bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum Proinsulin in Children and Adolescents with Chemical Diabetes
Authors: Rosenbloom A L , Starr J I , Juhn D , Rubenstein A H
Published: September 2013

Proinsulin levels (PLC) in serum were determined after gel filtration on specimens obtained during oral glucose tolerance testing (OGTT) in seven patients with repeated abnormality in OGTT and in a group of seven control subjects matched for age. Fasting and thirty-, sixty-, and 120-minute postglucose venous samples were analyzed for glucose (PG) and immunoreactive insulin (IRI) as well as PLC. PG and IRI mean concentrations were greater at all testing times in the patient population, but the mean IRI/PG was significantly higher in the patients only at fasting. PLC mean levels were higher in the patients but not to a level of significance. Percentage of total IRI attributable to PLC at each time point was identical between the two groups. The apparent diminished effectiveness of circulating insulin in chemical diabetes cannot be attributed to an abnormal proportion of proinsulin.
Discordance of Diabetic Microangiopathy in Identical Twins
Authors: Karam J H , Rosenthal M , O'Donnell J J , Tsalikian E , Lorenzi M , Gerich J E , Siperstein M D , Forsham P H
Published: September 2013

In a pair of 19-year-old monozygotic twin girls, one developed insulin-dependent, ketosis-prone diabetes at the age of three and has required insulin for the past 16 years. Her identical twin has maintained normal oral and intravenous glucose tolerance with normal insulin release and glucagon suppression. An unequivocal hypertrophy of the muscle capillary basement membrane(1,800 ± 148 Å) was found in the diabetic twin, while a normal thickness of 1,149 ± 62 Å was present in her nondiabetic sister. Follow-up of the present subjects and data from other discordant identical twins who have reached adulthood could determine whether muscle capillary basement membrane hypertrophy is an independent marker of genetic diabetes in adults.

Discordance of diabetic microangiopathy in a pair of monozygotic twins has important implications regarding the influence of heredity and environment on diabetic microangiopathy.
Blood Glucose Monitoring in Symptomatic Hypoglycemia
Authors: Cole Richard A , Benedict G William , Margolis Simeon , Kowarski Avinoam
Published: September 2013

The relationship between blood glucose levels and the onset of hypoglycemic symptoms was studied by continuous monitoring of blood glucose levels after an oral glucose load in nine adults with normal glucose tolerance, five with chemical diabetes without symptomatic hypoglycemia, and nine with chemical diabetes with symptomatic hypoglycemia. Symptoms were associated not only with a low level of blood glucose but with a rapid fall as well. These two parameters were used to calculate a “hypoglycemic index” (defined as the fall in blood glucose during a 90-minute period prior to reaching the minimum level, divided by the value of this minimum level). The hypoglycemic index was 2.3 ± 0.6 (mean ± S.D.) in the group of diabetic patients with symptomatic reactive hypoglycemia and 0.7 ± 0.3 for the other groups. This index may aid in the diagnosis of patients with symptoms of hypoglycemia and equivocally low values of blood glucose.
Leucocyte-migration Inhibition Induced by Uveoretinal Antigen in Patients with Diabetic Retinopathy
Authors: Aviner Zvi , Henley Walter L , Okas Sirje , Leopold Irving H
Published: September 2013

Leucocyte-migration inhibition was to determine the state of hypersensitivity in 65 diabetic patients with different stages of retinopathy and 21 nondiabetic controls. About one third of the patients with simple or proliferative retinopathy exhibited significant leucocyte-migration inhibition of 0.2 mg./ml. protein concentration of uvreoretinal antigen. In contrast, only one of 15 patients with minimal retinopathy and none of the controls showed significant leucocyte-migration inhibition. Corneal and lenticular antigens did not evoke a cellular immune response in any of the tested individuals. These findings suggest that cell-mediated hypersensitivity to uveoretinal antigen may develop in diabetic patients with prolonged, progressive, simple or proliferative retinopathy.
Cerebral Edema Complicating Therapy for Diabetic Ketoacidosis
Authors: Duck Stephen C , Weldon Virginia V , Pagliara Aanthony S , Haymond Morey W
Published: September 2013

Four cases of cerebral edema associated with therapy for diabetic ketoacidosis are reported. One patient had an inappropriate ADH-like syndrome at the time of onset of clinical symptoms of cerebral edema; he survived. The remaining patients had hyponatremia at or near the time of onset of clinical symptoms of cerebral edema, and they subsequently died. The literature is reviewed and some aspects of therapy, which might be casually related to cerebral edema observed in association with therapy of diabetic ketoacidosis, are discussed.
Neuroendocrine Control of Insulin Secretion
Authors: Lockhart-Ewart Robin B , Mok Ching , Martin Julio M
Published: September 2013

The effects of thyrotropin-releasing hormone, luteinizing hormone-releasing hormone, substance P, somatostatin, and a partially purified hypothalamic extract on insulin secretion were tested both in vitro and in vivo. Only somatostatin and the hypothalamic extract affected insulin secretion. In vitro, somatostatin decreased glucose-stimulated insulin secretion by isolated islets and in vivo significantly reduced the rate of insulin output into the portal vein. The hypothalamic extract significantly stimulated insulin secretion in both systems. These effects in vivo were independent of glucose concentration. Islets preincubated for four hours responded better in vitro to the hypothalamic extract stimulation and the somatostatin inhibition.
Effect of Insulin on the Exaggerated Glucagon Response to Arginine Stimulation in Diabetes Mellitus
Authors: Raskin Philip , Aydin Ismet , Unger Roger H
Published: September 2013

The effect of insulin on the glucagon response to intravenous arginine was studied in eight juvenile-type and six adult-onset diabetics. In the juvenile-type diabetics, concomitant administration of insulin significantly blunted the glucagon response from a mean maximal rise of 310 ± 54 pg./ml. to only 184 ± 39 pg./ml. (p < 0.01), about the same as in nondiabetics. In the adult-onset patients, however, insulin had no effect, the mean maximal rise being 250 ± 50 pg./ml. without insulin and 307 ± 71 pg./ml. with insulin (N.S.).

This study demonstrates that in juvenile-type diabetics concomitant administration of supraphysiologic quantities of insulin can reduce the exaggerated glucagon response to intravenous arginine to normal, whereas in the adult-type group, it has no apparent effect.
Glucagon Secretion from the Perfused Pancreas of Streptozotocin-treated Rats
Authors: Weir Gordon C , Knowlton Stephen D , Atkins Robert F , McKennan Kevin X , Martin Donald B
Published: September 2013

One hour following intravenous streptozotocin, rat pancreases were perfused in situ, and , in contrast to saline-injected controls a marked decrease of insulin secretion was observed. In these streptozotocin-treated animals, baseline glucagon secretion was enhanced when the perfusate glucose concentration was either 80 mg./100 ml. or 300 mg./100 ml. In addition there was hypersecretion of glucagon in response to arginine.

Exogenous insulin (20,000 μU./ml.) could suppress glucagon secretion when endogenous secretion was plentiful. Baseline and arginine-stimulated glucagon secretion of the streptozotocin treated animals was not suppressed by large amounts of glucose and insulin to the degree seen in control animals. The glucagon rise in response to an abrupt fall of glucose from 80 mg./100 ml. to 25 mg./100 ml. was not significantly higher in the control group than in the streptozotocin group.

The results seen with epinephrine were in sharp contrast to those found with arginine. Epinephrine-stimulated glucagon secretion was not enhanced in the streptozotocin group. In addition, epinephrine-induced secretion could be suppressed by exogenous insulin in both the control and streptozotocin groups. The differences may be secondary to differences of endogenous insulin secretion.

The present results are compatible with the hypothesis that local insulin secretion can exert a significant suppressive effect upon the alpha cell and that the inhibition of glucagon secretion by glucose is partially mediated by this mechanism. Furthermore, anomalous local insulin secretion may contribute to the abnormal glucagon secretion of diabetes mellitus.
Differential Sensitivity of Glycogenolysis and Gluconeogenesis to Insulin Infusions in Dogs
Authors: Chiasson J L , Liljenquist J E , Finger F E , Lacy W W
Published: September 2013

The suppressive effect of insulin on hepatic glucose production is generally recognized. Though it is well established that this effect is at least partially due to inhibition of glycogenolysis, controversy still exists about insulin's effect on gluconeogenesis. The present study was undertaken to determine whether insulin could affect gluconeogenesis from alanine in the intact dog and to compare the effect of insulin on glycogenolysis and gluconeogenesis.

In anesthetized dogs fasted overnight, blood samples were drawn simultaneously from a femoral artery and hepatic vein. Alanine-U-14C, 10 μCi./kg., was infused over 110 minutes. A constant insulin infusion at either 1 or 5 mU./kg./min. was begun at 50 minutes, and blood glucose concentration was maintained by a variable glucose infusion. When insulin was infused at 1 mU./kg./min., resulting in plasma immunoreactive insulin (IRI) levels of 73 ± 10 μU./ml., the net splanchnic glucose production (NSGP) was suppressed from 2.7 ± 2 mg./kg./min. to virtually zero. In constrast, this small increment in insulin concentration had no demonstrable effect on the net splanchnic uptake of alanine or on the conversion of plasma alanine to glucose (7.9 ± 0.3 μmol/min.). Insulin infused at 5 mU./kg./min. resulted in IRI levels of 240 ± 25 muU./ml. This higher insulin concentration was associated with a marked suppression of both the NSGP (100 per cent) and the conversion of plasma alanine to glucose (90 per cent) but did not affect the extraction of alanine by the splanchnic bed. Doses of both 1 and 5 mU./kg./min. were associated with a 35 per cent fall in immunoreactive glucagon levels.

These data demonstrate that (1) glycogenolysis is more sensitive than gluconeogenesis to the inhibitory effect of small increments in insulin concentrations, (2) gluconeogenesis could be suppressed by insulin but only at higher insulin concentrations, (3) this suppression of gluconeogenesis from alanine by insulin was due to an intrahepatic effect rather than an effect on the splanchnic extraction of alanine, and finally, (4) that insulin can suppress glucagon in the absence of hyperglycemia.
Quality, Efficiency, and Cost of a Physician-Assistant-Protocol System for Managment of Diabetes and Hypertension
Authors: Komaroff Anthony L , Flatley Margare , Browne Christina , Sherman Herbert , Fineberg S Edwin , Knopp Robert H
Published: September 2013

Briefly trained physicians assistants using protocols (clinical algorithms) for diabetes, hypertension, and related chronic arteriosclerotic and hypertensive heart disease abstrated information from the medical record and obtained history and physical examination data on every patient-visit to a city hospital chronic disease clinic over a 18-month period. The care rendered by the protocol system was compared with care rendered by a “traditional” system in the same clinic in which physicians delegated few clinical tasks.

Increased thoroughness in collecting clinical data in the protocol system led to an increase in the recognition of new pathology. Outcome criteria reflected equivalent quality of care in both groups. Efficiency time-motion studies demonstrated a 20 per cent saving in physician time with the protocol system. Coct estimates, based on the time spent with patients by various providers and on the laboratory-test-ordering patterns, demonstrated equivalent costs of the two systems, given optimal staffing patterns. Laboratory tests were a major element of the cost of patient care,and the clinical yield per unit cost of different tests varied widely.
Suppression and Stimulation Mechanisms Controlling Glucagon Secretion in a Case of Islet-Cell Tumor Producing Glucagon, Insulin, and Gastrin
Authors: Tiengo Antonio , Fedele Domenico , Marchiori Elisa , Nosadini Romano , Muggeo Michele
Published: September 2013

The mechanisms controlling secretion of glucagon and other pancreatic hormones were studied in a patient affected with multihormone-secreting islet-cell tumor.

Fasting glucagon levels (3,000 pg./ml.) rose to 10 ng./ml. following arginine stimulation. While oral glucose load and intravenous glucose infusion did not suppress glucagon secretion, insulin administration induced a prompt depression in glucagon levels. Glucagon, insulin, and gastrin levels were suppressed by somatostatin while calcium infusion caused a paradoxical increase.

It is suggested that only some of the stimulation-inhibition mechanisms were conserved in this case of glucagon-secreting pancreatic tumor.
Significant Muscle Capillary Basement Membrane Thickening in Spontaneously Diabetic Mystromys Albicaudatus
Authors: Yesus Yohannes W , Esterly James A , Stuhlman Robert A , Townsend John F
Published: September 2013

Skeletal muscle capillary basement membrane thickness was determined in age- and sex-matched normal and spontaneously diabetic Mystromys albicaudatus. In nondiabetic animals the average basement membrane thickness was 482.6 ± 48.7 Å as against 779.0 ± 319.9 Å in the diabetic ones. This difference was statistically significant at P<0.005.
Coronary Heart Disease in the Pima Indians: Electrocardiographic Findings and Postmortem Evidence of Myocardial Infarction in a Population with a High Prevalence of Diabetes Mellitus
Authors: Ingelfinger Joseph A , Bennett Peter H , Liebow Irving M , Miller Max
Published: September 2013

The frequency of electrocardiographic evidence of coronary heart disease (CHD) and the rate of autopsy-proved myocardial infarction were determined in the Pima, a tribe of American Indians with a high prevalence of diabetes mellitus. The electrocardiograms of 701 Pimas, aged 40 years and over (85 per cent of the adult reservation population, 45 per cent of whom had diabetes) were read according to the Minnesota Code, and 120 postmortem examinations were reviewed for evidence of myocardial infarction. The frequency of CHD as evidenced by major Q-wave changes in the Pima (1.6/100) was about one-half that found in Tecumseh, Michigan (p<0.10). The relatively low rate of myocardial infarction at autopsy (15 per cent of males and 8 per cent of females aged 40 years and over) was consistent with the low prevalence of Q-wave changes. The subjects with diabetes had a higher rate of CHD than nondiabetics, both electrocardiographically and at postmortem examination, although the differences were not statistically significant. The low prevalence of CHD in the living Pima and the low rate of infarction at autopsy indicate that this tribe has a low frequency of CHD despite the extraordinarily high prevalence of diabetes mellitus.
Evaluation of a ‘True’ Fractional Removal Rate of Glucose in Man by Bolus and Simulated-ramp Increase of Glucose
Authors: Rosenqvist Urban , Ličko Vojtech , Karam John H
Published: September 2013

An infusion method designed to produce a gradual ramplike rise in plasma glucose levels in man showed that the observed slope of the ramp was not significantly different from the calculated slope only when both of the following parameters were used:

1. When the glucose disappearance rate coefficient (k) was calculated by an incremental method in which the fasting plasma glucose level was subtracted from each plasma glucose value obtained during a standard rapid intravenous glucose tolerance test. This proved to be superior to a contrasting method in which absolute glucose values are used for the semilogarithmic plot of glucose concentration versus time.

2. When the dilution technic was used to estimate directly the volume distribution of glucose rather than relying on standard reference tables that predict glucose distribution space in man.

By using these two parameters obtained during standard intravenous glucose tolerance testing, we have shown that it is possible to calculate the rate of glucose infusion required to achieve successfully in man a ramp of plasma glucose of any desired steepness and to characterize the consequent insulin secretion. This simulated ramp increase of glucose provides a potentially useful tool for investigation of the dynamics of islet-cell function in man.
Insulin Response to Oral Glucose in Patients with a Previous Myocardial Infarction and in Patients with Peripheral Vascular Disease: Hyperinsulinism and Its Relationships to Hypertriglyceridemia and Overweight
Authors: Sorge Franco , Schwartzkopff Wolfgang , Neuhaus Günter A
Published: September 2013

The insulin response to an oral glucose load (100 gm.) in 127 patients with a previous myocardial infarction (MI) (six months to one year) and in 65 patients with surgically treated or arteriographically identified peripheral vascular disease (PVD) was compared with that of 89 controls after matching the three collectives for age, glucose tolerance, and per cent ideal body weight (% IBW). The insulin response was of greater magnitude in MI and PVD groups than in respective control groups also in the absence of hyperglycemia, hypertriglyceridemia, and obesity. This finding suggests that hyperinsulinism may represent an early metabolic alteration associated with the development of MI and PVD. The insulin secretion pattern was prevalently of the delayed type in association with impaired glucose tolerance and with hypertriglyceridemia but not with overweight.

Correlations between serum insulin, triglyceride (TG) levels, and % IBW were also investigated. We found a strong correlation (p < 0.001) between stimulated insulin levels and % IBW in MI patients and none in PVD patients; conversely, the correlation between serum insulin and TG levels was very high (p < 0.001) in PVD patients and only weak (p < 0.05) in MI patients. No correlation was found between cholesterol (CH) levels and any of the other parameters studied. According to these results, it seems likely that hyperinsulinism plays a major role as a closely associated factor to obesity in those subjects who develop an MI, whereas in PVD patients the raised insulin levels may favor lipid accumulation in the arterial intima and accelerate the progress of atherosclerosis.
Studies on Streptozotocin Diabetes
Authors: Ganda Om P , Rossini Aldo A , Like Arthur A
Published: September 2013

Both alloxan and streptozotocin produce β-cell necrosis in the rat. Previous studies have shown protection against alloxan toxicity by D-glucose, D-mannose, and the nonmetabolized analogue 3-0-methyl-D-glucose and removal of this protective effect by D-mannoheptulose. The effect of several agents (i.v. infusion) against the β-cell toxic effect of streptozotocin (60 mg./kg. i.v. in 24-hour-fasted 200-gm. male rats) was studied. Protection was determined by plasma glucose concentrations 24 and 48 hours later and, in certain experiments, by histologic examination of the islets.

D-glucose and D-mannose provided no protection. Similarly, D-galactose, D-fructose, α-methyl-D-glucoside, D-L-glyceraldehyde, D-xylose, and D-glucosamine had no effect. However, 3-0-methyl-D-glucose administered immediately before streptozotocin resulted in progressive inhibition of β-cell toxicity with complete protection at 0.83 mMoles per rat. The protective effect of 3-0-methyl-D-glucose was not altered by mannoheptulose. 2-Deoxy-D-glucose, which has no effect against alloxan, provided nearly complete protection against streptozotocin at 2.2 mMoles per rat. The effects of 3-0-methyl-D-glucose and 2-deoxy-D-glucose were additive and were not altered by glucose. Furthermore, the 3-0-methyl-D-glucose as well as 2-deoxy-D-glucose protective effects were still present, albeit attenuated, when these agents were given following the administration of streptozotocin. This is in contrast to alloxan, against which 3-0-methyl-D-glucose provides protection only when given before alloxan.

3-0-Methyl-D-glucose is the only carbohydrate protective against both streptozotocin and alloxan in the rat. However, several silent differences seem to exist between the mechanisms of beta-cytotoxic effects of these two diabetogenic compounds.
Stimulation of Glucagon Secretion by Scorpion Toxin in the Perfused Rat Pancreas
Authors: Johnson David G , Ensinck John W
Published: September 2013

Toxin from the scorpion Leiurus quinquestriatus was used to release norepinephrine from sympathetic nerve endings in the perfused rat pancreas. Addition of toxin, 10μg./ml., to perfusate containing 0.3 mg./ml. glucose caused a large increase in release of norepinephrine and glucagon. Glucagon secretion was suppressed by perfusate containing 3.0 mg./ml. glucose but still responded to stimulation with scorpion toxin. Atropine, 10 μM, had no effect on either norepinephrine or glucagon release in response to scorpion toxin. The release of glucagon was blocked by 100 μM propranolol, 10 μM phentolamine, or 30 μM phenoxybenzamine. Somatostatin, 55 nM, did not affect the release of norepinephrine by scorpion toxin but totally inhibited the glucagon response. These results suggest that pharmacologic stimulation of the adrenergic nerve endings in the rat pancreas can elicit a rapid release of glucagon. This response can be prevented by appropriate concentrations of either alpha or beta adrenergic blocking agents or somatostatin.
Immunopathology of Renal Extracellular Membranes in Kidneys Transplanted into Patients with Diabetes Mellitus
Authors: Mauer S Michael , Miller Kenneth , Goetz Frederick C , Barbosa Jose , Simmons Richard L , Najarian John S , Michael Alfred F
Published: September 2013

Kidneys of patients with severe diabetic nephropathy demonstrate marked linear immunofluorescent staining of extracellular membranes, including the tubular and glomerular basement membranes (TBM and GBM) and Bowman's capsule. Immunofluorescent studies were carried out on kidney tissue obtained from 12 diabetic and 17 nondiabetic patients from two to 12 years following renal transplantation. The frequency and intensity of IgG and albumin staining of these membranes were significantly greater in the diabetic than in the nondiabetic patients (P <0.0005). TBM, GBM, and Bowman's capsule staining did not occur in any of the seven kidneys studied at the time of their transplantation into diabetic recipients.

Thus, the abnormalities leading to the deposition or trapping of proteins in renal extracellular membranes occur early after the placement of normal kidneys into the abnormal metabolic environment of the diabetic transplant recipient. The present study supports the concept that basement membrane alterations in diabetes are a consequence of the biochemical perturbations of diabetes rather than a separately inherited genetically linked disorder.
Total Cardiac Denervation in Diabetic Autonomic Neuropathy
Authors: Lloyd-Mostyn R H , Watkins P J
Published: September 2013

Total loss of the autonomic regulation of heart rate is described in a 28-year-old diabetic with extensive autonomic neuropathy. The patient had an almost fixed heart rate that barely responded to any of the tests that stimulate or inhibit the autonomic nerves. Its behavior was similar to that of the transplanted heart.
Effect of Ethanol on the Glucose-mediated Insulin Release in Triply Catheterized Anesthetized Pigs
Authors: Kühl C , Andersen O , Jensen S Lindkaer , Nielsen O Vagn
Published: September 2013

In order to further elucidate the potentiating effect of ethanol on the glucose-mediated insulin response, triply catheterized anesthetized pigs were submitted to an intravenous glucose infusion test after a four-hour preinfusion with ethanol (11 pigs) or saline (six pigs, control experiment). During the tests portal, hepatic, and peripheral venous blood was drawn simultaneously. Two series of ethanol-preinfusion experiments were carried out: in one series the serum ethanol concentration was maintained at ∼ 10 mM and in the other at 19 mM. Compared with saline, 10 mM of serum ethanol induced a more than threefold increment in the insulin secretory response to glucose as estimated in the portal blood (p < 0.01). Likewise, hepatic and peripheral venous blood insulin levels were enhanced (p < 0.01). In contrast, 19 mM of serum ethanol did not elevate serum insulin levels above those found in the control experiments. When individual incremental portal insulin areas were plotted against the corresponding average value of serum ethanol in the preinfusion period, a significant inverse relationship was found (p < 0.02), indicating a decrease in the potentiating effect of ethanol on the glucose-mediated insulin response with increasing levels of serum ethanol. Comparison of portal and hepatic incremental insulin areas revealed that ethanol did not, in the concentration range investigated, influence the hepatic insulin degradation rate. In conclusion, ethanol seems to potentiate, in an inverse concentration-dependent manner, the glucose-mediated insulin response through an action directly on the pancreas.
Glucagon Release Precedes Insulin Release in Response to Common Secretagogues
Authors: Pek S , Tai T -Y , Crowther R , Fajans S S
Published: September 2013

The dynamics and interrelationships of glucagon and insulin secretion were studied in the isolated perfused rat pancreas by utilizing a series of compounds that stimulate the release of both hormone. Leucine, arginine, prostaglandins F2α and E2, bovine growth hormone, and isoproterenol were administered individually over 60-second intervals. The release of glucagon preceded that of insulin in response to all compounds tested. The rapidity of glucagon release varied in response to different secretagogues; the time course of insulin release was fairly constant. The timing and the magnitude of glucagon and insulin release did not correlate statistically. Conclusions: (1) pancreatic alpha cells respond more rapidly than beta cells to the same stimulus; (2) antecedent release of glucagon is not the principal mediator of insulin release in response to stimuli common to both hormones; and (3) endogenous glucagon may at best modify the release of insulin evoked by certain secretagogues.
A Method for Studying Acute Insulin Secretion and Glucose Tolerance in Unanesthetized and Unrestrained Rats: The Effect of Mild Stress on Carbohydrate Metabolism
Authors: Shah Jayendra H , Wongsurawat Nirandon , Aran Peter P , Motto George S , Bowser E Nelson
Published: September 2013

A technique is described for glucose infusions and for frequent sampling of small quantities of blood in unrestrained and unanesthetized small laboratory animals. Under pentobarbital anesthesia, polyethylene catheters were implanted into the jugular vein and the aorta, and distal ends were exteriorized on the back of the neck of 250-gm. rats. Five to seven days following surgery the rats regained weight and were in a normal anabolic state, despite indwelling catheters. On the day of the intravenous glucose tolerance test (ivGTT), the exterior ends of the indwelling jugular and aortic catheters were connected to specially prepared extension catheters, through which a glucose pulse was given and frequent blood samples in small quantities were collected, respectively. During the entire procedure, the animals were resting quietly, unrestrained and unanesthetized. In another group of similar rats with indwelling catheters, ivGTT was performed after they were restrained in plastic restrainers. During the ivGTT, serum glucose levels were significantly higher in the restrained rats than those observed in the control rats. The mean glucose disposal rate (K) of 2.2 ± 0.2 was significantly slower in restrained rats than the K of 3.0 ± 0.3 in unrestrained rats. Following the glucose pulse, insulin secretion was significantly lower in restrained rats than that observed in the unrestrained rats. These observations emphasize the importance of controlling the modifying effects of mild stress on glucose tolerance and insulin secretion.
Abnormalities of Endogenous Glucagon and Insulin in Unstable Diabetes
Authors: Reynolds Clayton , Molnar George D , Horwitz David L , Rubenstein Arthur H , Taylor William F , Jiang Nai-Siang
Published: September 2013

The responses of glucagon, growth hormone, and insulin secretion to the oral administration of glucose and to the intravenous infusion of saline, arginine, and insulin were measured in seven patients who had stable diabetes, eight who had unstable diabetes, and seven healthy volunteers. Hyperglycemia suppressed secretion of glucagon in normal subjects but not in diabetics. The oral glucose and arginine infusion tests demonstrated partial preservation of insulin-secretory ability in stable diabetics and its virtual absence in unstable diabetics. Glucagon responses to arginine infusion were similar in all three groups. In response to hypoglycemia induced by insulin infusion, the concentrations of plasma glucagon increased in normal subjects and, to a lesser extent, in stable diabetics but increased in only two of the unstable diabetics. The impairment in glucagon response during hypoglycemia in diabetics correlated positively with the degree of diabetic instability and insulin deficiency during glucose and arginine testing. The severity of the insulin deficiency also correlated with the degree of diabetic instability. These findings support the hypothesis that inherent abnormalities of insulin and glucagon secretion may account for many of the clinical characteristics of unstable and stable diabetic patients.
Cigarette Smoking and Diabetic Retinopathy
Authors: Paetkau Margaret E , Boyd T A S , Winship Bruce , Grace Michael
Published: September 2013

A sample of 181 diabetics with diabetic retinopathy was statistically investigated with regard to association of smoking with proliferative retinopathy. The numbers of patients with proliferative retinopathy rose with increasing tobacco consumption. In nonsmokers no association existed between diabetes duration and proliferative retinopathy, but in smokers the number with proliferative retinopathy rose with increasing diabetes duration.
Glucose and 3-0-Methylglucose Protection Against Alloxan Poisoning of Pancreatic Alpha and Beta Cells
Authors: Pagliara Anthony S , Stillings Susan N , Zawalich Walter S , Williams Ann D , Matschinsky Franz M
Published: September 2013

Alloxan infused into the isolated perfused rat pancreas caused transient insulin secretion and permanent suppression of amino-acid-stimulated glucagon release. Alloxan poisoning also prevented subsequent induction of glucose-mediated insulin release and also prevented the inhibition of glucagon release by glucose. Glucose or 3-0-methylglucose infused simultaneously with alloxan protected the α-and β-cell, allowing subsequent glucose inhibition of glucagon secretion and stimulation of insulin release. The above alloxan effects were dose-related, the α-cell being one fourth as sensitive to alloxan as the β-cell.

The data indicate-that (1) alloxan and glucose suppression of amino-acid-stimulated glucagon secretion is independent of concomitant insulin secretion; (2) alloxan, like glucose, affects α-and β-cells directly, stimulating the β-cell and inhibiting the α-cell; and (3) alloxan acts on a glucoreceptor system with comparable physicochemlcal characteristics common to both cell types.
Insulin Antibodies and Clinical Complications in Diabetics Treated for Five Years with Lente or Sulfated Insulin
Authors: Little J A , Lee R , Sebriakova M , Csima A
Published: September 2013

The antigenlcity of two types of insulin and their effect on diabetic control and complications were studied for 66 months in two groups of diabetics not treated previously with insulin. The groups were similar in age, weight, duration of the disease, and other biochemical and clinical findings. None of the patients developed brittle diabetes or became insulin-resistant, and both groups were controlled initially on an average of 30 U. of insulin daily. Plasma insulin antibodies and their avidities were measured by a modification of the insulin radioimmunoassay. Sulfated insulin was found to be less antigenic than lente throughout the treatment (p < 0.001). In the sulfated group the antibody index averaged 22 μU/ml. over the five years and did not change significantly with time. In the lente group there was a peak at six months of 2,161 μU./ml. and then a gradual and significant decrease to 88 μU./rnl. at 66 months.

The avidity of the antibodies in the sulfated group was initially higher than in the lente group (2.491 vs. 1.972, p < 0.001). In the sulfated group it did not change with time, whereas in the lente group the avidity increased with time and became similar to that in the sulfated group. In both groups there was a significant negative correlation between antibody index and avidity throughout the study, ranging from −0.510 to −0.927 (p < 0.05 to < 0.001). In the sulfated group the insulin dose decreased with time (b = −2.56, p < 0.001), whereas in the lente group it tended to increase. The incidence of local skin reactions at the injection sites was lower throughout the study in the sulfated group (p < 0.01). Low levels of insulin autoantibodies (0.03 to 4 μU./ml.) were found in 4 per cent of untreated diabetics and in 6 per cent of normal subjects (0.46 to 0.52 μU./ml.).
The Regulation of Plasma Ketone Body Concentration by Counterregulatory Hormones in Man I. Effects of Norepinephrine in Diabetic Man
Authors: Schade David S , Eaton R Philip
Published: September 2013

Previous studies have attributed norepinephrine's ketogenic activity to its ability to mobilize peripheral fat stores. This study was designed to determine whether norepinephrine has ketogenic activity independent of its lipolytic effect in diabetic man.

Six insulin-dependent diabetic subjects were infused with pathophysiologic concentrations of norepinephrine (0.08 μg./kg./ min.). As a control for norepinephrine's lipolytic effect, a separate heparin-induced free fatty acid generation study was performed on each subject. The results demonstrate, for the first time in man, that norepinephrine has ketogenic activity independent of its lipolytic effect. Furthermore; physiologic elevations of norepinephrine concentration were also demonstrated to increase plasma glucagon concentration. Our data are consistent with the possibility that the rise in concentration of glucagon may have a participated in the catecholamine-augmented ketogenesis.
Plasma Androgen Concentrations in Diabetic Women
Authors: Szpunar Walter E , Blair A James , McCann Daisy S
Published: September 2013

Plasma androgen levels were determined in women assigned to the following groups: idlopathically hirsute, diabetic, both idiopathkally hirsute and diabetic, and normal. The androgens examined were androstenedione (AD), dihydrotestosterone (DHT), testosterone (T), and dehydroepiandrosterone (DHEA). We And statistical differences between young (<38 years) and older (≥38 years) controls at confidence levels of p≤ 0.01 for AD, DHT, and T and of p≤ 0.05 for DHEA. The results indicate that peak circulating androgen levels occur prior to age 30-35 years for women. There are no significant differences between the young controls and young idiopathkally hirsute subjects, but a statistical difference exists between older hirsute and older controls for all four androgens (p≤ 0.05).

When a comparison is made among the diabetic, hirsute dia-betk, and older control groups (all groups ≥38 years), the diabetic group is significantly higher than the control in plasma AD (p≤ 0.01) and DHEA (p≤ 0.05). These same two steroids are also higher in the diabetk group than in the hirsute diabetic group (p≤ 0.05), while the latter differs from controls only in testosterone levels (p≤ 0.05). DHT levels are similar for all three groups.
Rapid Conversion by Insulin of Hepatic Intermediary Metabolism from Glucose Production to Glucose Utilization in the Liver of Alloxan-diabetic Rats
Authors: Seitz H J , Müller M J , Krone W , Tarnowski W
Published: September 2013

The concentration of free fatty adds in the blood, the tissue concentrations of hepatic cyclic AMP, long-chain acyl-CoA (LCA), adenine nucleo tides, inorganic phosphate, the intermediates of the Embden-Meyerhof pathway and the citric acid cycle (including acetyl-CoA and free CoA), and the cytoplasmic and mitochondrial redox couples were determined in alloxan-diabetic rats 15, 30, 60, and 90 minutes after insulin injection. From the meared values, the energy state of the adenine nucleotide system in the liver, the redox state of the NAD system, and the concentrations of malate, oxaloacetate, citrate, and α-ketoglutarate were estimated for the cytoplasmic and mitochondrial compartment by the use of established calculation methods.

Insulin injection into alloxan-diabetic rats caused a rapid decline in the concentration of serum free fatty acids and a coordinate decline in hepatic LCA concentration. The latter alteration was accompanied by an increase in the cytoplasmic and a synchronous decrease in the mitochondrial ATP/ADP×P ratio. Simultaneously, the redox state of the cytoplasmic NAD system was shifted towards the oxidized state. When the appropriate data were plotted against each other, a highly significant correlation between the concentration of free fatty acids in the blood and that of LCA in the liver, between the hepatic LCA concentration and the cytoplasmic energy state, and between the cytoplasmic energy state and the cytoplasmic redox state was obtained. These findings are interpreted to support the hypothesis derived from in-vitro experiments that insulin, because of the concentration of hepatic LCA, might affect the translocation of adenine nucleotides between the cytoplasmic and the mitochondrial compartment, thereby regulating the cytoplasmic energy state and, consequently, the redox state of the cytoplasmic NAD system.

Insulin injection into alloxan-diabetic rats provoked rapid, coordinate changes in the concentration of the intermediates of both the citric acid cycle and the Embden-Meyerhof chain, indicating the altered substrate flow through these pathways. Thosemetabolit s known to modulate the activity of key regulatory enzymes in vitro were analyzed with respect to their proposed regulatory function. As to the insulin-induced shift from pyruvate carboxylatlon to pyruvate decarboxylatIon, the data reveal that the decrease in pyruvate carboxylase activity can be attributed to the decrease in the intramitochondrial ATP/ADP ratio and the simultaneous fall in acetyl-CoA concentration, while the coordinate increase in pyruvate dehydrogenase activity can be ascribed to the decline in the concentration of LCA and, consequently, in the ratios of ATP/ADP, NADH/NAD, and acetyl-CoA/CoA within the mitochondria.
Cholinergic Blockade in Reactive Hypoglycemia
Authors: Permutt M Alan , Keller David , Santiago Julio
Published: September 2013

The effects of cholinergic blockade on the plasma glucose and insulin responses during oral and intravenous glucose administration were studied. Propantheline (30 mg.) was given by mouth 45 minutes before standard glucose tolerance testing to produce symptomatic cholinergic blockade. In 10 normal subjects a flattening of the over-all plasma glucose response to oral glucose was observed compared with the control test, whereas insulin secretion was not different. In seven patients with repeated episodes of symptomatic reactive hypoglycemia, cholinergic blockade eliminated both symptomatic and chemical hypoglycemia in each, raising the mean nadir glucose from 44 ± 4 mg./dl. to 84 ± 8 mg./dl. (p<0.01) and significantly reducing insulin secretion. In contrast, following intravenous glucose challenge, cholinergic blockade produced no significant difference in the rate of glucose utilization or insulin secretion in either group.

These results are compatible with the hypothesis that excessive vagal stimulation may contribute to the hypoglycemia seen in patients with reactive hypoglycemia but suggest that the predominant effect is on the gastrointestinal tract rather than on pancreatic islets directly. These studies confirm that anticholinergic drugs may be useful adjuvants in treating these patients.
Blood Glucose, Insulin, and Free Fatty Acid Levels During Oral Glucose Tolerance Tests in 158 Obese Children
Authors: Deschamps I , Giron B J , Lestradet H
Published: September 2013

In 158 obese children, aged from three months to 15 years, blood glucose, immunoreactive insulin, and free fatty acid levels were measured during a standard oral glucose tolerance test carried out prior to treatment. The results were analyzed for the total sample as well as for three age groups: 0–5 years, 6–10 years, and 11–15 years and compared with those of 70 normal-weight children matched for age and sex.

Glucose tolerance is normal in the obese children. It is different from the controls only two hours after glucose loading, when a slight but significant elevation is found. The glucose levels at one and two hours are significantly higher in the obese children of group III than in the younger ones.

Fasting F.F.A. levels are similar in normal and obese children, but the F.F.A. decrease following glucose absorption is significantly diminished in the obese. The F.F.A. levels of the youngest obese are significantly higher than those of the older ones.

A constant and important hyperinsulinism, fasting and postabsorptive, is demonstrated in obese children of all ages, even before five years and at the beginning of obesity. Age- and sex-related differences in insulin secretion are much more marked in the obese than in normal children. The degree of hyperinsulinemia is related to the degree of obesity, but not to its duration.

The results suggest that hyperinsulinism is associated with obesity from its onset rather than being a long-term consequence of overweight. However, the origin of hyperinsulinism in obesity and the mechanism of insulin resistance still remain obscure.
Relation of Fasting Plasma Glucose Concentration to Plasma Insulin and Glucagon Concentrations: Studies in Latent Diabetics and Women Who Have Produced Large-for-dates Babies
Authors: Turner R C , Harris E , Bloom S R , Uren C
Published: September 2013

Mothers who have had gestational diabetes (latent diabetics—LD), as well as those who have produced a large-for-dates baby (LFD) but who were not known to have been diabetic, have raised fasting plasma glucose levels, and these may induce fetal overnutrition. The increased birth weight of babies of obese mothers may also be due to their raised fasting plasma glucose levels.

LD and LFD have normal or raised fasting plasma insulin levels even though they have both decreased insulin secretion to small changes in plasma glucose and normal or increased insulin sensitivity. The high fasting plasma glucose probably results from the decreased insulin-secretory response to glucose. Normal subjects have little day-to-day variation of their fasting plasma glucose, whereas subjects with a high fasting plasma glucose have less precise control.

Although LD and LFD had abnormal insulin responses, they have normal plasma glucagon concentrations that do not correlate with glucose tolerance or insulin sensitivity. The reported abnormalities of glucagon in diabetes are probably a secondary, not a primary, event.
Habitual Physical Activity and Glucose Tolerance: Males Age 16–64 in a Total Community
Authors: Montoye Henry J , Block Walter D , Metzner Helen , Keller Jacob B
Published: September 2013

The data being reported are part of an epidemiologic study of health and disease in an entire community, Tecumseh, Michigan. Approximately 1,300 males age 16–65 were classified into three groups on the basis of their habitual leisure and occupational physical activity. A blood sample was drawn one hour after a glucose challenge and analyzed for glucose concentration. A measure of body fatness (sum of four skinfolds) was also available on the men. Glucose concentration of the three physical activity groups was compared by analyses of variance within narrow age groups. There was no significant relationship between glucose tolerance and habitual physical activity. There was a slight, but in some age groups significant, relationship between glucose tolerance and body fatness. The population was then divided within each age group into subgroups (thirds) by sum of skinfolds. The analysis was repeated in each age-fatness group. Glucose tolerance was better in the active men but only among the leanest subgroup of subjects.
Potentiation of Hypoglycemic Effect of Chlorpropamide and Phenformin by Halofenate
Authors: Kudzma David J , Friedberg Samuel J
Published: September 2013

The potentiation of oral hypoglycemic drugs by the antilipemic agent halofenate is reported. Forty-seven diabetic patients were treated for 48 weeks with halofenate, clofibrate, or placebo. Five patients in the halofenate group were taking phenformin plus either chlorpropamide or tolbutamide. Their average initial fasting plasma glucose was 160 mg./dl. All five patients experienced a slow but substantial fall in fasting plasma glucose. The mean fasting plasma glucose for the five patients after 80 days of halofenate treatment was 63 mg./dl. As oral treatment for diabetes was reduced, the fasting plasma glucose returned to prehalofenate levels. In this study, we did not detect an effect of halofenate on the fasting plasma glucose of diabetic patients treated with insulin or on the fasting plasma glucose levels of patients treated with diet alone.
The Effect of Chronic Oral Antidiabetic Therapy on Insulin and Glucagon Responses to a Meal
Authors: Tsalikian Eva , Dunphy Thomas W , Bohannon Nancy V , Lorenzi Mara , Gerich John E , Forsham Peter H , Kane John P , Karam John H
Published: September 2013

Nineteen maturity-onset diabetic patients receiving oral hypoglycemic therapy in a university diabetes dinic completed a study to assess the efficacy of the oral agents and to determine their effects on pancreatic islet hormone secretion. All patients were receiving sulfonylureas, and seven were also receiving phenformin. Hie subjects were studied as outpatients in the clinic setting on four different occasions with collections of a baseline blood sample before a standard breakfast and a second sampling two hours postprandially, twice while on their prescribed medication and twice after having been withdrawn from the medication. The values obtained during the two studies on and the two studies off medications were reproducible for each subject. Analysis of the results by paired differences revealed that mean 24-hour urine glucose values deteriorated significantly (p < 0.005) after oral antidiabetic therapy was withdrawn; similarly, mean plasma glucose values, both at baseline and two hours postprandially, rose significantly (p < 0.001) when subjects were off medication. Baseline serum insulin values were not changed, but postprandial levels were significantly higher on oral agents (p <0.005). Plasma immunoreactive glucagon was significantly lower both at baseline (p < 0.02) and postprandially (p < 0.005) when the subjects were on their antidiabetic medications. During the trial off medication, 16 patients became symptomatic, with three of these developing symptoms severe enough to require hospitalization.

It is apparent from this study that oral hypoglycemic medications can play a role in controlling symptoms in maturity-onset diabetic patients and that the beneficial effect of these agents on hyperglycemia may, in part, be explained by their stimulation of endogenous insulin secretion and partial suppression of endogenous glucagon.