bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucose Uptake and Production During the Oral Glucose Tolerance Test
Authors: Steele Robert , Bjerknes Clara , Rathgeb Isbel , Altszuler Norman
Published: December 2014

During the three hours required for absorption of most of a U-C-14-glucose load (1 gm./kg.) given orally to an intact unanesthetized dog in the postabsorptive state, about three quarters of the load reaches the peripheral circulation. The absence of randomization of the label, seen when an equal oral load of 6-C-14-glucose is given, indicates that the glucose reaching the peripheral circulation has not been fragmented, then resynthesized into glucose. During the three-hour period, only 0.34 gm. per kilogram of new (unlabeled) glucose is released by liver instead of the 0.63 gm. per kilogram which would have been produced in the absence of oral glucose; the uptake of the glucose of peripheral circulating blood is 1.03 gm. per kilogram instead of 0.63 gm. per kilogram. Endogenous insulin secreted in response to the oral load exerts a somewhat larger effect to decrease hepatic glucose release (relative to the increase in glucose uptake from peripheral blood) than is the case when insulin is given by peripheral vein.
Glucose Intolerance in Hypernatremic Rats
Authors: Nitzan Menachem , Zelmanovsky Sophia
Published: December 2014

A study has been made of the effect of hypernatremia on carbohydrate metabolism in the rat. It was shown that rats rendered hypernatremic by subcutaneous injections of hypertonie sodium solutions manifest increased fasting blood glucose levels, as well as a decreased ability to dispose of an exogenous glucose load.

The mechanism by which hypernatremia alters carbohydrate metabolism has not been determined. However, an impairment of normal cellular functions known to accompany hypertonicity of body fluids as well as disturbed secretion of the hormones which regulate carbohydrate metabolism, could explain the metabolic abnormality.
A Study in the Pathogenesis of Hyperlipemia in a Patient with Acromegaly and Diabetes Mellitus
Authors: Camitta Francine D , Gray Timothy K
Published: December 2014

1. Metabolic and endocrine investigations were undertaken in a patient with acromegaly, diabetes mellitus, and hyperlipemia.

2. “Milky serum” disappeared with insulin therapy and diabetic control.

3. No abnormality in serum lipids or lipoprotein patterns was produced despite excess plasma growth hormone, excess adrenal corticosteroids, and the administration of fat or carbohydrate loads as long as rigid diabetic control was maintained.

4. Insulin deficiency was shown to be the major factor responsible for the hyperlipemia that occurred in this diabetic patient with active acromegaly.
Effects of Streptozotocin in a Patient with Islet Cell Carcinoma
Authors: Sadoff Leonard
Published: December 2014

Streptozotocin, a new antitumor agent with diabetogenie properties, was administered to a patient with functioning islet cell carcinoma. Tumor regression occurred and hypoglycemic symptoms disappeared. Drug-related renal and hepatic toxicity is discussed.
Effects of Starvation on Plasma Pancreatic Glucagon in Normal Man
Authors: Aguilar-Parada E , Eisentraut Anna M , Unger Roger H
Published: December 2014

The role of pancreatic glucagon in starvation has been difficult to assess in humans because of the nonspecificity of antisera heretofore available for glucagon radioimmunoassay. The development of a relatively specific antispnim for pacreation glucagon has now made possible valid measurements of pancreatic glueagun in human plasma and the effect of total starvation on plasma glucagon was, therefore, re-examined. Ten healthy male volunteers abstained from food for seventy-two hours or longer. During this period the mean level of glucose declined from 86 to 70 mg./100 ml., insulin declined from 10 to 3 μ./ml., while glucagon rose progressively from a mean prestarvation level of 126 μμg./ml. to 157, 189, and 178 μμg./ml. at the end of one, two, and three days' starvation, respectively. The responsiveness of the alpha cells to arginine stimulation was tested at the end of the starvation period by means of a forty-minute infusion of arginine at a rate of 11.5 mg./kg./min. Every one of the five subjects tested exhibited a prompt rise in glucagon secretion which reached a peak of 516 μμg./ml. in thirty minutes, significantly greater than the glucagon response of fed controls. Mean insulin concentration during the arginine infusion rose only 6.8 μU./ml. in contrast to a 29 μU./ml. rise in fed subjects. The biologic effect of the modest rise (about 50 per cent) in glucagon concentration would be exaggerated by the concomitant decline in insulin concentration. The magnitude and promptness of the gjucagon response to arginine suggests that the pancreas contains abundant glucagon after three days of total starvation.
Diabetes, Hyperglycemia and Glycosuria Among Indians, Malays and Africans (Bantu) in Cape Town, South Africa
Authors: Marine N , Vinik A I , Edelstein Isobel , Jackson W P U
Published: December 2014

Whole representative groups or randomly selected samples of Indians (of Asian origin) (1,520), Malays (1,252) and African Bantu (1,029) living in the Cape Town area were interviewed by social workers and screened by urine and blood sugar estimations after either a heavy meal or 50 gm. of glucose. Subjects who “screened positive” were subjected to full glucose tolerance tests, on which the final diagnosis of “discovered diabetes” was based. The screening methods used were of approximately comparable sensitivity,and the two sexes were almost equally represented in each age group and race.

The difference between postprandial and post-glucose blood sugar was not consistent, and rose with age. The meanscreening blood sugar levels of adults rose with age, but in young adults it was no higher than in children. There was no difference between the sexes, except apparently in the Malays. Africans had the lowest and Malays the highest mean blood sugar levels at all ages. (Known diabetics were excluded from these observations.)

The known diabetes rate among Indians was 4 per centover age fifteen, or 10.2 per cent when age-corrected. This is one of the highest prevalence rates known. Known diabetes (0.9 per cent) among the Africans was very similarto that usually reported among white populations. The total (known and discovered) diabetes prevalence among Indians was 10.4 per cent over age fifteen, rising to 60 per cent in women over fifty-five; among Africans it was3.6 per cent over age fifteen, with more diabetes in middleaged than in elderly people. Among the Malays the prevalenceof diabetes was intermediate (6.6 per cent over age fifteen).

Comparisons with other reported prevalence rates are extremely difficult because of great discrepancies due to differences in methods and interpretation. Thus whenever glucose loads and blood sugar estimations are used for screening, the prevalence is comparatively high; it is also high when a single blood glucose level is used for diagnosis.

Juvenile diabetes was rare; we found no known diabetic under age twenty and no African diabetic under thirty-five. Two seventeen-year-old Malay girls and one fifteen-year-old Indian were discovered to have asymptomatic diabetes.

Glycosuria was rare under age fifteen; it is argued thatthe renal threshold may fall with age. Glycosuria prevalence rose with age and was more common in men than women. The presence of glycosuria even after glucose was inconsistent. Glycosuria after glucose was more frequent than after a meal; among the Indians, postprandial glycosuria screening would have missed two thirds of the discovered diabetics, whereas all but one had glycosuria after glucose. Ninety-one per cent of the total newly discovered diabetics had glycosuria at one or another time of testing
Hyperglycemic, Nonketotic Coma Following Administration of Dilantin (Diphenylhydantoin)
Authors: Goldberg E Marshall , Sanbar Shafeek S
Published: December 2014

Two critically ill patients are described in whom the intravenous administration of Dilantin produced marked alterations in plasma glucose and blood pressure. The first patient, a nondiabetic with chronic lung disease received a total of 1.8 gm. Dilantin over a 48-hr, period for status epilepticus. Plasma glucose increased from normal to 1,200 mg./100 ml. and his seizures became focal in nature. The second patient, a mildly diabetic male, experienced renal shut-down and multiple arrythmias after a myocardial infarct. Three hours after a single intravenous injection of 200 mg. Dilantin, plasma glucose rose from 400 mg. to 1,260 mg./100 ml. and proved relatively resistant to insulin. Intravenous administration of 25 mg. Dilantin per kg. in four dogs promptly induced marked hyperglycemia and hypotension.
Ultrastructure of Capillaries in South African Diabetics: II. Muscle Capillaries
Authors: Yodaiken Ralph E , Seftel Harold C , Kew Michael C , Lillenstein Mark , Ipp Eli
Published: December 2014

A “blind” study on the ultrastructure of muscle capillaries has been carried out on diabetic and nondiabetic South African patients. A significant difference was found in the mean thickness of the basal lamina between the two groups. However, there was considerable overlap in the distribution of mean basal lamina thickness. Attention is drawn to the problems associated with measuring the basal lamina accurately, and to the need for making selective measurements around the circumference of the capillary. It is concluded that thickening of the basal lamina is nonspecific. Therefore, the study of muscle capillaries at this time does not appear to provide a means of diagnosing or prognosticating the course of the disease.
Glutathione-Insulin Transhydrogenase of Human Kidneys
Authors: Varandani P T , Nafz Mary Ann
Published: December 2014

Data are presented which show that an enzyme having properties very similar to those of glutathione-insulin transhydrogenase of liver occurs in human kidneys. The enzyme has been purified partially and some of its properties are described.
Relationship between Obesity, Chemical Diabetes and Beta Pancreatic Function in Children
Authors: Chiumello Giuseppe , Guercio Maria Jose Del , Carnelutti Margherita , Bidone Giovanni
Published: December 2014

Seventy-nine children, aged two and one-half to thirteen years, divided into four groups on the basis of their weight and family history of diabetes mellitus (one sibling or one parent with insulin dependent diabetes), were examined. The data showed that the occurrence of chemical diabetes was higher in children with family history of diabetes. In obese children hyperinsulinism was present, but glucose intolerance was associated with impairment of insulin secretion. The findings suggest that there probably is a genetically predisposed incapacity of beta cells to respond to various stimuli, and diabetes may develop in the face of relative insulin deficiency, regardless of the, absolute value of plasma insulin.
Absence of Glucose Response to Physiologic Levels of Serum Insulin
Authors: Meade Robert C , Kneubuhler Hans A , Barboriak Joseph J , Schulte William J
Published: December 2014

Insulin was given by intravenous injection and infusion into a peripheral vein of dogs to simulate the serum insulin levels obtained following pancreozymin or an intravenous glucose load. A significant change in free fatty acids was obtained without any change in serum glucose. A similar result was obtained by portal vein instillation of insulin. Pancreozymin plus intravenous glucose caused a much higher serum insulin concentration than glucose alone. However, the glucose turnover was the same. It is suggested that the causal relationship of insulin and glucose should be re-evaluated. Hyperinsulinemia in response to hyperglycemia may not be directly related to glucose homeostasis.
Metabolic Homeostasis in Juvenile Diabetes Mellitus: II. Increased Ketone Responsiveness to Epinephrine
Authors: Baker Lester , Kaye Robert , Hague Nasir
Published: December 2014

A series of epinephrine infusions were performed to study the possible role of catecholamines in the observed metabolic lability of juvenile diabetics. The data obtained in twenty insulin dependent juvenile diabetics were compared with the results obtained in eleven normal children.

Glucose and free fatty acid concentrations rose sharply in the diabetic group at the start of the epinephrine infusion, despite initial concentrations that were markedly elevated. The most striking difference between the diabetic children and the normal group, however, was seen in the blood ketone response. There appeared to be an increased ketone responsiveness to epinephrine stimulation in the diabetic child documented by the rate and magnitude of the ketone elevation, and by the absence of any lag period between the start of the epinephrine infusion and the rise of the blood ketone concentration.

Increased ketone responsiveness to epinephrine would appear to be an important characteristic of the juvenile diabetic. The ketone rise can be blocked by acute beta adrenergic blockade, indicating the dependence of the ketone rise on free fatty acid mobilization. The possible importance of hepatic triglycerides in diabetic ketosis is discussed.
Oral Administration of D-Ribose in Diabetes Mellitus
Authors: Steinberg Terry , Poucher Russell L , Sarin Raj K , Rees Richard B , Gwinup Grant
Published: December 2014

Thirty-four subjects were categorized on the basis of their glucose tolerance as normal (thirteen subjects), probable diabetics (six subjects), mild diabetics (five subjects), tolbutamide-responsive diabetics (five subjects) and insulin-dependent diabetics (five subjects). Fifteen grams of d-ribose dissolved in six ounces of water were administered orally to each of the subjects and the effect on serum glucose concentration was measured. The hypoglycemie effect of d-ribose varied in an orderly and progressive manner through the different categories of glucose intolerance. As their glucose intolerance increased in severity, the subjects were significantly less responsive to the blood glucose lowering effect of d-ribose.

The serum immunoreactive insulin concentration in response to the oral administration of d-ribose was measured in the normal and mild diabetic subjects. The mild diabetics had a mean peak increase in immunoreactive insulin which was 2.6-fold greater than the normal subjects; however, the insulin concentrations attained were not significant in either group. Thus the insulinogenic response as determined in peripheral venous blood does not account for the differential hypoglycemie effect of d-ribose.
Plasma Insulin Concentrations in Dogs and Monkeys After Xylitol, Glucose or Tolbutamide Infusion
Authors: Wilson Robert B , Martin Julio M
Published: December 2014

Beagle dogs and Rhesus monkeys were infused with xylitol, glucose, or tolbutamide at intervals of ten to fourteen days. Infusion of all three agents produced significant increases in mean plasma insulin concentrations in both species. In dogs, xylitol produced the highest insulin concentrations followed by glucose and tolbutamide in that order, while in monkeys, glucose produced the highest insulin concentrations followed by tolbutamide and xylitol. The insulinotropic effect of both xylitol and glucose in the monkey was abolished by simultaneous infusion of epinephrine. Results suggest that glucose and xylitol stimulate release of insulin through a common metabolite of the pentose phosphate pathway. However, unexplained quantitative differences exist between the monkey and dog with respect to the insulinotropic response to these agents.
Hormonal Changes During Ribose-induced Hypoglycemia
Authors: Ginsburg Jean , Boucher Barbara , Beaconsfield Peter
Published: December 2014

Plasma levels of insulin and human growth hormone (HGH) were measured in healthy adults after oral or intravenous administration of the pentose sugar D-ribose. Increased plasma levels of insulin were recorded after both oral and intravenous ribose; there was no consistent change in plasma levels of HGH after administration of ribose by either route. It is suggested that insulin release occurs at such times and in amounts as may account at least in part for the hypoglycemie effect of this pentose.
Lactate Turnover and Gluconeogenesis in Obesity: Effect of Phenformin
Authors: Kreisberg R A , Pennington L F , Boshell B R
Published: December 2014

The effect of phenformin on the rates of lactate and glucose turnover, interconversion, and oxidation was determined in five obese subjects with normal glucose tolerance. L (+) lactate-U (50 μc.) and glucose 1-C-14 were administered over four-hour periods on consecutive days by a primed infusion technic. One hundred to 150 mg. of phenformin was administered daily, and the turnover studies were repeated on the sixth and seventh days of therapy. Phenformin increased glucose turnover by 10 per cent, from 95.6 ± 4.4 to 106.2 ± 4.7 (mean ± S.E.M.) mg,/kg./ hr. and glucose recycling by 100 per cent, from 8.7 ± 1,4 to 19.3 ± 1.3 mg./kg./hr. In contrast, the changes in glucose oxidation were inconsistent, decreasing in three subjects and increasing in two. As expected, the blood glucose concentration and glucose pool were unchanged during treatment with phenformin. Lactate turnover increased 30 per cent, from 63.5 ± 3.5 to 82.8 ± 5.7 mg./kg./hr., and lactate derived from glucose (glucose conversion to lactate) increased 25 per cent, from 57.9 ± 5.5 to 71.8 ± 6.9 mg./kg./hr. Lactate conversion to glucose increased in all subjects by a mean of 13.1 ± 1.2 mg./kg./hr., from 15.2 ± 1.2 to 28.2 ± 1.8 mg./kg./hr. The increase in lactate conversion to glucose was almost identical to the increase in glucose turnover and glucose conversion to lactate. During therapy with phenformin, 34.1 ±1.2 per cent of the lactate turnover was converted to glucose in contrast to 22.1 ± 1.3 per cent before therapy. These results demonstrate that phenformin enhances the interconversion of glucose and lactate in subjects in whom it exerts no hypoglycemie effect.
Skin Acidic Glycosaminoglycans in Alloxan Diabetic Rats
Authors: Kofoed J A , Bozzini C E , Alippi R M
Published: December 2014

Rats made diabetic by administration of alloxan showed a 36 per cent reduction in total GAG concentration. The concentration of hyaluronic acid was 59 per cent and that of chondroitin-4-sulfate 40 per cent decreased. Heparin concentration was 51 per cent increased. The other sulfated fractions did not appear to be affected. The administration of insulin almost entirely restored the level of the affected GAG to normal values, with the only exception of heparin.
Comparison of the 50 and 100 Gram Oral Glucose Tolerance Test
Authors: Sisk Charles W , Burnham Clinton E , Stewart John , McDonald Glen W
Published: December 2014

A series of two 100 gm. and two 50 gm. oral glucose tolerance tests were performed on each of ninety-six young, healthy, prison inmates under rigidly controlled experimental conditions. Mean blood glucose levels for fasting, one, two, and three hour-postchallenge determinations were compared between challenges. The interrelationships of these determinations were also compared between the two standard loading doses.

Mean two-hour levels were 14 to 27 per cent higher after the larger challenge. With an appropriate conversion factor, the absolute difference in two-hour values could be equated. Thus, despite these unequal means, the diagnostic information obtained with either challenge at one and two hours does not differ. The fact that the one-hour determination was not related to loading dose size or obesity as expressed by the weight index [100 (weight)/height2] and was highly correlated with the Tolerance Index, suggests that it is the preferable screening test for diabetes. Studies in other populations are needed to confirm this, however.

Although mean levels at three hours were the same, the distribution of tolerance responses for this determination differed for the two challenges. An excess of both relative hypoglycemic andhyperglycemic responses occurred with the larger loading dose. These contrasting distributions suggest that the 100 gm., three-hour determination may possess unique diagnostic power to ascertainearly chemical diabetes. Until adequate criteria of an abnormal three-hour response are established, however, this determination cannot be used as a screening test for diabetes.

Physiologic variability for all specific determinations and the complete tolerance test were similar for both challenges. The fact that only a moderate degree of correlation was found between repeat tolerance responses greatly compromises the clinical values of a single glucose tolerance test.
Effects of Fasting and Hypophysectomy on FFA Uptake and Ketone Body Production by the Isolated, Perfused Rat Liver
Authors: Clark Charles M , Scow Robert O
Published: December 2014

The effect of fasting overnight and hypophysectomy on free fatty acid (FFA) uptake and ketone body production by isolated, perfused rat livers was investigated. FFA uptake was directly related to FFA concentration over a wide range of concentrations (0.31 to 2.41 mM) in both fed and fasted rats. Whereas ketone body production increased with FFA uptake, it was greater at any given FFA concentration in livers from overnight fasted than in livers from fed donors. The relationship between FFA concentration and FFA uptake was unaltered by hypophysectomy. At low FFA concentrations livers from fed hypophysectomized rats demonstrated an increased rate of ketone bodyproduction as compared to those from fed normal rats. Livers from hypophysectomized rats fasted overnight produced ketone bodies at an increased rate as compared to livers from fed hypophysectomized rats, but the difference was significant only at high FFA concentrations.
Glycoprotein Changes in Diabetic Kidneys
Authors: Srinivasan S R , Berenson G S , Radhakrishnamurthy B
Published: December 2014

A study of glycoproteins from renal cortical tissue from seventeen individuals with diabetes mellitus and four controls was performed. The diabetic tissues were divided, based on observations of the acid mucopolysaccharide composition from an earlier study, into three groups: seven showed a milder clinical course of diabetes and minimal histologic changes; five had severe clinical diabetes and predominantly nodular Kimmelstiel-Wilson lesions; and the remaining five had moderate to severe clinical diabetes with predominantly diffuse intercapillary glomerulosclerosis. In the latter two groups, a marked increase of neutral sugars was noted, particularly suggesting an increase in galactose-containing glycoprotein. Similarly, shifts to electrophoretically faster-moving glycoproteins and more intense PAS'staining were noted in severe diabetic changes. These observations suggest that there may be significant chemical changes in the nature of glycoproteins asociated with diabetes which may reflect on an uncontrolled metabolic defect of this disease.
Glucose Tolerance in Man during Chlorpromazine Therapy
Authors: Waitzkin Leo
Published: December 2014

Neither brief nor long chlorpromazine therapy appears to impair carbohydrate tolerance in hospitalized, mentally ill men under fifty yėars of age, as measured by a 100-gm., three-hour, oral glucose tolerance test.
Beta Adrenergic Receptor Mechanisms in the Metabolic Effects of Diazoxide in Fasted Rats
Authors: Walfish Paul G , Natale Renato , Chang Catherine
Published: December 2014

The role of beta adrenergic receptor mechanisms in the metabolic effects of diazoxide was assessed in anesthetized fasted or partially refed rats using the beta blocker pro-pranolol. The prior administration of propanolol significantly inhibited the expected diazoxide-induced increases in blood sugar, plasma lactate and glycerol. Also, propranolol blockade of diazoxide hyperglycemie was more effective in fasted than partially refed rats. It was concluded that diazaxide hyperglycemia in fasted rats is accompanied by increases in plasma lactate and glycerol as a consequence of beta adrenergic receptor stimulation. These observations indicate that extrapancreatic beta receptor catecholamine factors are important in diazoxide-induced hyperglycemia and support the theory for at least a partial role of catecholamine mechanisms in the metabolic effects of diazoxide.
Inhibition of Glucose Oxidase Paper Tests by Reducing Metabolites
Authors: Feldman Jerome M , Kelley William N , Lebovitz Harold E
Published: December 2014

A negative urinary glucose oxidase test in the presence of glucbsuria may occur in patients with alcaptonuria or the carcinoid syndrome. It may also be noted after ingestion of aspirin or L-dopa. The responsible agents are potent reducing metabolites such as gentisic acid, homogentisic acid, or 5-hydroxyindole acetic acid. These agents produce the misleading reaction by keeping the indicator dye o-tolidine in its reduced form. In the presence of such reducing agents the tests for glucosuria should be carried out either with Tes-Tape or by modifying the manufacturer's instructions and only partially immersing the Clinistix strip.
Influence of Obesity on the Relationship Between Insulin and Triglyceride Levels in Endogenous Hypertriglyceridemia
Authors: Bagdade John D , Bierman Edwin L , Porte Daniel
Published: December 2014

In order to assess the influence of obesity on the relationship between insulin and triglyceride levels, basal plasma triglyceride (TG) and immunoreactive insulin (IRI) levels prior to and during oral glucose (100 gm.) tolerance tests were compared in nonlipemic control subjects and patients with endogenous hypertriglyceridemia with comparable glucose tolerance. Basal IRI and body weight correlated closely in both lipemic (r = +.75, p < .001) and nonlipemic groups (r = +.72, p < .001), and no significant increase in basal IRI was observed in the lipemic subjects when matched for weight.

In both lipemic and control groups basal IRI and TG levels were related to a comparable degree (r = +.44, p < .01); however, for any given basal IRI, TG levels in the lipemic group were dramatically increased. No relationship was demonstrable between TG and stimulated IRI levels expressed either as absolute increments or when the effects of obesity on insulin secretion were excluded by expression of each insulin response to glucose as a percentage of the basal level.

In both groups, glucose intolerance and the per cent increment in IRI at both sixty and 180 min. were inversely related, and when matched for glucose tolerance, no quantitative difference in stimulated IRI levels was demonstrable in patients with endogenous hypertriglyceridemia and the control group. When factors such as glucose intolerance have been controlled, variations in IRI are best explained by variations in body weight.

These findings indicate that the high IRI levels often observed in patients with endogenous hypertriglyceridemia result from coexisting obesity.
Patterns of Serum Immunoreactive Human Placental Lactogen (IR-HPL) and Chorionic Gonadotropin (IR-HCG) in Diabetic Pregnancy
Authors: Selenkow Herbert A , Varma Kamlesh , Younger Donna , White Priscilla , Emerson Kendall
Published: December 2014

Serum levels of immunoreactive human placental lactogen (IR-HPL) and chorionic gonadotropin (IR-HCG) were evaluated in eighty-four diabetic patients classified according to White. All patients in this group were treated with estrogen/progesterone therapy throughout pregnancy and were compared with a small group of twenty-seven diabetic patients not receiving hormonal therapy. In 164 normal pregnancies, serum IR-HPL is detected first at about six weeks and rises steadily to plateau levels of 6.2 ± 1.4 μg./ml. at thirty-five to thirty-seven weeks. In eighty-four diabetic pregnancies, the pattern of steady rise in IR-HPL levels simulates normal but the mean values are significantly greater than normal with peak values of 10.3 ± 4.7 /μg./ml. at thirty-five to thirty-seven weeks. Serum IR-HCG is first measured in normal pregnancy at about five to seven weeks by this assay, rises rapidly to peak levels of 163 ± 60 IU./ml. at eight to ten weeks and then falls to a nadir of 12.0 ± 2.0 IU./ml. at seventeen to nineteen weeks. Thereafter, there is a gradual secondary rise to a lesser mean peak value of 63 ± 19 IU./ml. at thirty-five to thirty-nine weeks. In diabetic pregnancy, the pattern of serum IR-HCG is similar to normal but with striking quantitative differences. The mean values in the second and third trimesters are significantly higher than normal with extreme variations among different pregnant individuals. The clinical implications of these abnormalities are not clear but suggest that the excessive secretion of HCG may mollify the diabetic imposition of early pregnancy whereas HPL contributes to the exaggerated glucose intolerance in late pregnancy.
Diabetes in the Pima Indians: Evidence of Bimodality in Glucose Tolerance Distributions
Authors: Rushforth Norman B , Bennett Peter H , Steinberg Arthur G , Burch Thomas A , Miller Max
Published: December 2014

Venous plasma glucose levels two hours after a 75 gm. carbohydrate load were determined on over 2,900 Pima Indians, a population known to have an extremely high prevalence of diabetes mellitus. In each sex and in each decade above twenty-five years of age, the frequency distributions of the logarithms of the glucose levels were clearly bimodal, but below this age a single symmetrical unimodal distribution was found. A maximum likelihood procedure was used to derive the best fitting theoretical gaussian distributions for each group of data, together with the parameters of each distribution.

The observed bimodal distributions were found to be in satisfactory agreement with a model of two overlapping gaussian distributions, indicating that a logical separation between those with normal and high levels of glucose is possible, although the presence of overlap indicates that some misclassification will occur if any finite level is used to subdivide the population.

The data indicate that among the Pima: 1. The frequency distributions of two-hour glucose tolerance levels can be used to identify objectively and describe a hyperglycemic population without recourse to other criteria for diabetes. 2. There are small changes in the parameters of “normal” glucose tolerance between the ages of twenty-five and sixtyfour years. 3. The increase in mean glucose level found with rising age in this population is mainly the result of an increasing proportion of subjects who are in the group characterized by marked glucose intolerance.

The bimodal distributions of plasma glucose levels The bimodal distributions of plasma glucose levels among the Pima Indians contrast with those described so far in other groups. It seems likely that differences are attributable to the lower prevalence of diabetes elsewhere which would obscure the identification of bimodality.
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.
Evaluation of the Liver Adenosine 3′,5′-Monophosphate Response to Glucagon
Authors: Pauk G L , Reddy W J
Published: December 2014

Basal levels of adenosine 3′, 5′-monophosphate (c-AMP) and the accumulation of c-AMP in liver in response to intravenous glucagon administered to Sprague-Dawley rats were studied in various states of nutrition, adrenal function and drug treatment. No major difference was observed in basal levels of c-AMP in fed and fasted rats. Glucagon produced a much greater rise in c-AMP in livers of fasted than fed rats. Refeeding the fasted rats for twenty-four hours decreased the response to glucagon; however, refeeding for three hours did not significantly change the increased responsiveness. L-tryptophan, but not tyrosine, pretreatment for three hours of the fasted rat produced a marked decrease in the response to glucagon. Adrenalectomy produced a decreased response of liver c-AMP to glucagon which was restored toward normal by cortisone treatment. The response of the liver to glucagon was markedly decreased by dihydroergotamine but not changed by dichloroisoproterenol or propranolol. Changes in blood glucose were in the same direction as changes in c-AMP but there was no close correlation.
Purification and Characterization of a Protease with Specificity for Insulin from Rat Muscle
Authors: Brush James S
Published: December 2014

A soluble enzyme partially purified from rat muscle is described which degrades insulin proteolylically with a high degree of specificity. The enzyme attacked proinsulin and proinsulin intermediates at only 3 per cent and 10 per cent of the rate with insulin, respectively. Proinsulin competitively inhibited insulin degradation with an inhibition constant of 0.28 μM, whereas the Km for insulin was 0.18 μM. Insulin derivatives with amino or carboxyl terminal residues removed were attacked with Km's about five times greater. Removal of an octapeptide from the B chain of insulin resulted in a Km the same as for insulin. The enzyme is inhibited by the sulfhydryl reagents, N-ethylmaleimide and p-hydroxymercuribenzoate, but not by an inhibitor of the pancreatic proteases, phenylmethylsulfonyl fluoride. The enzymatic activity was not inhibited by a large excess of a number of other proteins and polypeptide hormones. These results suggest that the enzyme is a sulfhydryldependent protease which is quite specific for insulin, parameters studied.
Plasma and Pancreatic Insulin Concentrations in Adult Squirrel and Rhesus Monkeys
Authors: Wilson Robert B , Martin Julio M , Kelly Heather , Newberne Paul M
Published: December 2014

Squirrel and rhesus monkeys were given oral glucose (4 gm./kg.), intravenous glucose (0.4 gm./kg.), intravenous glucose and tolbutamide (0.4 gm./kg. glucose and 50 mg./kg. tolbutamide), or intravenous tolbutamide (15 and 50 mg./kg.). There was delayed disposal of the relatively large doses of orally administered glucose in squirrel monkeys, contrasted with rhesus monkeys. Differences in glucose metabolism between the two species were less apparent during the other tests. Concentrations of plasma -insulin were significantly lower in squirrel than in rhesus monkeys during all of the stimulatory tests, except during the infusion of the lower dose of tolbutamide, when levels in both were relatively low. In contrast, pancreatic islet morphology and concentrations of pancreatic insulin did not differ significantly between the two groups, suggesting that differences in plasma insulin concentrations during stimulatory tests might have been the result of differences in insulin secretory rates. In our group of squirrel monkeys, we could not recognize two populations with respect to any of the parameters studied.
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.
Effects of Gestational Age, Birth and Feeding on the Insulinogenic Response to Glucose and Tolbutamide by Fetal and Newborn Rat Pancreas
Authors: Sodoyez-Goffaux Francoise , Sodoyez Jean-Claude , Foá Piero P
Published: December 2014

Perinatal maturation of the pancreatic beta cells was studied in the rat. Insulin synthesis proceeded rapidly be tween the twentieth gestational day and the third postnatal day. The insulin concentration in the pancreas and the amount of insulin available per gram of body weight reached a maximum sixty hours after birth and then decreased slowly toward the values observed in the adult rat. The pancreatic beta cells became responsive to glucose and to tolbutamide during the twenty-third day after fertilization, This phenomenon seemed to be related to the gestational age and not to act of birth or to feeding, although feeding appeared to increase the insulinogenic response to glucose.
Perifusion of Isolated Rat Islets in Vitro: Participation of the Microtubular System in the Biphasic Release of Insulin
Authors: Lacy Paul E , Walker Mary M , Joan Fink C
Published: December 2014

A simple perifusion system for in vitro studies on the rate of insulin secretion of isolated rat islets is described. A biphasic pattern of insulin secretion was produced by glucose whereas tolbutamide stimulated only the first phase of insulin secretion. The perifusion system was used to determine the effect of anti-mitotic agents on the biphasic pattern of insulin secretion. Yinblastine and colchicine destroy microtubules whereas deuterium oxide (D2O) produces stabilization and interference with the function of microtubules. Vinblastine (10-4 M) and D2O (100 per cent) inhibited completely the first and second phase of glucose-induced insulin secretion. The inhibitory effect of D2O was reversible and a biphasic pattern of secretion occurred following the replacement of D2O with water. Colchicine (10-3 M) produced significant inhibition of only the second phase of glucose-induced insulin secretion. The first phase of tolbutamide-induced insulin secretion was inhibited by vinblastine and D2O and the inhibitory effect of D2O was reversible. Colchicine did not inhibit the first phase of tolbutamide-induced insulin release. These findings indicate that the microtubular system is involved in both phases of insulin secretion. The first phase of secretion may be due to the release of beta granules already associated with the microtubular system and the second phase could be the result of stored and newlysynthesized granules becoming associated with the system.
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 < 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 > 0.05), while the activity was significantly (P < 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 < 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.
Antilipolytic Action of Insulin on Fat Cells
Authors: Fain John N , Rosenberg Leon
Published: December 2014

The hypothesis that the effects of insulin on adipose tissue metabolism are secondary to inhibition of cyclic AMP accumulation was investigated using isolated rat white fat cells. No effect of incubation with insulin on the subsequent adenyl cyclase activity of fat cell ghosts or on phosphodiesterase activity of the high speed supernatant from homogenates of white fat cells was seen. Under conditions in which insulin inhibited the lipolytic action of catecholamines it did not affect the accumulation of total cyclic AMP, labeled cyclic AMP or ATP in white fat cells. The stimulation of leucine incorporation into protein and of [1-14C] glucose oxidation by insulin was abolished by high concentrations of theophylline. However, in the presence of an amount of norepinephrine which gave a 75 per cent maximal stimulation of lipolysis the increase in leucine incorporation into protein and glucose oxidation due to insulin was actually enhanced. The addition of theophylline to cells incubated with norepinephrine abolished the antilipolytic and other actions of insulin. The addition of dibutyryl cyclic AMP or fatty acids mimicked the effects of lipolytic agents on insulin action except that fatty acids stimulated lactate formation. The inhibition by high concentrations of lipolytic agents on the stimulation by insulin of glucose metabolism and leucine incorporation into protein appears to be due to accumulation of intracellular free fatty acids. Our results suggest that the antilipolytic action of insulin may also be unrelated to effects of insulin on cyclic AMP accumulation.
Relationship of Some Hepatic Actions of Insulin to the Intracellular Level of Cyclic Adenylate
Authors: Park C R , Lewis S B , Exton J H
Published: December 2014

Glucagon and/or the catecholamines elevate tissue cyclic adenylate (cAMP) and thereby change the activity of a number of metabolic processes, as studied in the isolated perfused rat liver. Insulin can lower cAMP in liver and thereby opposes these changes. In liver, in the basal state, there appears to be a substantial quantity of cAMP which is compartmentalized, unaffected by insulin and physiologically inactive. The hormone effects are exerted on a pool of “free cAMP,” and changes in the level of this pool control the minute-to-minute output of glucose and presumably effect rapid regulation of potassium fluxes and other processes. The level of cAMP in the active pool in the perfused liver is reflected by the efflux of the nucleotide into the medium. Not all insulin effects in liver or other tissues are mediated by a fall in cAMP.