bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin Secretion in Relation to Adipose Tissue in Men
Authors: Björntorp Per , Berchtold Peter , Tibblin Gösta 
Published: December 2014

In a group of eighty-one fifty-five-year-old men, randomly selected from the total population, and in a group of twelve medical students, twenty-three years of age, body composition and adipose tissue fat cell size and number were determined. A 100 gm. peroral glucose tolerance test was performed, and blood glucose and plasma immunoreactive insulin were examined.
The older men showed higher glucose and particularly higher insulin responses after the glucose tolerance test than the young men. In lean older men, selected after ponderal index or body fat measurements, this was less pronounced. When a group of older men with the same fat cell diameter as the younger men was selected, the differences in glucose-insulin responses were still smaller and almost nonexisting between the two age groups. Fat cell diameter correlated only partially with ponderal index and body fat.
It was concluded that adipose tissue fat cell size is a more important determinant than adipose tissue size for the glucose and insulin res glucose tolerance test. Age has a relatively minor influence.
Clinical and Metabolic Characteristics of Hyperosmolar Nonketotic Coma
Authors: Gerich John E , Martin Malcolm M , Recant Lillian 
Published: December 2014

Clinical and metabolic data of twenty patients with hyperosmolar nonketotic coma (HNC) and ten patients in keto-acidosis (DA) are compared. HNC patients were older; fewer were previously known diabetics; more had multiple chronic diseases. Common precipitating factors in HNC included infection, dehydration and administration of diabeto-genic drugs. Blood glucose and urea nitrogen, plasma sodium, bicarbonate and osmolarity were significantly higher in HNC. Plasma potassium and chloride levels were similar in both groups. Patients with HNC had significantly lower plasma levels of free fatty acids, cortisol and growth hormone.
Plasma insulin levels in HNC were low and not significantly different from those observed in KA. Patients with HNC required more fluids and less insulin therapy. Mortality was 20 per cent in HNC, lower than that generally observed in this condition, but higher than that of KA, 0 per cent.
On the basis of the above findings, it is suggested that dehydration and hyperosmolarity may play significant roles in the etiology of HNC, and that therapy should, therefore, be directed at restoration of normal osmolarity and correction of water deficits with 0.45 per cent saline and moderate amounts of insulin.
Degradation of Insulin and Proinsulin by Various Organ Homogenates of Rat
Authors: Kitabchi Abbas E , Stentz Frankie B , Bobal Mary A 
Published: December 2014

Degradation of biologically active and immunoreactive insulin and proinsulin was studied in the particulate and soluble fractions of homogenates of liver, brain, fat, lung, kidney, spleen, heart, muscle, pancreas, and testis of four groups of male rats at various time intervals. In addition, the above studies were also conducted in the ovaries, muscles, and adrenals of one group of female rats. Approximately 90 per cent of the degradative activity for immunoreactive insulin and immunoreactive proinsulin was located in the supernatant fraction with the remaining in the particulate fraction. The rate of degradation of immunoreactive insulin in the supernatant fraction expressed as picomoles destroyed per minute per gram of tissue was 53.8, 27.2, 26.6, 26.6, 25.0, 24.3, 14.1, 13.0, 11.5, 8.0, 5.9, and 1.7 for liver, pancreas, kidney, testis, adrenal, spleen, ovary, lung, heart, muscle, brain, and fat, respectively.
With the exception of pancreas and kidney, no organ extract exhibited greater than 10 per cent of immunoreactive proinsulin degradation as compared to immunoreactive insulin. The rate of immunoreactive proinsulin degradation (picomoles per minute per gram of tissue) in the supernatant fraction was 5.0, 5.0, 5.0, 2.4, 2.0, 2.0, 1.6, 1.6, 1.0, 1.0, 0.6, and 0.2 for liver, pancreas, kidney, adrenal, testis, spleen, ovary, lung, heart, muscle, brain, and fat, respectively.
Studies on partially purified insulin protease of kidney indicated (a) an approximately tenfold greater rate for degradation of insulin than proinsulin and no appreciable degradation of intermediate II; (b) degradation of intermediate I was approximately one-third as much as that of insulin; (c) addition of other hormones such as ACTH, glucagon, and growth hormone did not affect the degradation rate of insulin; (d) an inhibition of the enzyme by the sulfhydryl group inhibitor and by heating at 60° for five minutes; (e) a lack of effect of glutathione or trasylol; (f) a pH optimum of 7.4 to 7.6; and (g) a Km for insulin of 2 × 10−8 M. These properties all agree with similar findings of enzyme systems in liver and muscle, and suggest a similar degree of selectivity for degradation of insulin.
Serum N-acetyl-beta-glucosaminidase Activity in Diabetic Patients
Authors: Belfiore Francesco , Napoli Elena , Vecchio Luigi Lo 
Published: December 2014

In a group of seventy-three diabetics, a statistically significant (P &lt; 0.001) increase (+ 41 per cent) of serum N-acetyl-beta-glucosaminidase activity was found. The enzyme level seemed to correlate with both the vascular complications (either microangiopathic or macroangiopathic in nature) and the blood sugar level measured simultaneously. In fact, in patients with moderately elevated glycemia (145 mg./100 ml. ± 41) and without vasculopathies, the enzymatic activity was slightly changed (P &gt; 0.05), while the activity was significantly (P &lt; 0.001) increased (+ 31 per cent), in diabetics with essentially similar gly-cemia (151 mg./100 ml. ± 30) but with vasculopathies, and even more elevated (+ 80 per cent, P &lt; 0.001) in diabetics without vasculopathies but with marked hyper-glycemia (309 mg./100 ml. ± 160).
Since lysosomal enzymes, to which N-acetyl-beta-glucosaminidase belongs, are capable of degrading various compounds, these enzymatic changes were regarded as due to an activation of lysosomal enzymes in tissues, occurring in diabetes in response to the metabolic need of degrading either mucopolysaccharides and glycoproteins (as in diabetics with vasculopathies), or various constituents of cells themselves in a context of increased tissue catabolism (as in decompensated diabetics). However, the possibility cannot be excluded that the enzyme is elevated merely because of decreased lysosome stability. Reduction in the destruction rate of the enzyme might also contribute to its elevation.
Blood Glucose Levels During Walking in Normal and Diabetic Subjects
Authors: Klachko D M , Lie T H , Cunningham E J , Chase G R , Burns T W 
Published: December 2014

Blood glucose levels were monitored continuously for twenty-four to thirty hours in twenty-eight normal subjects and fifteen insulin-dependent diabetic subjects. During this period, subjects took standardized exercise consisting of half-mile walks at 4 m.p.h., one at 2½° and two at 5° treadmill slope. The control group showed a modest decrease in glucose concentration (mean, 5.3 mg./100 ml.) during exercise at 2½° slope; during exercise at 5° slope, the decrement in glucose doubled (mean, 11.7 mg./100 ml.). The mean decrement in blood glucose among diabetic patients was greater than that of the control group at both levels of exercise: 24.5 mg./100 ml. at 2½° and 30.0 mg./100 ml. at 5°. These differences were statistically significant. In both groups there was a significant correlation between the magnitude of the decrement in blood glucose and the concentration of glucose at the onset of exercise.
Among control subjects, the blood glucose levels returned to, or exceeded slightly, resting levels within sixty minutes following the exercise period. Among diabetic subjects, the blood glucose tracings resumed the pre-exercise slopes but at a lower level.
These findings demonstrate the significant effect of a brisk half-mile walk on blood glucose levels in insulin-dependent diabetics, and support the clinical observations of the importance of exercise in diabetes control.
New Forms of Insulin
Authors: Galloway John A , Root Mary A 
Published: December 2014

This paper reviews some recent developments in insulin purification and formulation. Neutral Regular insulin (unbuffered Regular insulin with pH adjusted to neutrality, designated NRI) maintained nearly full potency when stored at room temperature for twelve months, while the potency of acid Regular (“commercial”) insulin (ARI) had dropped 20 per cent. When NRI and ARI were administered in combination with NPH or Ultralente insulin, comparable time activity responses were elicited. In fasted normal subjects subcutaneous doses of NRI and ARI gave similar blood glucose responses.
Thirty-seven patients with allergy to commercially available insulin were treated with one or both of two highly purified insulins (single peak and single component pork insulin). Improvement occurred in 78 per cent. Single component insulin was usually, but not always, superior to single peak insulin when both were tested in the same patient.
Insulin was administered orally with an absorption promoter, Brij 98, to twenty normal and thirteen diabetic fasted subjects in crossover studies. Under optimum conditions, definite responses were observed in about 50 per cent of subjects. Serum insulin measurements in the normals and diabetics revealed that increased concentrations were not necessarily associated with falls in blood glucose concentrations in spite of delivery of the insulin by the portal route. Because of the amounts of insulin required, the limitations of test conditions, and a high incidence of nausea, this project has been discontinued.
The Circulating Proinsulin-like Components
Authors: Gorden Phillip , Roth Jesse , Freychet Pierre , Kahn Ronald 
Published: December 2014

Total plasma insulin as measured by radioimmunoassay can be divided into at least two distinct components by gel fitration. One component is indistinguishable from crystalline pancreatic insulin (insulin component); the second component more closely resembles proinsulin (proinsulin-like component).
The proinsulin-like component may be heterogenous in different disease states. Differences in gel filtration properties have been demonstrated between islet cell tumor patients and nontumor patients.
The percentage proinsulin-like component is highest in the basal state; acute stimulation of insulin release predominantly increases the concentration of the insulin component with a resultant decrease in the percentage proinsulin-like component. The same dynamics are seen both in islet cell tumor patients who have high percentages of proinsulin-like component and in nontumor patients. In severely hypoin-sulinemic patients, the percentage proinsulin-like component increases regardless of the etiology of the hypoinsulinemia.
Insulin Content of Fetal Rat Pancreases Grown in Organ Culture and Subsequently Transplanted into Maternal Hosts
Authors: Hegre Orion D , Wells Lemen J , Lazarow Arnold 
Published: December 2014

Portions of pancreases from 19.5-day fetal rats were grown in organ culture on two types of liquid media: low glucose, containing 162 to 170 mg. glucose/100 ml.; high glucose, containing 1,031 to 1,073 mg. glucose/100 ml. Following four days of organ culture, the tissues were extracted and assayed for insulin content (immunoassay). Other cultures were transplanted to maternal hosts at two sites: beneath the capsule of the kidney and into the anterior chamber of the eye. Ten days later, the transplants were removed and assayed for insulin content.
Large quantities of immunologically active insulin were present in the culture media following forty-eight and ninety-six hours of incubation. Expiants exhibited a four- to sixfold increase in insulin content following four days in vitro. Pancreatic expiants cultured on the high glucose medium contained less extractable insulin than similar ex-plants cultured on the low glucose medium.
When cultured expiants were transplanted to hosts with normal blood glucose levels, the total extractable insulin content of the grafts was 55 per cent to 130 per cent greater than that at the time of transplantation. When cultures were transplanted to alloxan diabetic hosts, the total extractable insulin content of the grafts was less than that found in grafts to normal hosts.
A small but statistically significant drop in blood glucose level was observed in hyperglycemie diabetic maternal hosts receiving transplants of organ cultured pancreas.
These results indicate the continued growth and functional responsiveness of the islet beta cells during organ culture and following subsequent transplantation.
Opposite Effects of Aminophylline on Arginine-induced Glucagon and Insulin Secretion in Humans
Authors: Marco Josá , Diaz-Fierros Maruxa , Baroja Isabel M , Villanueva Maria L , Valverde Isabel 
Published: December 2014

The adenyl cyclase-cyclic AMP system, aside from being a mediator of the actions of several hormones, is believed to play an important role in the secretory mechanism of some of these hormones. In young, healthy, nonobese volunteers, we have studied the effect of a large dose (1 gm.) of a cAMP phosphodiesterase inhibitor (aminophylline) on basal plasma glucagon and insulin levels and on the responses of these two hormones to two different doses of arginine.
With a high (468 mg./kg.) and a low (156 mg./kg.) dose of arginine, similar maximal peaks of glucagon concentration were reached, indicating that the level of aminoacidemia reached with the low dose was sufficient to elicit an almost maximal acute response. Plasma insulin and glucose increased as expected after the arginine doses.
With aminophylline alone, plasma insulin and glucose increased slightly but consistently while the level of circulating glucagon did not change (range of the means, 111 pg./ml. ± 28 to 133 pg./ml. ± 25). Aminophylline pretreatment significantly lowered the glucagon response in the late part of the curve corresponding to the high dose of arginine. This inhibitory effect of the xanthine derivative could be due to: (1) peripheral effects of aminophylline, such as increased mobilization of FFA; (2) enhanced removal of glucagon from plasma; (3) direct suppressor effect of cAMP on the alpha cell secretory mechanism. At any rate, this effect of aminophylline seems to be either a retarded one or only present in the late phase of glucagon secretion.
Abnormal Alpha Cell Function in Diabetics Response to Insulin
Authors: Unger R H , Madison L L , Müller W A 
Published: December 2014

The extremely high levels of glucagon recently observed in dogs with severe alloxan-induced diabetes decline promptly and precipitously to normal as soon as exogenous insulin is infused. This suggests that the normal response of the pancreatic alpha cell to hyperglycemia requires the presence of circulating insulin. To determine if the relative hyperglucagonemia of human diabetics responds similarly to insulin repletion, the plasma glucagon response of ten adult-type diabetic patients to a large, predominantly carbohydrate meal was determined with and without the simultaneous forty-five-minute intravenous infusion of glucagonfree insulin (0.12 to 0.2 U./kg.). The glucagon response to the carbohydrate meal during prompt and supernormal hyperinsulinemia resulting from the infusion did not differ from that of the control meal, i.e. normal suppression of glucagon by hyperglycemia was not restored by the abundance of circulating insulin.
To determine if still higher plasma levels of insulin would overcome the hyposuppressibility of the diabetic alpha cell to hyperglycemia, 0.6 U. per kilogram per hour of insulin was infused at a constant rate for two hours together with 0.6 gm. per kilogram per hour of glucose to prevent hypoglycemia. Insulin levels of more than 1,200 μ,U. per milliliter were thus attained. Under these conditions, plasma glucagon declined from a mean preinfusion level of 97 pg./ml. (SEM ± 11) to a nadir of 75 pg./ml. (SEM ± 10) ninety minutes later. This slow, modest, statistically significant (p &lt; 0.01) decline differed strikingly from the response of eight nondiabetic patients given intravenous glucose alone; in these subjects, at a comparable level of hyperglycemia, glucagon declined from a mean fasting level of 90 pg./ml. (SEM ± 8) to 57 pg./ml. (SEM ± 8) within thirty minutes, despite an insulin rise to only 46 μU./ml.
It was concluded that in human diabetics the acute restoration of plasma insulin, even to supernormal levels, does not promptly restore to normal the alpha cell responsiveness to hyperglycemia. Simple insulin lack may not, therefore, adequately explain the alpha cell abnormality in human diabetes.
Muscle Capillary Basement Membrane Changes Related to Aging and to Diabetes Mellitus
Authors: Kilo Charles , Vogler Nancy , Williamson Joseph R 
Published: December 2014

Quantitative electron microscopic studies of muscle capillary basement membrane are reported on 154 control subjects and 151 diabetics. In normal subjects and in diabetics significant thickening of basement membrane is observed as an aging phenomenon in both sexes. Significant age-related sex differences in basement membrane width are evident in normal subjects but not in diabetics. Observations on diabetics suggest that basement membrane width is probably normal in most subjects prior to the onset of carbohydrate intolerance and demonstrate that both the magnitude and incidence of basement membrane thickening increase with longer known duration of carbohydrate intolerance. Basement membrane thickening is demonstrable in a significantly higher percentage of subjects over age fifty (63 per cent) than in subjects under age fifty (25 per cent) who have had the disease for four years' known duration or less. The incidence increases to 90 per cent in subjects with complications of retinopathy and/or nephropathy and to 93 per cent in subjects who have had known disease for twenty years or longer.
Both morphologic and statistical evidence indicate that thickening of basement membranes related to aging and to diabetes is essentially segmental in character.
Role of Lipolytic and Glucocorticoid Hormones in the Development of Diabetic Ketosis
Authors: Chernick Sidney S , Clark Charles M , Gardiner Robert J , Scow Robert O 
Published: December 2014

Pancreatectomized rats hypophysectomized for one week or longer developed ketosis when given dexamethasone and growth hormone in amounts that were relatively inactive when administered alone. Growth hormone could be replaced by other lipolytic hormones, such as adrenocortico-trophic hormone (ACTH) and thyroxine.
When fasted hypophysectomized rats were made acutely diabetic by injection of mannoheptulose, the plasma concentrations of glucose, ketone bodies, free fatty acids (FFA) and glycerol were increased; injection of growth hormone and dexamethasone further increased the concentrations of these plasma constituents. Injection of these hormones increased lipolysis and decreased glucose metabolism, in vitro, by adipose tissue of mannoheptulose-treated hypophysectomized rats. Uptake of FFA and ketogenesis by perfused livers of fasted hypophysectomized rats were directly related to the concentration of FFA in the perfusing fluid. Growth hormone and glucocorticoid did not have an effect on FFA uptake and ketogenesis in the liver.
It is concluded that lipolytic and glucocorticoid hormones induce diabetic ketosis through their actions on adipose tissue. Lipolytic hormones stimulate lipolysis in adipose tissue while glucocorticoid limits, in the absence of insulin, re-esterification of FFA by suppressing the metabolism of glucose. The resultant increased release of FFA to the blood augments, in turn, the concentration of FFA in plasma, the uptake of FFA by the liver, and the formation of ketone bodies in the liver.
Vascular Disease in the Chronic HGH-deficient State
Authors: Merimee Thomas J , Fineberg S Edwin , Hollander William 
Published: December 2014

Twenty-four of thirty-one subjects with human growth hormone (HCH) deficiency but otherwise normal pituitary function were studied over a five year period. Metabolic abnormalities in this group included carbohydrate intolerance, with both increased and decreased insulin secretion, hypertriglyceridemia and hypercholesterolemia. Approximately 50 per cent of the total group manifested a type Ha or lib lipoprotein abnormality.
We established previously that despite these metabolic similarities to subjects with diabetes mellitus, the HGHdeficient subjects did not develop diabetic retinopathy or increased thickness of muscle capillary basement membranes. During the past five years, we have gathered objective data regarding involvement of larger arterial vessels in these patients and in age- and sex-matched diabetics and controls. Whereas 12.5 per cent of the dwarfs and 18.5 per cent of the controls consistently exhibited hypertension (&gt; 150/90), 36 per cent of the diabetics were consistently hypertensive. Only one of twenty-four dwarfs followed for five years evidenced coronary artery or peripheral vascular disease, as indicated by studies including electrocardiograms in basal and stress states; 40 per cent of the diabetics and 5.2 per cent of the controls had findings indicating such disease.
The data would be consistent with an hypothesis that a chronic deficiency of HGH deters the development of both microangiopathic and macroangiopathic pathologic changes to a clinically detectable state. The protective effect may result from an inability of protein synthesis to proceed at normal rates when HCH is absent.
A Simple Method for the Determination of Serum Free Insulin Levels in Insulin-treated Patients
Authors: Nakagawa Shoichi , Nakayama Hidetaka , Sasaki Takashi , Yoshino Koichi , Yu Yune Ying , Shinozaki Kenjiro , Aoki Shin , Mashimo Keimei 
Published: December 2014

A method for the determination of free, active insulin in the sera of insulin-treated diabetics is described. This involved radioimmunoassay after extraction of free insulin with polyethylene glycol. Recovery tests with cold insulin showed 73 per cent recovery of free insulin and no recovery of bound insulin.
The fasting free insulin levels were slightly lower in the patients than in normal persons; exceptions were some patients with complications expected to cause insulin resistance at the peripheral tissue level. Free insulin levels did not correlate with total insulin levels, antibody titers, insulin requirements or conditions of insulin treatment.
A very slight increase of insulin was observed after glucose loading in insulin-treated patients, but a marked increase of the free insulin level followed by an exaggerated increase in the total insulin level was observed in a patient with the insulin autoimmune syndrome.
The diurnal changes of the free insulin suggested the dynamic states of this fraction and its usefulness for determining control of diabetes with insulin.