bluuebunny/crossref_metadata_2025 huggingface dataset:
Editorial
Authors: Clark David J
Published: September 2013

The story of Res Medica has been one of success, so far. The Journal was started only two years ago and has prospered enormously. The people responsible for this success are undoubtedly the members of the first Editorial Committee. Our role has been simply to add fuel to the fire which their enthusiasm set alight. Thus, during its second year, the Journal's circulation has doubled. The size has grown considerably, and we are financially stable. It has been our aim to base Res Medica on the Society's public business and as many as possible of our Addresses, Talks, and Dissertations are now included. We hope that future editors will follow this policy.In the present issue we include a most fascinating article by Professor Swann. In those long past lectures to us in our first year, he expressed complicated ideas in a minimum of words. He has a knack of using a short word where others might use a long one, of using one word where others might employ two. Consequently his lectures are stimulating and intelligible even for those whose education has not included any biological study. His article reminds us of this talent and provides us with much to think about. It is easy to see why he was so delighted to obtain that electron microscope.
Family Medicine
Authors: Scott Richard
Published: September 2013

The Faculty of Medicine of this University has decided that from now onwards every student shall be provided with the means of not only observing, but of actively participating in, the provision of medical care for patients in their own homes. The task of making the necessary arrangements is the responsibility of the University's General Practice Teaching Unit. It gives me particular pleasure to accept an invitation from the Royal Medical Society to contribute to its journal an article on this Unit, its history, aims, philosophy, and teaching methods.
The Diagnosis of Chest Disease
Authors: Turner J H
Published: September 2013

This is not an article on the latest means available for the diagnosis of chest diseases, but simply a consideration of history taking and of signs and symptoms. Medicine is without meaning unless we think in terms of patients. It is by developing our powers of observation and interpretation while we are in contact with our patients that we learn medicine, rather than from books and articles.Hippocrates is our great master of the art of inspection-he stands for the fundamental importance of seeing clearly. To-day if we read his reports of 2,400 years ago we can often make an almost instantaneous diagnosis. Descriptions which cannot be bettered are the squeaking of leather for a pleural friction rub, or the boiling inside the chest of pulmonary oedema. In the time of Hippocrates as much as now thoroughness in examination produces more correct diagnoses than sudden flashes of brilliance.
Electrolyte Imbalance
Authors: Dudley H A F
Published: September 2013

The subject of this paper is Electrolyte Imbalance. Unqualified, such a title may sound like an overambitious attempt to embrace within the span of forty-five minutes the whole gamut of the disordered physiology of the anions and cations. Mindful of the penalty of such vaulting ambition which would, I think, without doubt "fall on the other" its content will be limited largely to some of the more acute and dramatic examples of disturbances of body fluid that are commonly encountered in surgical patients. Surgery deals with the sort of patients of whom John Donne might well have been thinking when he said "this minute I was well and I am ill this minute " and consequently the pattern of electrolyte imbalance encountered by the surgeon is usually drawn in starker and bolder lines than is the more subtle, long drawn out problem with which the physician is often confronted. This makes life considerably easier for the surgeon who is not uncommonly a simple man of action rather than a profound thinker; an extrovert rather than an introvert, a Roman rather than a Greek. Therefore, this account is mainly from a surgeon's point of view with an occasional digression.
Rockets, Men and Medicine
Authors: Crombie A L
Published: September 2013

Space Medicine has at last become an accepted entity in the vast field of medical research after many years of ridicule and scorn. The recent successes of the U .S.S.R. and U .S.A. in launching earth and sun satellites would seem adequate to justify the existence of space medicine. It seems Man's avowed intention to conquer the third dimension, the vertical, which leads to space and as such it is the duty of the medical scientist to make this journey as safe as possible for the would-be space traveller.Space is not a well defined region since it has no accurate topographical boundaries and in the context of this article the best way of defining space is to think in terms of levels of space equivalency, i.e. levels at which various protective functions of the Earth's atmosphere are lost so creating a space-like state for a certain phenomenon at a particular altitude. From the viewpoint of respiratory physiology space begins at a height of 52,500 feet since the effects of explosive decompression assume a constant value at and over this level. In similar terms the atmosphere acts as a filter against cosmic factors and this function of itself provides a variety of space equivalencies ranging from sea level in the case of infra-red rays, to 10-20 miles for cosmic primaries and as high as 75 miles for visible light. Space, therefore, is a concept which of necessity is a variable and its effects may be just as varied.
Twenty-Four-Hour Serum Growth Hormone Levels in Maturity-Onset Diabetics
Authors: Kjeldsen Henning , Hansen Aage Prange , Lundbaek Knud
Published: September 2013

Serum growth hormone, glucose, and insulin were studied every half hour during a twenty-four-hour period of “daily life” in four groups of subjects: nonobese normal subjects, obese normal subjects, nonobese maturity-onset diabetics, and obese maturity-onset diabetics.

It was found that (1) serum growth horomone was uniformly low without meal- and sleep-related peaks in obese normals and diabetics. The twenty-four-hour serum growth hormone level was significantly higher in nonobese subjects than in obese subjects, in both diabetics and normals; (2) the twenty-four-hour serum growth hormone level was more fluctuating and significantly higher in nonobese diabetics than in nonobese normals; (3) there was no difference in the twenty-four-hour serum growth hormone level between obese diabetics and obese normals.
Insulin Secretion in the Spiny Mouse (Acomys Cahirinus): Dose and Time Kinetic Studies with Glucose in Vivo and in Vitro
Authors: Rabinovitch Alexander , Gutzeit Arndt , Renold Albert E , Cerasi Erol
Published: September 2013

Plasma insulin responses to the intravenous injection of glucose in the doses of 0.5, 1.5, and 3.0 gm./kg. were compared in spiny mice (Acomys cahirinus) and weight-matched Swiss albino mice. The mean early (two-minute) plasma insulin response was significantly lower in Acomys at all doses of glucose injected; whereas, at later times (5, 15, and 30 minutes), differences in plasma insulin concentrations in the two species of mice were smaller or nonexistent. Plasma glucose clearance was significantly less in the Acomys. In terms of glucose dose kinetics, there was a decreased capacity of the mean plasma insulin response in Acomys compared with albino mice at two minutes; whereas, at later times, the mean dose response curve for Acomys was shifted to the right of that for albino mice, indicating a decreased sensitivity to glucose in the Acomys. There was, however, a large variation between the plasma insulin responses of the eight individual Acomys mice tested. There was a significant correlation in individual Acomys between the plasma insulin response, expressed as an insulinogenic index, integrated over the thirty minutes after injection of glucose 3.0 gm./kg. in vivo, and the insulin released from pancreatic islets obtained from the corresponding Acomys and perifused for thirty minutes with glucose 1,000 mg./100 ml. in vitro (r = 0.77, p < 0.05). It is concluded that the rate and magnitude of the insulin response to glucose in an individual Acomys reflects mainly the degree of sensitivity to glucose of the pancreatic beta cells in that animal.
Comparison of the Lipolytic Effects of Insulin and Proinsulin on Isolated Fat Cells
Authors: Lavis Victor R , Williams Robert H
Published: September 2013

Proinsulin, like insulin, has a biphasic effect on the lipolysis of isolated fat cells. Low concentrations of the peptides inhibit the response to submaximal doses of epinephrine, while higher concentrations of the peptides enhance the effect of supramaximal doses of epinephrine. Half-maximal doses are: (a) inhibition of lipolysis: insulin, 2.3 × 10−11M; proinsulin, 6.9 × 10−10M; (b) enhancement of lipolysis: insulin, 3.1 × 10−9M; proinsulin, 8.1 × 10−8M. The ratios of the potencies of the peptides are the same for both effects. These results suggest that both the inhibitory and the lipolytic effects of insulin are not caused by contaminants, and are mediated by similar receptors.
Relationship Between Serum Chromium Concentrations and Glucose Utilization in Normal and Infected Subjects
Authors: Pekarek R S , Hauer E C , Rayfield E J , Wannemacher R W , Beisel William R
Published: September 2013

Studies in healthy individuals demonstrate that serum chromium concentrations fall precipitously following the intravenous administration of a 30-gm. glucose load. Significant decreases from baseline control fasting serum Cr concentrations were also observed when intravenous glucose was given during sandfly fever. Glucose disappearance rates also decreased significantly to approximately one half of pre-illness control values while serum Cr values declined still further. In addition, serum Cr disappearance rates could be calculated. When individual preexposure and postexposure serum glucose and Cr disappearance rates were compared, a significant linear correlation was found (P <0.05). Acute infection appears to reduce the availability of circulating Cr, which may contribute to the altered glucose metabolism characteristic of acute infections even in the presence of elevated insulin levels and other hormonal changes.
Calcium Antagonists and Islet Function: I. Inhibition of Insulin Release by Verapamil
Authors: Devis G , Somers G , Van Obberghen E , Malaisse W J
Published: September 2013

Verapamil is a potent calcium antagonist known to inhibit excitation-contraction coupling in both myocardium and myometrium. Its effect upon glucose- and sulfonylurea-induced insulin release was investigated in the isolated perfused rat pancreas.

After twenty-five minutes' pretreatment and at concentrations ranging between 0.8 and 8.1 μM, verapamil caused a dose-related inhibition of glucose-induced insulin release during both the early and late phase of the secretory process. At a concentration of 0.8 μM, the degree of inhibition was more marked when the exposure time to verapamil prior to stimulation with glucose was increased to sixty minutes. Verapamil also inhibited gliclazide-induced insulin release. Infusion of verapamil during the late phase of the secretory response to glucose demonstrated that the inhibition of insulin release was an immediate and reversible phenomenon. The inhibitory effect of verapamil was enhanced at a subnormal calcium concentration and reduced at a high calcium concentration.

These findings are consistent with the well-known calcium dependency of both glucose- and sulfonylurea-induced insulin release and suggest that verapamil might be a promising tool for further studies on the interactions between cations and secretagogues in the β-cell secretory process.
Insulin-like Insulinase-resistant Material, Distinguishable from Normal Insulin, in Juvenile Diabetes
Authors: Crossley Jeanette R , Elliott R B
Published: September 2013

This study compares some properties of the immunoreactive insulin-like material extracted from the urine of children with overt diabetes with that from normal children. Insulin-like species were fractionated by gel filtration and by isoelectric focusing and were tested for sensitivity to an insulin-specific degradative enzyme. Insulin concentration was measured by radioimmunoassay. The major insulin-like component from the urine of ten normal children and fifteen untreated juvenile diabetics and from the urine of four and the serum of one latent diabetics behaved (on gel filtration) as normal insulin, was sensitive to insulinase, and (in all cases studied) had an identical isoelectric point (resolution 0.1 pH units).

A proportion of the immunoreactivity extracted from urine (0–4 per cent from normal children, 5–30 per cent from twelve of the thirteen nonobese untreated diabetic children) eluted from the gel filtration column before insulin. This material from diabetic urine was of two size classes, “proinsulin-like” and “mid-insulin,” both resistant to degradation by insulinase. Insulinase-resistant immunoreactivity from one patient was analyzed by isoelectric focusing. Urine samples from two obese children with overt diabetes and four children with latent diabetes contained normal proportions (less than 4 per cent) of immunoreactive species larger than insulin. The possible nature and significance of the present insulinaseresistant species are briefly considered.
Insulin Receptors in the Heart Muscle: Demonstration of Specific Binding Sites and Impairment of Insulin Binding in the Plasma Membrane of the Obese Hyperglycemic Mouse
Authors: Forgue Marie-Elisabeth , Freychet Pierre
Published: September 2013

The presence of insulin receptors in the heart muscle was investigated by measuring the binding of 125I-insulin to specific subcellular fractions of the rat and mouse myocardium. 125I-insulin bound to the plasma membrane fraction with a high degree of specificity and affinity. Insulin analogues competed with 125I-insulin in direct proportion to their biologic potency in vitro. Unlabeled insulin within the range of its concentrations in vivo inhibited 15 to 60 per cent of the 125I-insulin binding. The specific binding-sites were finite in number and represented about 90 per cent of the total binding. The insulin-binding capacity of the plasma membrane fraction was twelve- to fifteenfold higher than that of the mitochondrial fraction. As in the liver, the binding was time- and temperature-dependent with a slower but higher binding achieved at a lower temperature. The binding sites appeared to be heterogeneous with respect to affinity. At 5° C , the “higheraffinity” site had a K of about 2 × 109 M−1. No more than 10 percent of the 125I-insulin was degraded by the heart plasma membranes after one hour at 30° C. or twenty-two hours at 5° C.

Studies in the obese hyperglycemic (ob/ob) mouse revealed that the insulin binding is impaired in the heart muscle of this animal. Over a wide range of insulin concentrations, the plasma membrane fraction of ob/ob mice bound only 25 to 40 per cent as much insulin as did membranes of the thin littermates, suggesting that, as in the liver, the fat tissue, and the thymic lymphocyte, the number of insulin-binding sites is decreased in the heart of the ob/ob mouse. This defect selectively affected the plasma membrane fraction and could not be explained by differences in membrane purification or in insulin-degrading activity. Heart and liver membranes of fortyhour fasted ob/ob mice bound two to three times as much insulin as did membranes of ob/ob mice fed ad libitum.

These studies demonstrate and characterize the binding of insulin to heart muscle membranes; they extend to the heart muscle the insulin receptor defect also found in liver membranes and cells, in fat cell membranes, and in thymic lymphocytes of the ob/ob mouse.
Comparison of 125I-Insulin Binding and Degradation to Isolated Rat Hepatocytes and Liver Membranes
Authors: Olefsky Jerrold M , Johnson Jennifer , Liu Francis , Edwards Peter , Baur Sonia
Published: September 2013

We have compared the ability of rat liver plasma membranes and isolated hepatocytes to bind and degrade insulin. Isolated cells were prepared in two different ways: by mechanical separation of cells and by coliagenase digestion of extracellular matrix. In all studies the binding and degradative characteristics of both types of hepatocyte preparations were identical. Furthermore, with one exception, the binding characteristics of membranes and cells were also quite similar. The only exception concerned the amount of insulin bound by hepatocytes as compared to liver membranes. Thus, at concentrations of cells (1.2 × 106 cells per milliliter) and membranes (150 µg. protein per milliliter) that gave equal binding at insulin concentrations <100 ng./ml., the amount of insulin specifically bound at insulin concentrations >100 ng./ml. was greater with use of hepatocytes. Additional studies indicated that, in contrast to membranes, at the higher insulin concentration only 75 percent of the previously bound insulin could be recovered from hepatocytes. Thus, a nondissociable component exists, which probably represents intracellular radioactivity and appears to account for the higher specific insulin binding by cells at higher insulin concentrations. When insulin degradation was studied at the above hepatocyte and plasma membrane concentrations, cells degraded 30 per cent more insulin than did membranes. Kinetic analysis of these data revealed that the Km for insulin degradation (5 × 10−7 M at 37°) was the same for both systems whereas the Vmax was greater with use of hepatocytes. In conclusion: (1) Preparation of hepatocytes by coliagenase digestion does not appear to alter insulin binding or degradation; (2) studies of liver membranes and isolated hepatocytes obtained from normal rats should yield similar information about insulin-receptor interaction as long as insulin concentrations <100 ng./ml. are used; (3) at very high insulin concentrations, some of the radioactivity appears to enter the cells; (4) the kinetics of insulin degradation by hepatocytes and liver membranes are similar; and (5) insulin degradation appears to be primarily a membrane phenomenon.
Hyperinsulinemia and Hyperglucagonemia Following Pancreatic Islet Transplantation in Diabetic Rats
Authors: Weber C J , Hardy M A , Lerner R L , Felig P , Reemtsma K
Published: September 2013

Fasting blood glucose (FBG), serum immunoreactive insulin (IRI), plasma immunoreactive glucagon (IRG), body weight, and caloric intake were measured in long-term islet-isografted rats eight to 10 months following intraperitoneal islet transplantation in in age-matched, sham-operated, concurrently followed normal and diabetic controls. Islet recipients had normal body weights, but they were significantly polyphagic, hyperinsulinemic, and hyperglucagonemic when compared with normals. Fasting blood glucose levels were reduced by 10 per cent. Several factors may be related to the occurrence of these abnormalities in long-term islet-isografted rats, including (1) the mass of islets transplanted, (2) the age of donor tissue, (3) the heterotopic location of islet grafts, and (4) the lack of normal innervation of transplanted islet cells.
Abnormal Carbohydrate Metabolism in Amyotrophic Lateral Sclerosis and Parkinsonism-dementia on Guam
Authors: Koerner Donald R
Published: September 2013

Amyotrophic lateral sclerosis and Parkinsonism-dementia are unusually prevalent on Guam. Carbohydrate metabolism was studied in 110 patients with evidence diagnostic of or suspecious for these diseases. The combined incidence of known diabetes in 29 per cent of them plus a high percentage of glucose tolerance tests interpreted as abnormal, even when most age-related criteria were considered, was considerably higher than the incidence of abnormal carbohydrate metabolism reported elsewhere in the general population of the United States, the tropical Pacific area, or in recent surveys on Guam itself. The diabetes was generally mild in nature and noteworthy for a lack of retinopathy and other complications. Hypertension, hypercholesterolemia, and hyperuricemia, although highly prevalent, were not consistently associated with abnormal glucose metabolism. Similarly, no consistent association was demonstrated with such factors as age, muscle atrophy, or physical activity.
Early Detection of Diabetic Visceral Neuropathy: An Electrophysiologic Study of Bladder and Urethral Innervation
Authors: Andersen Jens T , Bradley William E
Published: September 2013

The segmental and supraspinal innervation of the detrusor muscle and periurethral striated musculature was studied in 27 patients with diabetes mellitus by gas cystometry, integrated sphincter electromyography, and spinal evoked-response latency measurements. Slowing of neural conduction velocities was a consistent finding in all the patients, even when cystometry did not show abnormalities. Thus, neuropathy in the segmental innervation of the bladder and urethra was documented.
Growth of Rabbit Aortic Smooth-Muscle Cells Cultured in Media Containing Diabetic and Hyperlipemic Serum
Authors: Ledet Thomas , Dzoga Katti Fischer , Wissler Rober W
Published: September 2013

Smooth-muscle cell cultures were grown from thoracic aortas of normal and diabetic rabbits. The effect of diabetic rabbit serum on the growth of these cultures was studied both in the first, rapid-growth phase and the following, more “stationary” phase of growth. Control experiments were carried out on normal sera to which glucose had been added. The concentrations of cholesterol, phospholipid, and triglyceride were same in both normal and diabetic sera.

Media containing diabetic serum stimulated the growth of cultures significantly in both phases (2p < 0.01). This occurred in experiments utilizing cells from normal as well as from diabetic rabbits. Control media containing normal serum with added glucose had no such effect. The growth-promoting effects of diabetic serum and of hyperlipemic serum from nondiabetic rabbits were of the same order of magnitude.

Autoradiographic studies showed that the number of 3H-thymidine-labeled cells increased significantly after culture in diabetic serum (2p < 0.005).

Cells cultured from the very beginning in diabetic serum or normal serum with added glucose were significantly larger than cells grown in control serum (2p < 0.05 and 2p < 0.01, respectively). Cells grown in hyperlipemic serum were significantly smaller than those grown in normal serum (2p < 0.01).

These results indicate that diabetic serum contains a factor or factors that stimulate the arterial medial cell to excessive growth. This factor is not glucose, insulin, or lipid. The results may be of relevance for the understanding of human diabetic macroangiopathy.
Effect of Somatostatin on Blood Sugar, Plasma Growth Hormone, and Glucagon Levels in Diabetic Children
Authors: Guercio M J Del , Natale B di , Gargantini L , Garlaschi C , Chiumello G
Published: September 2013

In nine children with clinically overt insulin-dependent diabetes mellitus the authors injected cyclic somatostatin (3 mug./kg. bolus, followed by infusion of 13 mug./kg. in 60 minutes) and measured blood glucose, plasma growth hormone, and glucagon concentrations throughout the infusion. The rapid administration produced no significant changes of these parameters. With the prolonged infusion there was a significant reduction of blood glucose from a mean of 148 ± 19.7 to a mean of 88.5 ± 18.1 mg./100 ml. (P < 0.005) and of plasma glucagon from a basal mean of 33.3 ± 2.4 to a minimum mean of 22.1 ± 1.7 pg./ml. (P < 0.01). There was a statistically significant correlation between the two parameters (0.01 < P < 0.05). Plasma GH values also diminished during the infusion, but the reduction was not statistically significant.

These results show that somatostatin lowers blood glucose concentrations as a secondary effect of inhibition of glucagon secretion. Somatostatin is not suitable for therapy in diabetes. We speculate that a similar substance with a more prolonged and specific action on glucagon might prove of practical value in the treatment of diabetes mellitus.
Carbohydrate Metabolism and Capillary Basement-membrane Thickness in Children: II. Longitudinal Studies
Authors: Sheikholislam Bagher M , Irias Julian J , Lowrey George H , Lin Hung-Jung
Published: September 2013

Longitudinal biochemical and histologic studies were carried out in 11 children receiving oral hypoglycemic agents. There were five “suspected” diabetics (with evidence of glucose intolerance but without repeated fasting hyperglycemia) and six diabetics.

Mean fasting plasma glucose (FPG) values showed no significant change during treatment with phenformin alone. The mean FPG decreased significantly within six to 10 weeks after addition of tolazamide to the regimen, but the decrease was not sustained during long-term observation (seven months to four years). Glucose disappearance rate (K) generally increased as FPG decreased, but the number of observations was smaller, and mean values showed no significant change. Mean values for fasting plasma insulin and for peak insulin response to intravenously administered glucose did not change significantly.

Changes in capillary basement-membrane thickness (BMT) were found to be statistically significant in a number of individual instances. Decreasing BMTs were associated with increasing Ks and vice versa. A similar trend was apparent among other patients, in whom individual changes in BMT were not statistically significant. The pooled data were therefore subjected to chi-square analysis; K and average BMT were found to change in opposite directions (P < 0.001); a similar relationship held for K and minimum BMT (P < 0.05). But K and BMT did not correlate well as regards magnitude of change. Influences of phenformin and tolazamide on these changes could not be evaluated.

Both BMT and K may be influenced by many complex variables, but the present findings indicate that glucose tolerance and BMT have a close interdependence.
Histocompatibility Antigens and Diabetic Retinopathy
Authors: Becker Bernard , Shin Dong H , Burgess Dean , Kilo Charles , Miller William V
Published: September 2013

Of 160 patients with onset of diabetes at or after 30 years of age, the 84 with no evidence of diabetic retinopathy were found to have significantly increased prevalences of HLA-Al and B8 when compared with the 76 with retinal complications or with the 282 healthy blood donors. In addition, in 90 patients with onset of diabetes before age 30 years, we could confirm the reported significant increase of HLA-B8 and decrease of B7, but no differences were noted between those juvenile-onset diabetics with and those without retinopathy.
Serum Insulin Response to Slow-rise Glucose Infusion in “Genetic Prediabetics” (Offspring of Two Diabetic Parents)
Authors: Tan M H , Williams R F , Soeldner J S , Gleason R E
Published: September 2013

The insulin response to a programed slow-rise glucose infusion designed to mimic the postprandial rise in glucose was studied in five offspring of two diabetic parents (ODP) and seven normal subjects. The ODP had higher mean blood glucose levels towards the end of the infusion and during the postinfusion period. The rates of glucose disappearance calculated during the postinfusion period were comparable in the two groups. Despite the apparent similarity of serum insulin levels of ODP and normal subjects, the amount of insulin secreted per unit of glycemie stimulus was lower in the ODP group. When the glucose infusion test was preceded by an acute load of glucose, similar findings in the insulin secretory dynamics were found in the ODP group. These data suggest that an impairment in insulin secretion exists in ODP when they are challenged by the slow rise of blood glucose achieved by this type of an intravenous glucose infusion.
Insulin Binding in Diabetes: Relationships with Plasma Insulin Levels and Insulin Sensitivity
Authors: Olefsky Jerrold M , Reaven Gerald M
Published: September 2013

Insulin binding to isolated circulating monocytes from normal subjects and adult patients with diabetes was studied. The diabetic subjects were nonketotic, and their degree of glucose intolerance varied from an abnormal oral glucose tolerance test (chemical diabetes) to significant fasting hyperglycemia. The results indicated that patients with chemical diabetes had a 45 per cent decrease in insulin binding to monocytes, and this decrease was secondary to a reduction in the number of receptor sites per cell (normals, 15,000 sites per monocyte versus 8,500 sites per mono-cyte for chemical diabetics). When the individual data from the normal and chemical diabetic subjects were examined, a highly significant inverse correlation was found between the amount of insulin bound and both the fasting plasma insulin level (r = 0.61, P > 0.001) and the incremental insulin area during an oral glucose tolerance test (r = 0.49, P > 0.001). Furthermore, insulin binding was closely and inversely correlated to the degree of insulin resistance (r = 0.65, P > 0.001) among these subjects. Thus, the ability to bind insulin is inversely related to both the plasma insulin level and insulin sensitivity, and chemical diabetics who are insulin-resistant and hyperinsulinemic have a decreased ability to bind insulin. Many patients with fasting hyperglycemia also have decreased insulin binding. However, although as a group these pa tients have fasting hyperinsulinemia, they are hypoinsulinemic in response to a glucose challenge. Thus, inclusion of their data with that of the normal and chemical-diabetic patients enhances the relationship between insulin binding and fasting insulin level (r = 0.68, P > 0.001) but obliterates the relationship between insulin binding and incremental insulin area. Furthermore, in these subjects no significant correlation was found between insulin binding and the degree of insulin resistance (r = 0.19, N.S.), suggesting that all or most of the insulin resistance in these subjects was independent of changes in insulin receptors. In conclusion, (1) if the subjects are taken as a group, in patients with chemical diabetes and in diabetic patients with fasting hyperglycemia, insulin binding to monocytes is decreased; (2) over the entire spectrum of adult, nonketotic diabetes, insulin binding is decreased to monocytes from patients with fasting hyperinsulinemia, while subjects with normal insulin levels have normal insulin binding; (3) the insulin resistance of patients with chemical diabetes may be related to a decrease in insulin receptors, but this does not appear to be the case for patients with fasting hyperglycemia; and (4) plasma insulin levels are inversely related to insulin binding, but it is the basal, not the stimulated levels that are associated with changes in insulin receptors.
Hypothalamic Regulation of Insulin Release in Rhesus Monkeys
Authors: Hill Donald E , Mayes Susan , DiBattista David , Lockhart-Ewart Robin , Martin Julio M
Published: September 2013

Evidence of a neurohumoral factor capable of stimulating insulin and glucagon secretion was found in perfusates from ventrolateral hypothalamus (VLH) of rhesus monkeys. The perfusates from the VLH were collected via push-pull cannulas and injected into the peripheral circulation. Increase in portal insulin and glucagon was observed following the injection of six different perfusates. The amount of insulin released from isolated rat islets incubated with perfusates was significantly increased at glucose concentrations > 5 mM. The perfusates from the VLH appear to have effects on insulin and glucagon secretion that are opposite those of somatostatin.
Magnesium Metabolism in Experimental Diabetes Mellitus
Authors: Fort Pavel , Lifshitz Fima , Wapnir Irene L , Wapnir Raul A
Published: September 2013

One of the consequences of uncontrolled diabetes mellitus (DM) is an increased urinary loss of magnesium. Some of the factors determining this electrolyte imbalance were studied in growing rats with experimentally induced DM. Two sets of experiments were performed in which dietary magnesium intake was the variable. One group each of diabetic (DB) and control (C) animals was fed a complete diet including magnesium ad libitum; the other set was given the same diet as the first two groups but the magnesium was provided daily through a stomach tube in amounts equal to those eaten by non-DB rats of the same size. All DB animals had significantly higher than normal urinary excretion of glucose, magnesium, calcium, and phosphorus. There was a positive correlation between urinary glucose and magnesium excretion. DB animals fed magnesium ad libitum became hypomagnesemic, but their bone magnesium content was increased over that of C rats. Plasma magnesium correlated negatively with both glucose and cholesterol. However, alterations in plasma cholesterol induced in C rats by dietary means had no effect on magnesium levels. When magnesium intake was restricted to the physiologic requirements of C animals, hypomagnesemia was more pronounced and occurred with concomitant depletion of magnesium in bone, suggesting possible risk of electrolyte imbalance in uncontrolled DM. The results indicate that hypomagnesemia without osseous tissue magnesium depletion may occur in experimental DM. Hyperphagia in DB animals fed ad libitum can prevent bone magnesium depletion, but a “normal” intake that does not compensate for losses may be conducive to a marked deficit in the intracellular pool of magnesium.
Vascular Lesions Associated with Impotence in Diabetic and Nondiabetic Arterial Occlusive Disease
Authors: Herman Aryeh , Adar Raphael , Rubinstein Zalman
Published: September 2013

Translumbar aortographies performed in 91 patients for limiting leg ischemia were reviewed, and stenosis was graded by points from one (normal vessel) to five (complete occlusion) for each vessel. Of 62 nondiabetic patients, 18 (29 per cent) were impotent, while of 29 diabetics, 17 (58.6 per cent) were impotent (p < 0.01). Significantly greater stenosis (p < 0.005) was found in the internal pudendal arteries of impotent patients when compared statistically with potent patients. This was true for the group as a whole, for diabetics and nondiabetics, and for patients over 50 years old both with and without diabetes. There was no significant difference in the extent of stenosis of the iliac arteries (common and internal) between potent and impotent patients. There was also no significant difference in the pattern of stenosis between diabetic and nondiabetic patients in the group as a whole and also in the potent and impotent subgroups analyzed separately. Neither diminished femoral pulses nor aortographic evidence of external iliac and common femoral arterial stenosis correlated significantly with impotence.

These observations indicate that vascular lesions are as important in diabetics as in nondiabetics in the genesis of impotence. Clinical implications regarding diagnostic investigations and treatment are discussed.
Influence of Maturity-onset Diabetes on Splanchnic Glucose Balance After Oral Glucose Ingestion
Authors: Felig Philip , Wahren John , Hendler Rosa
Published: September 2013

To determine the extent to which altered splanchnic glucose balance contributes to postprandial hyperglycemie in diabetes, splanchnic glucose exchange was determined in seven maturity-onset diabetics and 10 healthy control subjects in the basal state and for three hours following oral ingestion of 100 gm. of glucose.

In the basal fasting state, arterial glucose levels in the diabetics (153±24 mg./100 ml.) were 75 to 80 mg./100 ml. higher than in controls while splanchnic glucose output was similar in the two groups (132 to 145 mg. per minute). Following glucose ingestion, arterial glucose concentration in the diabetics rose to peak levels (295 ±35 mg./100 ml.) that were 55 per cent higher than in controls and remained 100 to 125 mg./100 ml. above basal levels and 150 to 200 mg./100 ml. above control levels three hours after glucose. Splanchnic glucose output rose rapidly in the diabetics to values four times the basal rate at 15 to 30 minutes after glucose feeding and remained 60 per cent or more above basal levels throughout the three-hour period. In contrast, in the controls following a similar early rise, splanchnic glucose output returned to basal levels by 90 minutes. As a consequence, total splanchnic glucose output over three hours in the diabetics (53±4 gm.) was 33 per cent greater than in controls. In addition, the increment in splanchnic glucose output above basal levels in the diabetics (30±5 gm.) was 100 per cent greater than in controls and could account for 75 per cent of the augmented glucose accumulation in body fluids observed at three hours.

It is concluded that in maturity-onset diabetics (1) net splanchnic glucose output is increased after glucose ingestion, suggesting that a greater proportion of an oral glucose load enters the systemic circulation than in healthy controls; (2) failure of splanchnic glucose retention is the major factor responsible for postprandial hyperglycémie in maturity-onset diabetes.
Glucose-stimulated 45Ca Uptake in Isolated Rat Islets
Authors: Frankel Barbara J , Kromhout John A , Landahl Herbert D , Grodsky Gerold M
Published: September 2013

Net 45Ca uptake (in excess of the extracellular 3H-sucrose space) and insulin release were measured under low (2 mM) and high (20 mM) glucose conditions in collagenase-isolated rat islets. 45Ca uptake curves were mathematically fitted and subjected to compartmental analysis.

Within the first 60 seconds after addition of trace 45Ca, islets showed a similar rapid uptake of 45Ca regardless of the glucose concentration or length of time of prior exposure to glucose. Net 45Ca uptake continued to increase for 30-60 minutes, and the islets in high glucose showed approximately twofold greater maximum uptake than islets in low glucose. Islets preincubated in low glucose and then incubated in high glucose showed a 5-15-minute delay in net 45Ca uptake as compared with islets that had been preincubated in high glucose.

Insulin release was detectable by 10 minutes of incubation with high glucose.

Mathematical modeling of the low- and high-glucose net 45Ca uptake curves suggests that there are at least two calcium “compartments” within the β-cell. One compartment is small, rapidly filled, and insensitive to glucose, while the other, larger compartment, is slowly filled and fills to a much greater extent in the presence of high glucose. A major proportion of the glucose-stimulated uptake is at the level of influx.
Amino Acid Stimulation of Glucagon Secretion by Perifused Islets of High-protein-fed Rats
Authors: Eisenstein Albert B , Strack Inge
Published: September 2013

Feeding of a high-protein, carbohydrate-free (HP) diet to rats results in elevated plasma glucagon and increased glucagon secretion by isolated islets of Langerhans. Since amino acids liberated during protein digestion may cause increased pancreatic glucagon release, the effects of 21 amino acids on glucagon secretion by perifused islets of HP-fed and control rats were examined. Arginine caused a marked rise of glucagon secretion, which consisted of an initial burst followed by a sustained phase of elevated hormone release. Total glucagon secretion by HP islets in response to arginine was 69.8 ± 5.3 pg./islet/30 minutes and by control islets was 30.0 ± 2.6, P = <0.001. Perifused islets responded physiologically to suppression as well as stimulation, since the arginine effect was abolished by raising the medium glucose level to 16.7 mM or by addition of small amounts of somatostatin (10 ng./ml). Of the 10 essential amino acids, only arginine had a major effect on hormone release by the alpha cell. Glutamine and α-aminobutyrate caused increases of glucagon secretion that were similar in pattern and magnitude to that induced by arginine. Total glucagon secretion by HP islets in response to glutamine was 65.6 ±4.6 pg./islet/30 minutes and by control islets was 39.1 ±8.1. Glucagon release by HP islets in response to α-aminobutyrate was 63.4 ± 4.6 pg./islet/30 minutes. Ornithine caused a sharp rise of glucagon release that was not sustained. Total hormone secretion induced by ornithine amounted to 27.3 ±6.9 pg./islet/30 minutes. None of the other nonessential amino acids, including alanine, had a major effect on pancreatic alpha cell function.
Effect of Atropine on Glucose-stimulated Gastric Inhibitory Polypeptide
Authors: Larrimer John N , Mazzaferri Ernest L , Cataland Samuel , Mekhjian Hagop S
Published: September 2013

Gastrointestinal augmentation of insulin secretion observed in response to glucose ingestion may be largely mediated by gastric inhibitory polypeptide (GIP). Since the enteric signal potentiating insulin secretion is blunted by atropine, we studied the effects of this drug on glucose-stimulated GIP secretion in normal subjects. Eight individuals, studied on two occasions, were given intraduodenal glucose (75 gm. over 60 minutes) by perfusion tube, on one occasion with intravenous atropine (15 μg. per kilogram bolus followed by 17 μg. per minute for 60 minutes) and on another occasion with intravenous saline (control). Comparing the results of atropine and control studies, mean serum immunoreactive GIP (IRGIP) was significantly lower at 5 and 15 minutes (444 ± 82 vs. 277 ± 44, p < 0.05 and 1,072 ± 151 vs. 427 ± 74 pg./ml., p < 0.02 at 5 and 15 minutes, respectively), and the integrated incremental area under the 120-minute curve was significantly less (62,170 ± 11,880 vs. 91,820 ± 14,200 pg. ·minute·ml.−1 p < 0.05) with atropine. Serum IRI levels were also significantly lower during the atropine studies (28 ± 8 vs. 14 ± 2, p < 0.05, 54 ± 7 vs. 25 ± 5, p < 0.02, 62 ± 8 vs. 36 ± 7 μU. per milliliter, p < 0.05, at 15, 30, and 45 minutes, respectively). The integrated incremental area under the IRGIP curve was reduced about 33 per cent, while the area under the IRI curve was reduced about 45 per cent by atropine. In a second group of similar experiments substituting d-xylose for glucose, the effect of atropine on d-xylose absorption was studied in normal subjects. Atropine did not alter d-xylose absorption during the first hour, but significantly enhanced its absorption during the second hour, as compared with control studies. We conclude that atropine blunts the rise in serum IRGIP normally stimulated by intestinal glucose perfusion, which is probably a direct effect of the drug on the gastrointestinal tract, as opposed to an effect mediated by inhibition of glucose absorption. These observations are consistent with the hypothesis that GIP is the enteric signal potentiating insulin secretion that is attenuated by atropine.
Forearm Hemodynamics and Responses to Exercise in Middle-aged Adult-onset Diabetic Patients
Authors: Katz Murray A , Janjan Nora
Published: September 2013

Much of the difficulty in assessing the progress of diabetic angiopathy and effects of experimental modes of therapy arises from the lack of quick, simple, inexpensive, and noninvasive tests to perform on the circulatory system of human subjects. We report here on values obtained by the use of mercury-in-rubber strain gauge plethysmography on 15 middle-aged, adult-onset diabetics who had minimal clinical evidence of microangiopathy. Standard tests are described for assessing forearm vascular function at rest, during tonic exercise of the fingers, and after interrupted repetitive exercise of the fingers. When matched against a similar aged nondiabetic group, the diabetics had slightly higher forearm vascular resistance at each level of exercise, a marked reduction (∼ 50 per cent) in capillary filtration coefficient, which is believed to be related to vascular filtering surface area, and a slight reduction in venous capacitance at all levels of exercise. The method of mercury-in-rubber strain gauge venous occlusion plethysmography provides the clinician with a sensitive and inexpensive tool with which to follow the evolution of angiopathy in diabetic patients.
Low Density Lipoprotein Receptor Activity in Fibroblasts Cultured from Diabetic Donors
Authors: Chait Alan , Bierman Edwin L , Albers John J
Published: September 2013

Low density lipoprotein (LDL) receptor activity was evaluated in cultured skin fibroblasts from diabetics and nondiabetic controls to evaluate whether intrinsic abnormalities of the LDL pathway exist, which might account for the premature atherosclerosis associated with diabetes mellitus. LDL receptors did not differ between cells grown from 16 diabetics (7 insulin-dependent, 9 non-insulin-dependent) or from 16 nondiabetic controls. An inverse relationship between LDL receptor activity and cell density was observed (y = 1.35 × −1.22, r = 0.90, P < 0.001), which appeared the same for diabetic and nondiabetic cells. Normalized values for LDL degradation by diabetic and nondiabetic cell strains were 1.52 ± 0.42% of added LDL/106 cells and 1.34 ± 0.28, respectively (P = NS). The kinetics of the LDL receptor also appeared to be the same in cells derived from a diabetic and a nondiabetic donor. LDL receptor activity in diabetic cells increased appropriately in response to physiologic concentrations of insulin in the incubation medium.

Thus, LDL receptor activity appears to be normal in diabetic cell strains. Therefore, these results do not support the possibility that alterations in the LDL pathway contribute to the accelerated atherosclerosis associated with diabetes.
A Study of Glucagonomas by Light and Electron Microscopy and Immunofluorescence
Authors: Bordi Cesare , Ravazzola Mariella , Baetens Dany , Gorden Phillip , Unger Roger H , Orci Lelio
Published: September 2013

Five tumors associated with the complete glucagonoma syndrome, as well as a series of glucagon-cell adenomas from three patients without this syndrome, were investigated by light and electron microscopy and by immunofluorescence.

All tumors associated with the syndrome were large, from 3 to 35 cm along the major axis, and three of them were proved to be malignant. No common histologic arrangement of tumor cells was apparent for the five neoplasms examined. Immunofluorescent staining for glucagon and glicentin was carried out: while most cells were negative, a varying number of scattered cells were positive with both antisera in all tumors except one; three tumors contained more glicentin- than glucagon-immunoreactive cells. Moreover, three tumors were multihormonal, with cells positive for pancreatic polypeptide and/or insulin. Ultrastruc-turally, the secretory granules of cells from these tumors were not typical of those found in A-cells from adult human islets.

The glucagon-cell tumors from patients without the syndrome were benign, usually multiple, and were small, with diameters from 0.5 mm to 1 cm. In most cases, the cells from these neoplasms arranged in a characteristic pattern (ribbonlike or “gyriform”). In most tumors, the majority of cells showed both glucagon and glicentin immunofluorescence and the ultra-structural appearance of their secretory granules was similar to that of normal islet A-cells. From the morphologic point of view, therefore, cells from tumors not associated with the glucagonoma syndrome resemble normal glucagon cells more closely than those from tumors associated with the syndrome.
Spontaneous Diabetes in the Gnotobiotic BB/W Rat
Authors: Rossini Aldo A , Williams R Michael , Mordes John P , Appel Michael C , Like Arthur A
Published: September 2013

To determine the influence of infectious agents on the initiation of diabetes in the spontaneously diabetic Bio-Breeding/Worcester (BB/W) rat, susceptible rats were raised in a germ-free environment. Between 2 and 3 mo of age, 3 of 12 pups became diabetic. Histologic examination of the pancreas revealed insulitis or end-stage islets. Culture and smears from various tissues were negative for bacteria or parasites. Serum vital antibody titers for all known rat viruses were undetectable. These data suggest that the diabetic syndrome of the BB/W rat is not dependent on recognized infectious agents.