat-to-beat variation in heart rate during deep breathing) and seven control patients of similar age (27 ± 1 yr) and duration of diabetes (14 ± 2 yr) performed graded exercise oh an ergometer cycle. Resting heart rate was higher and the increase in heart rate at the lowest work load (50 W) was diminished in patients with autonomic neuropathy compared with control patients (P &lt; 0.001), indicating a vagal defect.
The relationships in autonomic neuropathy between heart rate and systolic blood pressure, respectively, and relative work load (expressed as oxygen uptake — in percent—of individual maximal oxygen uptake) were identical with previous findings in normal subjects during beta-adrenergic receptor blockade, indicating impaired sympathetic activity. Maximal heart rate was 157 ± 9 min−1 in autonomic neuropathy and 181 ± 4 in controls, P &lt; 0.05; maximal systolic blood pressure was 179 ± 11 mm Hg and 197 ± 5, respectively.
The greatest tolerable work load was significantly less in patients with autonomic neuropathy (125 ± 13 vs. 161 ± 9 w, P &lt; 0.05). Similarly, maximal oxygen uptake was reduced (1.68 ± 0.21 vs. 2.78 ± 0.18 L/min, 25 ± 3 vs. 38 ± 2 ml/min/kg, P &lt; 0.005).
In conclusion, diabetics with decreased beat-to-beat variation in heart rate displayed signs of cardiovascular dysfunction of parasympathetic as well as sympathetic origin during graded exercise.
Glycemic Regulation Using a Programmed Insulin Delivery Device: III. Long-Term Studies on Diabetic Dogs
Authors: Goriya Yoshikazu , Bahoric Andrej , Marliss Errol B , Zinman Bernard , Albisser A Michael 
Published: September 2013

Long-term glycemic normalization in diabetic dogs has been achieved using a portable insulin delivery device. Six pancreatectomized male dogs carried the device for periods of 7 ± 2 (range –12) mo. Pulses of insulin were delivered every 90 s into the inferior vena cava through an exteriorized indwelling catheter In the postabsorptive period, insulin was infused at the mean rate of 0.44 ± 0.03 mU/min/kg and glycemia was 93 ± 7 mg/dl, while in the postprandial period insulin was infused for 7 h at the mean rate of 3.10 ± 0.22 mU/min/kg. A standard daily diet was provided, and the resulting glycemic profiles were similar to an age-, sex-, and weight-matched group of six healthy controls.
Peripheral insulin levels in the infused diabetic dogs (15 ± 1 μU/ml) were not significantly different from nondiabetic controls in the fasting state and were unresponsive to caloric provocation. However, in the postprandial period of enhanced delivery, insulin levels in the diabetic dogs were two to four times higher than in the controls.
Unaccountable episodes of hypo- or hyperglycemia did not occur. Techniques for long-term vascular access were developed such that catheter-related complications, including infection and thrombosis, were not encountered.
This study demonstrates the feasibility of long-term glycemic control in unrestrained diabetic animals using a preprogrammed waveform of insulin delivery. Hyperinsulinism accompanies the glycemic normalization when the hormone is delivered peripherally.
Correction of Ketosis by Suppression of Lipolysis with 5-Methylpyrazole-3-Carboxylic Acid in Rats with Established Diabetic Ketoacidosis
Authors: Axelrod Lloyd , Lloyd-Jones Peter , Martin Donald B 
Published: September 2013

Because the presence of an elevated plasma free fatty acid (FFA) concentration is not always sufficient to promote ketogenesis, we examined the contribution of circulating FFAs to ketogenesis in established diabetic ketoacidosis. We studied the effects of suppression of lipolysis on ketogenesis in rats with established streptozotocininduced diabetic ketoacidosis using 5-methylpyrazole-3-carboxylic acid (5-methylpyrazole) as an antilipolytic agent. In response to this substance, plasma FFA fell from 2.42 ± 0.15 meq/L to 0.56 ± 0.06 meq/L in four hours. There was a concomitant fall in total plasma ketone from 12.17 ± 0.60 mM to 2.62 ± 0.54 mM. The fall in total plasma ketone was due predominantly to a fall in the beta-hydroxybutyrate concentration but also to a fall in the acetoacetate concentration. Although the agent slowed the rise of plasma glucose in these diabetic animals, the concentration was markedly elevated (573 ± 22 mg/dl) at four hours.
Studies were performed in comparable rats with diabetic ketoacidosis to exclude the possibility that 5-methylpyrazole interferes with hepatic ketogenesis. When the plasma FFA concentration was raised by administration of a lipid emulsion and heparin (after plasma FFA and total plasma ketone had fallen in response to 5-methylpyrazole), total plasma ketone also rose despite the presence of 5-methylpyrazole. When the plasma FFA concentration was maintained at a high level by administration of a lipid emulsion and heparin from the start of the experiment, 5-methylpyrazole failed to affect the total plasma ketone concentration. Thus, availability of substrate (plasma FFAs) reversed or prevented the correction of ketosis by 5-methylpyrazole.
These findings indicate that circulating FFAs are rate limiting for the maintenance of the ketotic state in established diabetic ketoacidosis and support the view that the absence of ketosis in the usual patient with hyperosmolar nonketotic diabetic coma is a result of inadequate availability of plasma FFAs for ketogenesis. 5-Methylpyrazole converts an experimental model of diabetic ketoacidosis into one resembling hyperosmolar nonketotic diabetic coma.
Metabolic Control in Diabetic Patients: Effect of Insulin-secretory Reserve (Measured by Plasma C-Peptide Levels) and Circulating Insulin Antibodies
Authors: Gonen Boas , Goldman Jose , Baldwin David , Goldberg Ronald B , Ryan Will G , Blix Petra M , Schanzlin David , Fritz Karl J , Rubenstein Arthur H 
Published: September 2013

We measured circulating hemoglobin A1 (HbA1) and fasting plasma C-peptide concentrations in 100 diabetic patients. Pancreatic insulin reserve showed a negative correlation with HbA1 concentrations in nonobese, insulin-treated patients but not in obese patients, whether they were treated with insulin, oral agent, or diet alone. Patients with fasting C-peptide concentrations above 0.1 pmol/ml had significantly better metabolic control than did those with lower values.
Anti-insulin antibodies were measured in 37 patients. There was no correlation between metabolic control and the affinity constants or binding capacities of these antibodies.