bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulinotrophic Drugs: Effect on Intestinal Absorption of Sugar
Authors: Botros M , Selim R , Ghoneim Kh , Ghareeb A , Wahba N 
Published: December 2014

The effect of some insulinotrophic drugs on the transport of sugar was investigated in fasted, narcotized rats by continuous perfusion of cannulated long intestinal loops with galactose solution (18 mM.) circulated by air lift. Three consecutive perfusions (fifty minutes each) were performed in each rat, the drug being given in the second perfusion only. The rate of galactose disappearance was expressed as per cent of that in the first perfusion in the same rat.
Tolbutamide (50 mg./l kg. weight), glycodiazine (50 mg./l kg. weight), glisoxepid (BAY 4231, 2 mg./l kg. weight) and glibenclamide (0.25 mg./l kg. weight) were found to increase the rate of galactose disappearance in the second perfusion by 21 per cent, 5 per cent, 12 per cent and 25 per cent, respectively, and in the third perfusion by 21 per cent, 26 per cent, 32 per cent and 21 per cent, respectively, as compared to the rate in the corresponding perfusion of a control group. This increase was significant (P values &lt; 0.05) with all drugs in the second and third perfusions with the exception of glisoxepid in the second perfusion. These results are discussed in relation to the action of insulin and the effect of diabetes on intestinal absorption of sugars.
Observations on Lipolysis in Ketosis-resistant Growth-onset Diabetes
Authors: Hagroo Abdul A , Verma Narendra P S , Datta P , Ajmani Narinder K , Vaishnava Hari 
Published: December 2014

This study was undertaken to determine the mechanism of ketosis resistance, which is often observed among patients with growth-onset diabetes in the tropics. Lipolysis was tested in vivo in the ketosis-resistant patients with growth-onset diabetes by determining: (1) Plasma immunoreactive insulin (IRI), blood glucose, and serum free fatty acid (FFA) concentrations during tests with epinephrine, phentolamine and epinephrine, and propranolol and epinephrine in twenty-five patients; and (2) blood ketone bodies during epinephrine and propranolol and epinephrine tests in fifteen patients. The findings were compared with results obtained in a similar number of ketosis-prone subjects with growth-onset diabetes and twenty-two normal controls.
The mean fasting plasma IRI levels were significantly lower in the ketosis-resistant diabetics than in the normal subjects, although the fasting blood glucose levels were three and one-half times greater in these diabetics than in the controls. There was no significant change in the glucose and IRI levels during the three tests. Fasting serum FFA levels were significantly lower in the ketosis-resistant than those in the ketosis-prone diabetics. No detectable serum FFA response was observed in the ketosisresistant patients during any of the three tests. Blood ketone levels were comparable with the values obtained in the normal controls, but were significantly lower than those in the ketosisprone patients. Blood ketones also did not change significantly during epinephrine and propranolol with epinephrine tests in the ketosis-resistant patients.
These results are interpreted to indicate that the mobilization of FFA from the adipose tissue is inadequate in the growth-onset diabetics who are ketosis resistant. The tailure is attributed to insensitivity of the adrenergic receptor sites and/or unresponsiveness of the adenyl cyclase-cyclic AMP-lipase system in the adipose tissue of these young diabetics. The absence of ketonemia in these diabetics is attributable to an insufficient delivery of the substrate (FFA) from the adipose tissue to the liver.
Homeostasis of Body Weight in a Diabetes Clinic Population
Authors: Goodner Charles J , Ogilvie James T 
Published: December 2014

Body weights, blood glucose concentration, and therapeutic and clinical data were summarized by computer for each patient visit to our diabetes clinic between 1965 and 1970. Homeostasis of body weight was examined by plotting regression of body weight on time for patients making five or more visits to the clinic during the study period. A similar analysis was made of blood glucose values. Data from 131 patients treated with oral agents or by dietary regulation alone and forty-one patients treated with insulin were analyzed. Precision of regulation was assessed by calculating the coefficient of variation of body weight while the trend of body weight was assessed by calculating the slope of the linear regression equation relating body weight and time.
In both treatment groups the individual slopes for body weight clustered closely around zero and the mean slopes did not differ significantly from zero. The coefficient of variation of body weight was also small, averaging 4.6 and 3.7 per cent of body weight in the oral agent and insulin treatment groups respectively. In contrast, blood glucose fluctuated widely in the two groups. Mean slopes for glucose versus time did not differ significantly from zero, however.
The remarkable stability of body weight in this diabetic population despite widely varying modes of therapy, glucose concentrations, and degrees of body adiposity suggests that signals controlling long-term feeding behavior are either not related to these variables or, more likely, are multiple and sufficiently redundant to permit adaptation to perturbations of several metabolic variables.
Effects of Hypoglycemic Sulfonamides on Glucagon and Insulin Secretion in Ducks and Dogs
Authors: Kajinuma Hiroshi , Kuzuya Takeshi , Ide Takehiko 
Published: December 2014

Infusions of tolbutamide (1 mg./kg. min.), glibenclamide (2.5 μg./kg. min.), or glymidine Na (1 mg./kg. min.) in ducks produced a prompt fall in plasma immunoreactive glucagon (IRG), a prompt rise in plasma immunoreactive insulin (IRI) and a subsequent fall in plasma glucose. In dogs, the infusions of these three sulfonamide drugs also caused a rise in IRI and subsequent hypoglycemia, but no specific changes in IRG level in the pancreatic vein and the femoral artery. The infusion of glibenclamide (0.013 μg./kg. min.) into the pancreatic artery of a dog increased IRI secretion and produced a fall in plasma glucose but did not affect IRG level in the pancreatic vein. Carboxytolbutamide, which lacks hypoglycemic activity, failed to influence IRG and IRI in ducks.
The results suggest that the hypoglycemic effect of sulfonamide drugs is mediated by insulin release and, in ducks but not in dogs, by suppression of glucagon secretion. The cause of this species difference is unknown, but the present results and additional data suggest that ducks may be much more dependent than dogs on glucagon for carbohydrate metabolism.
Abnormalities of Myocardial Depolarization in Overt, Subclinical and Prediabetes: A Vectorcardiographic Study
Authors: Riff Emmanuel R , Riff Kenneth M 
Published: December 2014

Vectorcardiograms were performed on fifteen diabetic patients, and all were found to have either the vectorcardiographic criteria for myocardial infarction or “bites.”
Twenty adults with normal fasting blood sugars and not known to be diabetics were found to have bites; eleven (55 per cent) had an abnormal glucose tolerance test; four of the remaining nine were tested further and three (75 per cent) had an abnormal cortisone glucose tolerance test.
Four apparently normal children, age four to twelve, from two families were studied. In both families, the mother had insulindependent diabetes and the father had subclinical diabetes. All four children had vectorcardiographic abnormalities.
This pilot study indicates that if the vectorcardiographic criteria for myocardial damage are correct, then it exists at an earlier stage in diabetes than has previously been recognized. Alternatively, if a morphologic abnormality cannot be demonstrated then a physiologic explanation must be advanced to account for these vectorcardiographic abnormalities.
Decrease and Inhibition of Liver Glycogen Phosphorylase After Fructose: An Experimental Model for the Study of Hereditary Fructose Intolerance
Authors: Thurston Jean Holowach , Jones Elizabeth M , Hauhart Richard E 
Published: December 2014

Inhibition of liver phosphorylase may play an important role in the fructose-induced hypoglycemia of hereditary fructose intolerance. This report is an in vivo study of the effects of fructose on selected metabolic intermediates and on phosphorylase activity in the liyers of young mice. Phosphorylase activity in liver homogenate was measured in the direction of glycogen breakdown. The Km for Pi was 1.12 mM and the Ki for fructose-1-phosphate was 1.19 mM. This finding is particularly relevant since twenty minutes after fructose injection (30 mmoles per kilogram intraperitoneally) liver Pi was reduced 50 per cent, p &lt; 0.001 and fructose-1-phosphate was increased fifty fold, p &lt; 0.001. Liver glucose was unchanged.
In controls, activity of phosphorylase was dependent on the state of the animals: 2.43 ± 0.31 μ/moles/gm. min−1 in anesthetized mice, 9.55 ± 0.55 in excited animals. Under these same conditions phosphorylase activity in fructose-injected littermates was reduced 40 to 80 per cent (mean 48 per cent, p = 0.002). At the concentrations of Pi and fructose-1-phosphate found in liver after fructose, phosphorylase activity in vitro was inhibited 88 per cent (p &lt; 0.001). In vivo the activity of liver phosphorylase is apparently reduced by two mechanisms, a conversion to the inactive form and an inhibition of the remaining active enzyme by reduced Pi and elevated fructose-1-phosphate levels. We have postulated that de novo synthesis of glucose from fructose in normal animals could mask any hypoglycemia which might result from reduced liver phosphorylase activity.
The in vivo effect of glucose injection on liver phosphorylase was also studied. At high levels of enzyme activity, glucose reduced phosphorylase activity by 43 per cent, p = 0.012; at low levels of enzyme activity, glucose had no effect.
Role of Insulin and Glucagon in Obesity
Authors: Schade D S , Eaton R Philip 
Published: December 2014

To investigate the hormonal balance in obesity with respect to insulin and glucagon secretion and to assess their effect at the substrate level, we compared ten obese subjects with an equal number of normal weight controls. No subject was diabetic by USPHS criteria.
Aminogenic hormonal secretion was measured after arginine was given intravenously at a rate of 1 gm.'min. for thirty minutes. Changes in the hormonally sensitive substrates, glucose and free fatty acids, were examined in relation to the hormonal secretion.
Our obese population was characterized by increased insulin and decreased glucagon secretion. At the substrate level, these hormonal differences were reflected in changes of serum glucose but not in free fatty acids.
Phytohemagglutinin Transformation and Circulating Lymphocyte Subpopulations in Insulin-dependent Diabetic Patients
Authors: MacCuish A C , Urbaniak S J , Campbell C J , Duncan L J P , Irvine W J 
Published: December 2014

The lymphocyte transformation response to the mitogen phytohemagglutinin (PHA) was determined in forty well controlled insulin-dependent diabetics, forty matched normal subjects and fourteen poorly controlled insulin-dependent diabetics. There was no significant difference in the PHA responses of normal subjects and well controlled diabetics, but poorly controlled diabetics showed a marked depression of lymphocyte transformation.
Peripheral blood T and B lymphocyte subpopulations were also measured in fifteen normal subjects, fifteen well controlled diabetics and ten poorly controlled diabetics. The results showed no significant difference between normal and diabetic subjects, whether well or poorly controlled.
The depressed PHA response in poorly controlled diabetics would seem to reflect inadequately corrected metabolic disturbance rather than an inherent, genetically determined immunologic abnormality.
Prevention of Vascular Disease in the Diabetic
Authors: Kinsell Laurance W 
Published: December 2014

In view of the present state of our knowledge, the title of this paper is ambitious. I may begin with the unequivocal statement that neither my associates nor I have any magic formula which predictably will prevent vascular disease in the diabetic. However, I should like to consider with you some of the observations of others, and some observations of our own which bear upon this subject.
In our own thinking, diabetes mellitus is divided into two diseases: the form that occurs typically in middle age, which, from a functional standpoint, we consider as presenting essentially a problem in hypoinsulinism with associated metabolic abnormalities; and juvenile diabetes, which represents a combined problem of hyperpituitarism and hypoinsulinism.
In both groups one deals with two vascular problems. One, atherosclerosis, is identical with that which afflicts the average nondiabetic member of the American population, if he lives sufficiently long. Statistically, the onset of this vascular disease in the diabetic is earlier and the progress more rapid. The other is a rather specific disease, in which characteristic changes occur in the retinal and glomerular capillaries. This latter problem is most distressing in the juvenile diabetic, because of its occurrence at an early age.
Atherosclerosis in Association With Diabetes With the possible exception of cancer, no field of clinical investigation is receiving more attention than that of degenerative vascular disease. Since atherosclerosis in the diabetic appears earlier and progresses more rapidly than in the nondiabetic, and since we have some knowledge of the endocrine and metabolic abnormalities which occur in diabetes and which, at least in part, are presumably related to the pathogenesis of the vascular disease, it seems logical to conclude that the answer to the over-all problem of atherosclerosis might very well be found more readily in the diabetic than in the nondiabetic population.
The Distribution and Metabolism of Insulin Labeled with Radioactive Iodine (I131) in Normal and Diabetic Subjects
Authors: Welsh George W , Henley Elaine D , Williams Robert H , Elgee Neil J 
Published: December 2014

To investigate possible differences in the distribution and metabolism of insulin in diabetics and normals, insulin labeled with radioactive iodine (I131) was given intravenously to 40 diabetics of varying type and severity, 15 healthy controls, and 11 other nondiabetics with various illnesses. The labeled insulin was given in tracer amounts (50 to 100 microcuries) and test doses varied between 0.5 and 5.0 units of insulin. The dose was diluted in normal physiologic saline solution and injected slowly into fasting subjects over a two-minute period. In most cases therapeutic insulin had been withheld from diabetics for 24 to 96 hours. Plasma samples were drawn at predetermined times, and the amount of protein-bound radioactivity was determined by precipitation with trichloroacetic acid (TCA).
Since labeled insulin is virtually completely precipitated with TCA, the protein-bound radioactivity was assumed to represent undegraded labeled insulin, whereas the TCA-soluble radioactivity was assumed to be comprised of the degradation products of the labeled hormone. Total urinary radioactivity, of which an average of 95 per cent is TCA-soluble, was also measured during the test period. In some subjects surface measurement of radioactivity over various organ areas, such as the thyroid, liver, kidney, and muscle masses, was made.
The Prediabetic State in Man: Definition, Interpretation and Implications
Authors: Conn Jerome W 
Published: December 2014

It is with pride, humility and a sense of important responsibility that I begin the presentation of a Banting Memorial Lecture.
The problem which I have chosen to discuss today is one with which my group has been concerned during the past eleven years. It has to do with the effect of ACTH and glucocorticoids upon carbohydrate tolerance of normal people. Before proceeding further I wish to point out that today I act as spokesman for the various past and present members of my research staff who have contributed their ideas and efforts to this long-term project.
Diabetes Mellitus and Its Degenerative Complications: A Prospective Study of 4,400 Patients Observed Between 1947 and 1973
Authors: Pirart Jean 
Published: December 2014

This article was originally published in French in Diabete et Metabolisme (vol. 3: 97–107, 173–182, 245–256; 1977). The Editors of DIABETES CARE thank the author, and the editors and publisher of Diabete et Metabolisme for granting permission for us to print this English translation. The paper was translated by Marjorie Levin of Miami, Florida.
Part 2 of this translation will appear in the July–August issue of DIABETES CARE.
Subcutaneous Glucagon-Like Peptide I Combined With Insulin Normalizes Postcibal Glycemic Excursions in IDDM
Authors: Dupré John , Behme Margaret T , Hramiak Irene M , Mcdonald Thomas J 
Published: December 2014

OBJECTIVE
To determine whether a subcutaneous injection of truncated glucagon-like peptide 1 (tGLP-I)(7–36) amide that delays gastric emptying transiently can prevent postcibal hyperglycemia in IDDM without causing hypoglycemia when administered with insulin.

RESEARCH DESIGN AND METHODS
The postcibal increase in plasma human pancreatic polypeptide (HPP) was used as a presumptive indicator of arrival of nutrient in the small intestine. Studies in seven normal human volunteers established the dose of tGLP-I that delayed the postcibal rise in HPP by 30 min. This dose was tested in six patients with IDDM with a range of residual endogenous insulin secretion. The patients received a standard liquid test meal with or without subcutaneous tGLP-I and their usual dose of regular insulin before the meal. Blood samples collected at timed intervals were assayed for plasma concentrations of glucose, C-peptide (CP), immunoreactive insulin (IR1), HPP, and glucagon (GLN).

RESULTS
In normal subjects after administration of tGLP-I, postcibal plasma glucose concentration at 20 min fell below fasting levels in a dose-dependent manner. At 10 and 20 min, transient increments in plasma CP and IRI, and decrements in GLN, occurred. Subsequently, through 60 min, the excursions of plasma HPP, CP, and IRI were negatively correlated to the dose of tGLP-I. In subjects with IDDM, the selected dose of tGLP-I given with insulin before the meal delayed the plasma HPP response for 30 min and confined excursions of plasma glucose within the range observed in normal subjects receiving saline injections, whereas administration of insulin with saline injections in IDDM was followed by supranormal increases of plasma glucose. In IDDM, this dose of subcutaneous tGLP-I had no effect on plasma CP, IRI, or GLN.

CONCLUSIONS
In normal subjects, transient hypoglycemia after injections of tGLP-I with a meal was associated with transient stimulation of insulin secretion and inhibition of glucagon secretion. These actions together with delayed gastric emptying may account for the hypoglycemia, but other unidentified mechanisms cannot be excluded. In the subjects with IDDM, the selected relatively low dose of tGLP-I delayed excursions of plasma HPP as in normal subjects, but did not reduce the plasma glucose below the fasting level and had no effect on plasma CP, IRI, or GLN. However, injection of tGLP-I reduced the postcibal glycemic excursion and confined it within the normal range. Thus, in IDDM, a pharmacological dose of subcutaneous tGLP-I that presumably delays gastric emptying by ∼30 min can normalize glycemic excursions after a meal when given in combination with insulin. Because this cannot be achieved with regular insulin alone without risk of hypoglycemia, this combination of glucoregulatory peptides has therapeutic potential in insulin-requiring diabetes.
A Portable System for Continuous Intravenous Insulin Delivery: Characteristics and Results in Diabetic Patients
Authors: Hanna Amir K , Mlnuk Howard L , Albisser A Michael , Marliss Errol B , Leibel Bernard S , Zinman Bernard 
Published: December 2014

A portable insulin delivery system for clinical use has been developed, with the aim of improving glycemic control for prolonged periods for individuals with insulin-dependent diabetes. It weighs 1.5 kg and measures 8 × 11 × 20 cm. A plastic case contains two insulin reservoirs, two peristaltic pumps (flow variability ± 3%), a battery pack, and voltage regulator. Silastic tubes connect the reservoirs to an indwelling intravenous catheter inserted into the arm. The system is carried by a strap over the shoulder. One pump operates continuously, giving insulin at a “basal” rate, and the other is activated during meals to give a preprogrammed waveform of insulin, the latter controlled by a small bedside unit.
Twelve insulin-dependent diabetic patients were infused with insulin by this system for 4–60 days (mean 18 days), for a total of 199 patient days. Insulin delivery rates were modified according to data obtained by intermittent glycemic monitoring, and on one and in some cases two days glycemia was continuously monitored (N = 10). With a basal infusion rate of 18 ± 2 mU/min (mean ± SEM), fasting glycemia was 99 ± 7 mg/dl.
The mean insulin delivered with meals was 12 ± 2 U for breakfast, 9 ± 2 U for lunch, and 11 ± 2 U for dinner. Mean glycemia before lunch and supper was 102 ± 6 and 121 ± 11 mg/dl, respectively. The lowest mean glycemia occurred after lunch (88 ± 7 mg/dl) and the mean peak postprandial glycemia was 136 ± 8 mg/dl (2 h after supper). The range from lowest to highest observed value was 47–189 mg/dl. This system is capable of maintaining glycemia within the normal range for periods up to 60 days. Further refinement of the waveforms of insulin delivery may allow for total glycemic normalization. The future refinement of such a system will allow for longer-term studies addressing the relationship between glycemic control and complications.
The Peritoneum — A Potential Insulin Delivery Route for a Mechanical Pancreas
Authors: Schade David S , Eaton Philip 
Published: December 2014

The potential advantages of the peritoneum as an insulin delivery site for an implanted mechanical pancreas are reviewed. During embryogenesis in humans, the development of the pancreas and liver are closely related such that, in the adult, all endogenous insulin secreted by the pancreas passes directly to the liver before entering the peripheral circulation. This anatomic relationship permits the direct modulation of absorbed nutrients from the gut by both the liver and pancreatic hormones. Preliminary studies in the dog indicate that at least a portion of insulin infused into the peritoneal space enters the hepatic portal vein before entering the peripheral circulation, thereby simulating normal pancreatic insulin secretion.
Infusion of insulin directly into the peritoneum in humans has demonstrated that (1) insulin absorption is rapid (within minutes), (2) it results in appropriate meal-related peaks in peripheral insulin concentration, and (3) the insulin has biologic activity in suppressing meal-induced hyperglycemia. Furthermore, analysis of the absorbed insulin pattern indicates that approximately 50% of the delivered insulin is removed before entering the peripheral circulation, compatible with hepatic insulin removal. In addition, insulin delivered into the peritoneum in diabetic individuals may result in a reduction in meal-related glycemic excursions, compared with a similar quantity of NPH insulin delivered subcutaneously. Thus, the peritoneum may be a rational alternative to both the intravenous and subcutaneous delivery sites for an implanted insulin delivery system,