bluuebunny/crossref_metadata_2025 huggingface dataset:
Defective Insulin Secretory Response to Glucose in the New Zealand Obese Mouse: Improvement with Restricted Diet
Authors: Larkins R G
Published: December 2014

Insulin and glucose tolerance tests, and tests of the plasma insulin response to injected glucose were compared in C57B ad libitum fed mice (control strain), NZO ad libitum fed mice, C57B mice with obesity due to induced hyperphagia following gold thioglucose administration, and NZO mice whose weight had been reduced to that of the control strain by dietary restriction. The ad libitum fed NZO mice showed impaired glucose tolerance, increased insulin resistance, basal hyperinsulinemia arid absent rise in plasma insulin in response to glucose injection. The gold thioglucose-treated mice also showed impaired glucose tolerance and insulin resistance, but they demonstrated a rise in plasma insulin in response to glucose injection. The NZO mice whose diet had been restricted showed variable glucose tolerance, improved but not normal insulin sensitivity, and a significant rise in plasma insulin in response to injected glucose. It is concluded that thepancreatic islets of obese NZO mice, although very responsive to arginine, are insensitive to glucose, and with- weight reduction sensitivity to glucose returns.
Effect of Dehydration and Hyperosmolarity on Glucose, Free Fatty Acid and Ketone Body Metabolism in the Rat
Authors: Gerich John , Penhos Juan C , Gutman Raul A , Recant Lillian
Published: December 2014

The effect of water deprivation was studied in rats fasted twenty-four, forty-eight and seventy-two hours. Glucose tolerance was impaired and insulin levels were lower one hour after an intraperitoneal glucose load. Ketone bodies (KB) and free fatty acid (FFA) levels were significantly lower. FFA rise after epinephrine was reduced. Hypertonic mannitol (3 M) administered subcutaneously to fasted rats also resulted in glucose intolerance and decreased levels of FFA and KB. In vitro hyperosmolarity(50, 100 mOsm. per liter mannitol) reduced FFA release from rat epididymal fat pads and impaired pancreatic insulin response to glucose. No effect on ketone body production by perfused rat liver was found. It is postulated that the above metabolic effects of dehydration and hyperosmolarity may be involved in the pathogenesis of hyperosmolar nonketotic coma in patients.
Histocompatibility (HL-A) Antigens, Lymphocytotoxic Antibodies and Tissue Antibodies in Patients with Diabetes Mellitus
Authors: Singal D P , Blajchman M A
Published: December 2014

Diabetes mellitus is a genetically determined disorder of metabolism in which inherited susceptibility plays an important part. We studied the distribution of HL-A antigens, and theincidence of lymphocytotoxic and tissue antibodies in seventy-one adult diabetic patients—fifty insulin-dependent and twenty-one insulin-independent. Specificity W15 was present in significantlyhigher frequency in the insulin-dependent diabetic patients than either in the control group (P = 0.0005) or in the insulin-independent diabetic patient group (P < 0.0005). The incidence of lymphocytotoxic and tissue antibodies in the two patient groups was not different from that in the control population.
Spontaneous Hypoglycemia Associated with Chronic Renal Failure
Authors: Frizzell Marilyn , Larsen P Reed , Field James B
Published: December 2014

Spontaneous, prolonged hypoglycemia was observed in one nondiabetic and one mildly diabetic patient, both with chronic renal insufficiency. Although both patients had abnormal oral glucose tolerance tests, half-time disappearance of glucose was usually normal during intravenous glucose tolerance tests. Both patients developed persistent hypoglycemia during the tolbutamide tolerance test, but the insulin responses were not consistent with an islet cell adenoma. The hypoglycemia did not seem to reflect increased insulin secretion, increased insulin sensitivity or impaired glycogenolysis as assessed by the blood glucose response to glucagon. Although some factor associated with chronic renal disease was probably responsible for the hypoglycemia, the underlying mechanism was not defined.
Relationship Between Fasting Plasma Insulin Level and Resistance to Insulin-Mediated Glucose Uptake in Normal and Diabetic Subjects
Authors: Olefsky Jerrold , Farquhar John W , Reaven Gerald
Published: December 2014

We have previously shown that a significant inverse correlation exists between the height of the plasma insulin concentration and the efficiency of glucose uptake in the fasting state. Subsequently, we devised an infusion technic that provides a more specific measure of cellular resistance to insulin mediated glucose uptake. We have used this technic to study the relationship between fasting plasma insulin level and resistance to insulin mediated glucose uptake in twenty-two patients with normal oral glucose tolerance, fourteen patients with impaired glucose tolerance, and fourteen patients classified as having chemical diabetes mellitus. The results indicate a highly significant positive correlation between the degree of insulin resistance and fasting plasma insulin concentration (r = .69, p < .0001). A positive correlation (r = .43, p < .005) was also found between the degree of insulin resistance and the two hour plasma glucose level during an oral glucose tolerance test. However, no significant correlation was found between per cent adiposity and fasting insulin level, and the relationship between insulin resistance and fasting insulin level appeared to be independent of obesity or any other known cause of decreased insulin responsiveness. These studies indicate that: (1) increases in fasting insulin levels and increase in resistance to insulin mediated glucose uptake are closely related, and that these changes can occur in the absence of any of the “known” causes of decreased insulin responsiveness; (2) in the types of subjects we have studied, deterioration of glucose tolerance is closely related to increases in insulin resistance; and (3) the increases in fasting insulin levels which we have observed appear to be compensatory attempts to overcome the resistance to glucose uptake.
Electron Microscopic Quantification of Diabetic Microangiopathy
Authors: Siperstein Marvin D , Raskin Philip , Burns Henry , Ann Johnson Alice , Sill Mary Jo
Published: December 2014

1. Several methods of quantifying muscle capillary basement membrane width have been evaluated with the aim of determining whether variations in technic may influence the sensitivity of detecting significant capillary basement membrane thickening in diabetic subjects.

2. The results demonstrate that fixation of tissue in osmic acid followed by determination of mean basement membrane thickness reveals significant basement membrane thickening in over 90 per cent of diabetic subjects.

3. The error in estimation of mean basement membrane width due to oblique sectioning of diabetic capillaries is shown to be small, i.e. approximately 10 per cent. By contrast, measuring only the minimum basement membrane thickness of a capillary may underestimate diabetic basement membrane hypertrophy by from 20 to 40 per cent.

4. As compared to osmic acid fixation, glutaraldehyde leads to a very significant increase in the basement membrane width affecting normal capillaries relatively more than diabetic capillaries.

5. As a result, either fixation in glutaraldehyde or measurement of minimum basement membrane thickness may lead to a marked decrease in the sensitivity of the quantitative basement membrane technic. A procedure that employs both glutaraldehyde fixation and measurement of only minimum basement membrane width would appear to detect microangiopathy in only 45 per cent of diabetic subjects.
Glucose Intolerance with Hypokalemia: Failure of Short-term Potassium Depletion in Normal Subjects to Reproduce the Glucose and Insulin Abnormalities of Clinical Hypokalemia
Authors: Gorden Phillip
Published: December 2014

The mechanism by which potassium deficiency per se impairs glucose tolerance was studied in seven subjects who were potassium depleted experimentally (mean depletion = 326 mEq.).

In five subjects studied using the oral glucose tolerance test, all showed impairment during the potassium depletion phase compared to the predepletion control period, and four of five subjects showed improvement with potassium repletion. The four subjects with impaired glucose tolerance compared to both control periods showed a delay in the initial phase of total immunoreactive insulin release. None of the five subjects showed a significant variation in the per cent proinsulin-like component from the potassium depletion phase to either control period. Two subjects studied using the intravenous glucose tolerance test showed no impairment of glucose tolerance with potassium depletion, and no evidence of insulin resistance was found following the injection of 0.05 U. per kilogram of insulin. These two subjects did manifest impaired growth hormone responses to the hypoglycemic stimulus, however.

Potassium depletion per se impairs glucose tolerance. The defect is mild; severe glucose intolerance, alterations in total immunoreactive insulin, and plasma insulin components seen in clinical hypokalemic states involve a complex interplay between potassium deficiency and the primary disease state.
Fetal Rat Pancreas: Differentiation of the Acinar Cell Component in Vivo and in Vitro
Authors: McEvoy Robert C , Hegre Orion D , Leonard Robert J , Lazarow Arnold
Published: December 2014

Fetal rat pancreases, Day 16 through Day 22 postcoitum, were analyzed biochemically for amylase and chymotrypsinogen to assess acinar cell development in vivo. The interval between -eighteen and twenty days proved to be a critical period in the differentiation of the acinar component. Eighty- and thirtyfold increases in, respectively, amylase and chymotrypsinogen concentration were accompanied by a large increase in the acinar cell percentage of the pancreas.

Explantation of pancreas either before or after this critical period resulted in a developmental pattern which varied from that observed in vivo. The present organ culture system neither supported the differentiated acinar cell nor favored the further development of new acinar cells.

Using the present organ culture system, explants can be produced which are devoid of acinar cells and their exocrine enzymes.
Diabetic Retinopathy in Identical Twins
Authors: Pyke D A , Tattersall R B
Published: December 2014

The prevalence and features of diabetic retinopathy have been examined in twenty-three pairs of identical twins—thirteen concordant (both diabetic) and ten discordant (one diabetic, one not)—who have had diabetes for at least fifteen years. In the concordant pairs retinopathy was more common (present in twenty-three out of twenty-six individuals) and more severe (seven blind or partially sighted) and a family history of diabetes was more frequent than in the discordant pairs (retinopathy in five out of ten, none blind). In twelve out of the thirteen concordant pairs the progression and severity of retinopathy was strikingly similar in the two twins and was correlated only with the duration of diabetes. In the thirteenth pair after twenty years of diabetes, one was blind and the other had normal eyes, although they showed no obvious differences in control or other features. It seems that genetic factors may be important in the etiology and time of appearance of diabetic retinopathy.
Plasma Norepinephrine and Epinephrine in Untreated Diabetics, During Fasting and After Insulin Administration
Authors: Christensen Niels Juel
Published: December 2014

Employing a precise and sensitive double-isotope derivative technic, plasma norepinephrine and epinephrine were measured in twenty-three normal subjects and fourteen diabetics during various metabolic conditions. Patients with poorly controlled diabetes showed a rise in norepinephrine, which correlated with the degree of metabolic derangement, during resting conditions. High epinephrine values were seen only in patients with moderate to severe ketoacidosis. During exercise, diabetic patients with ketosis demonstrated large increments in plasma catecholamines as compared to normals. During insulin treatment, when good control had been achieved, plasma catecholaniine levels were similar to those in normal subjects.

During prolonged fasting, plasma norepinephrine rose from 0.18 to 0.40 ng. per milliliter in four normal nonobese subjects. No change was observed in plasma epinephrine.

During insulin hypoglycemia, high plasma epinephrine levels were seen only in subjects in whom the blood glucose concentration declined to values below 20 mg. per 100 ml. Plasma norepinephrine rose as blood glucose concentrations decreased even in diabetics in whom values had not reached hypoglycemic levels. No correlation was observed between plasma epinephrine and increase in pulse rate during hypoglycemia.
Urinary Excretion of n-Hexanedioic and n-Octanedioic Acid in Juvenile Diabetics with Ketonuria
Authors: Pettersen Jon Elling
Published: December 2014

Urine samples from patients with newly diagnosed juvenile diabetes and predibetic coma or ketonuria, but no acid-base disturbances in the blood, have been analyzed for dicarboxylic acids by combined gas-liquid chromatography and mass spectrometry.

The precomatose patients excreted up to 210 and 38 μg./1 mg. of creatinine, respectively, of n-hexanedioic and n-octanedioic acid. The excretion was almost normalized within a few hours by insulin treatment. Nonacidotic patients with ketonuria excreted 9.2 ± 5.1 mg./24 hr. of n-hexanedioic acid, and some also excreted slightly increased amounts of n-octanedioic acid. All patients excreted normal amounts of 3-methylhexanedioic acid, which was unaffected by insulin treatment.

Our findings direct attention to a metabolic pathway which may be of importance in the pathogenesis of ketosis in diabetes mellitus, namely the formation of short-chain dicarboxylic acids (for instance, intermediates of the tricarboxylic acid cycle) by ω-oxidation of fatty acids followed by β-oxidations of the dicarboxylic acids thus formed.
Insulin Response to Arginine in Normal Newborn Infants and Infants of Diabetic Mothers
Authors: King Katherine C , Adam Peter A J , Yamaguchi Kiyoko , Schwartz Robert
Published: December 2014

The effect of maternal diabetes during pregnancy on insulin release of the newborn infant was examined employing arginine infusion as stimulus. At age two hours, eight normal newborn infants, six of gestationally diabetic mothers (IGDM) and four of insulin-dependent diabetic mothers (IDM) were infused with arginine hyd-rochloride 0.5 gm. per kilogram body weight for thirty minutes. Eight additional normal newborn infants were infused with isotonic saline. A small but definite rise in plasma IRI was observed in the normal newborns receiving arginine; however, the infants of gestationally diabetic mothers responded with an enhanced blood glucose and plasma insulin rise compared with the normal newborns. It seemed that intermittent or sustained hyperglycemia in utero may have potentiated the neonatal insulin response to arginine.
Diabetes in American Indians and Other Native Populations of the New World
Authors: West Kelly M
Published: December 2014

This is a review of previous and more recent observations on the prevalence and manifestations of diabetes in aboriginal populations of the New World. Rates of diabetes have now been measured or estimated in more than eighty of these groups in the Americas, Greenland, Polynesia, Micronesia and Melanesia. Diabetes was probably uncommon in all these native populations prior to 1940. It is now rife in many of these groups, but still rare in many. Among certain of these populations, rates of diabetes in adults still differ more than tenfold. Among groups of diabetics there are probably significant intertribal differences in the susceptibility to certain manifestations and complications such as retinopathy and coronary disease. There appear to be peculiarities in the insulin secretion patterns of certain of these tribes.

The available evidence does not rule out the possibility that genetic factors play an important role in determining inter-tribal differences in prevalence and manifestations. But it is also clear that environmental factors exert powerful effects. Low rates of diabetes have been observed in Athapascan tribes and in some Shoshonean tribes. Diabetes was also rare prior to 1940 in Athapascan and Shoshonean Indians of Oklahoma. But diabetes has recently become common in these Oklahoma tribes. They were formerly lean and are now fat. The status of the many Oklahoma tribes is of particular interest because they represent seven of the eight major linguistic groups of North American Indians, having originated in very diverse parts of the Continent. Rates are now high in all Oklahoma tribes for which evidence is adequate to permit an estimate of prevalence. This includes fifteen tribes drawn from seven different linguistic groups. In seven additional Oklahoma tribes preliminary evidence, although less complete, suggests the probability that rates are also high.

Studies of the dramatic emergence of diabetes and its manifestations in these aboriginal groups has considerable potential for gaining a better understanding of the genetic and environmental factors which influence risk and pathophysiology of diabetes and its complications.
Diabetogenic Effect of Streptozotocin in the Rat During the Perinatal Period
Authors: Portha B , Levacher C , Picon L , Rosselin G
Published: December 2014

The diabetogenic effect of streptozotocin was investigated in the rat during the fetal and neonatal life. Streptozotocin was directly injected in the vitellin vein of the fetus or in the saphenous vein of the neonate. In the 21.5 day old fetus, diabetogenic activity was demonstrated with a single dose of 100 μg/gm. administered the day before, and this was indicated by a fall in the pancreatic insulin content to 20 per cent and a lowering of the plasma insulin to 60 per cent of the controls. A single dose (100 μg/gm.) of streptozotocin administered on the day of birth produced an overt diabetes in the neonate: the maximal fall in the pancreatic insulin content (7 per cent of the controls) was observed four days after the streptozotocin injection, during the highest blood glucose level (300 per cent of the controls). A significant increase in the pancreatic glucagon content was observed twenty-four hours after the maximal insulin depletion. Liver glycogen content was occasionally decreased. More severe diabetes was obtained by two streptozotocin injections (50μg/gm.), with lowest pancreatic and highest blood glucose levels at 1 per cent and 60 per cent, respectively. A clearcut drop of the plasma insulin/glucose ratio was observed in the drug-treated animals. Three weeks after injection(s), basal blood glucose and plasma insulin levels were normal, although impairment of insulin secretion still appeared after glucose load and insulin pancreatic content was still slightly lower. A rapid and spontaneous, if not quite complete recovery, is a characteristic pattern of the streptozotocin diabetes in the neonate as compared to that in the adult.
Increased “Glucagon Immunoreactivity” in Plasma of Totally Depancreatized Dogs
Authors: Vranic Mladen , Pek Sumer , Kawamori Ryuzo
Published: December 2014

Elevated plasma glucagon immunoreactivity (IRG) observed in overt diabetes and during prolonged fasting is assumed to be the result of increased secretion of pancreatic glucagon. In seven healthy mongrel dogs diabetes was induced by total pancreateetomy During the first two weeks following surgery, porcine NPH (6 to 12 U, once daily) and Regular insulin (6 to 12 U twice daily) were administered. Thereafter, insulin treatment was discontinued and the dogs were fasted for periods up to seven days. Plasma IRG was measured using antiglucagon serum G9-I which is 95 per cent specific for pancreatic glucagon. Fifteen hours after the last insulin injection an intraportal infusion of Regular insulin was given in amounts sufficient to achieve normoglycemia: mean IRG (pg./ml.) was 118 ± 34, a value similar to that observed in the fasting intact animals (134 ± 33). After insulin withdrawal, as fasting continued, plasma IRG increased progressively in all dogs. On Days 5 and 6-7, after insulin withdrawal, when peripheral plasma insulin was undetectable and marked hyperglycemia, hyperlipacidemia and ketonuria prevailed, mean IRG was 624 ± 136 and 986 ±184, respectively. The highest level of IRG observed was 1450 in one dog on Day 7. These results are confirmed by using three other antiglucagon sera considered to be specific for pancreatic glucagon. We conclude that: 1) Progressively increasing amounts of material crossreacting with “specific” antiglucagon sera appear in plasma of totally depancreatized dogs fasting for up to seven days. 2) This event appears to be the consequence of metabolic derangements induced by insulin lack. 3) Hyperglucagonemia can result onoly from a defect of the pancreatic α cell, but can also be the consequence of excessive production of IRG from a nonpancreatic source. It could be that glucagon deficiency cannot be easily demmonstrated, because the release of nonpancreatic IRG can compensate for lack of pancreatic glucagon.
Insulin Potentiating Action of a Peptide Fraction from Human Urine
Authors: Ng Frank M , Zimmet Paul Z , Seiler Gwen , Taft Pincus , Bornstein Joseph
Published: December 2014

An impure peptide preparation from human urine has been shown to have similar biological effects in vitro and in vivo to synthetic peptides containing the human growth hormone sequence Leu-Ser-Arg- Leu-Phe-Asp- Asn-Ala (residues 6–13). The urinary preparation potentiates the action of insulin in the isolated rat diaphragm and in rabbits and rats, but the latter animals are far more sensitive to its action. Species specificity is possibly a significant factor in determining dosage in future studies.
Insulin Degradation: VI. Feedback Control by Insulin of Liver Glutathione-Insulin Transhydrogenase in Rat
Authors: Varandani P T , Nafz Mary Ann , Shroyer Lois A
Published: December 2014

The changes in the hepatic levels of glutathione-insulin transhydrogenase (GIT) in response to changes in the blood levels of insulin in rats under a variety of conditions have been determined by quantitative specific immunochemical titrations using antiserum to purified rat liver GIT. The GIT concentration was consistently lower in decreased insulin states brought about by starvation and by alloxan diabetes than in normally fed rats. Subsequent refeeding of starved rats with standard laboratory chow restored the loss in GIT content. Treatment of alloxandiabetic rats with insulin for two days increased concentration of GIT greatly above normal; administration of the A chain or B chain of insulin in the same manner was ineffective and did not augment or inhibit the effect of insulin. The insulin-mediated increase of GIT in diabetic rats was nullified by concomitant administration of either actinomycin D (an inhibitor of RNA synthesis) or cycloheximide (an inhibitor of protein synthesis). Thus, the data indicate that insulin induces synthesis of GIT protein via RNA synthesis. The biological significance of the induction of the GIT protein by insulin is interpreted as a feedback mechanism to regulate the insulin levels in the body. The results provide further evidence that GIT activity is the primary determinant of the rate of hepatic insulin metabolism. It must be assumed, however, that other factors are also involved in the regulatory process of insulin degradation, and some possibilities are suggested.
Mechanisms Involved in the Exercise-induced Increase in Glucagon Secretion in Rats
Authors: Luyckx Alfred S , Lefebvre Pierre J
Published: December 2014

Previous studies in our laboratory indicate that a marked rise in plasma pancreatic glucagon occurs in rats subjected to non-exhausting exercise (forced swim or FOSWI). Male albino rats fas led overnight Were subjected to FOSWI for thirty to sixty minutes in tepid water. Blood for glucose, free fatty acids, insulin and glucagon determinations was obtained by cardiac puncture immediately after exercise or after a rest period in control animals. The FOSWI-induced rise in plasma glucagon was of pancreatic origin since it was significant with an antiserum highly specific for pancreatic glucagon and an antiserum weakly cross-reacting with gut GLI but absent with a nonspecific antiserum. Theglucagon rise was even more important in hypophysectomized rats. Intraperitoneal glucose injection (0.2 gnu per kilogram) decreased plasma glucagon in resting animals but did not abolish FOSWI-induced glucagon secretion. Adrenalectomy slightly reduced the glucagon response to FOSWI, whereas propranolol pretreatment (5 mg per kilogram intraperitoneally) completely blocked the glucagon rise. Phentolamme (25 mg. per kilogram) increased blood glucose, plasma IRI and glucagon in resting animals. FOSWI did not further increase the already elevated glucagon levels in the phentolamine-treated rats. The exercise-induced glucagon rise persisted in rats pretreated with phentolamine (5 mg. per kilogram) and practolol (12.5 mg. per kilogram). It is concluded that catecholamines and, in particular, sympathetic innervation of the islets play a major role in the exercise-induced glucagon secretion ana tfiat the adrenergic receptors involved are likely of the β2 type.
Glucose Metabolism and Insulin Secretion in the Newborn Infant: Comparisons Between the Responses Observed the First and Seventh Day of Life to Intravenous and Oral Glucose Tolerance Tests
Authors: Falorni A , Fracassini F , Massi-Benedetti F , Maffei S
Published: December 2014

Insulin secretion and glucose metabolism were studied during intravenous and oral glucose tolerance tests performed in one day and seven day old full-term and premature infants. Mean glucose disposal during the intravenous tests was more rapid in seven day old than in one day old infants.

Insulin responses after intravenous glucose were characterized by higher insulin levels during the initial phase and lower levels during the second phase in both seven day old premature and full-term groups as compared with the patterns seen in one day old infants. No differences in the mean values for blood glucose and plasma insulin were found among the four groups of infants at any time during the oral tests.
Glycogen Accumulation in Retinal Neurons and Glial Cells of Streptozotocin-diabetic Rats: Quantitative Electron Microscopy
Authors: Sosula Leo , Beaumont Paul , Hollows Frederick C , Jonson Keith M , Regtop Hubert L
Published: December 2014

The concentration of glycogen β-particles was measured in the inner retinal layers of normal and streptozotocin-diabetic rats with quantitative electron microscopic technics. Diabetes was uncontrolled and of short duration (thirty days). Blood glucose levels in the normal and diabetic animals were 76 ± 8 S.E. and 340 ± 25 S.E. mg./100 ml. Diabetes caused glycogen accumulation in the amacrine, bipolar, ganglionic, Müller and capillary mural cells. Quantitative estimates showed significant increases (p < 0.001) in the glycogen concentrations of cells in the nerve fiber layer (NFL), inner plexiform layer (IPL) and inner nuclear layer (INL) of the diabetic retinas.

The glycogen concentrations increased from 6.4 ± 0.41 β-particles per square micron in the normal to 10.5 ± 0.85 in the diabetic Müller endfeet (NFL); from 12.9 ± 1.5 to 38.6 ± 5.0 in the Müller processes (IPL); from 0.81 ± 0.13 to 3.37 ± 0.49 in the neural processes (IPL); from 2.7 ± 0.66 to 17.3 ± 2.4 in the amacrine cell bodies (INL). Diabetic glycogen accumulation occurred at a greater rate in the neurons than in the Müller cells. The amacrine neurons were the most severely affected and contained massive glycogen deposits in their cytoplasm.

The glycogen concentration in the neurons was less than that of the Müller cells. However, the Müller cells represent only ∼10 per cent of the total cytoplasm of the IPL, whereas the neurons occupy ∼90 per cent of this layer. From the above data, it is evident that the neurons contain about one third of the total glycogen of the normal IPL. In the diabetic IPL, the total glycogen is approximately evenly distributed between the neural and glial compartments.
Sodium Retention Accompanying Insulin Treatment of Diabetes Mellitus
Authors: Saudek Christopher D , Boulter Philip R , Knopp Robert H , Arky Ronald A
Published: December 2014

Urinary sodium excretion before and during insulin therapy was studied in six patients with poorly controlled diabetes. One subject had ketoacidosis; manifestations in the other five ranged from slight ketoacidosis to hyperglycemia alone. All patients retained sodium when diabetes was controlled by insulin, the mean positive sodium balance being 286 mEq. over three days. The diminished urinary sodium excretion did not correlate with the fall in glucosuria or ketonuria; insulin withdrawal studies in two patients indicated that sodium depletion during insulin lack is not a prerequisite for sodium retention during retreatment Im-munoreactive glucagon fell from elevated levels as control of diabetes was established.

It is concluded that sodium retention occurs regularly during insulin treatment of poorly controlled diabetes, whether ketoacidosis is present or not. The positive sodium balance should be anticipated when insulin therapy is instituted.
Sexual Dysfunction in Diabetic Men
Authors: Kolodny Robert C , Kahn Charles B , Goldstein H Howard , Barnett Donald M
Published: December 2014

Sexual function was studied in 175 diabetic male outpatients randomly selected. Data collected included medical and sexual histories, physical examination, complete blood count, urinalysis, T4, 12 channel chemistry screening profile and plasma testosterone determination. Eighty-five of the 175 men were impotent (49 per cent), four reported premature ejaculation (2 per cent) and two subjects had retrograde ejaculation (1 per cent). In the group with impotence, the mean age of the subjects and duration of diabetes were respectively fifty-three and six years. In patients without impotence, the comparable values were fortyfive and five years.

Typically, the onset of impotence was gradual, usually progressing over a period of six months to a year with an interval during which firmness of erection was decreased. Levels of sexual interest were sustained in almost all subjects. Over 90 per cent of the males studied gave a pattern of impotence compatible with an organic rather than a psychologic etiology.

Occurrence of impotence'was not definitely correlated with duration of diabetes or with insulin or oral agents. Incidence of peripheral neuropathy was increased in the group with sexual dysfunction.

Plasma testosterone levels were within normal limits in impotent diabetics or in the group without impotence, respectively (mean ± S.E.M.) 627 ±15 and 637 ± 14 ng per cent. It is apparent from these findings that androgen deficiency was not an etiologic factor in this group of diabetic men with impotence.
Diabetic Neuropathic Cachexia
Authors: Ellenberg Max
Published: December 2014

Six patients with diabetic neuropathy are reported who conform to a hitherto undescribed syndrome. The two outstanding symptoms, namely profound weight loss and severe pain, led to the admitting diagnosis of metastatic carcinoma or carcinomatous neuropathy in each case. The patients were all males, chiefly in the sixth decade of life, had bilateral symmetrical peripheral neuropathy, severe emotional disturbances, anorexia, impotence, mild diabetes, simultaneous onset of neuropathy and diabetes, absence of other specific diabetic complications and a uniformly spontaneous recovery in about one year. Because of the cachectic appearance, the term ‘diabetic neuropathic cachexia’ is suggested.
Clinical Studies of Alcoholic Ketoacidosis
Authors: Cooperman Michael T , Davidoff Frank , Spark Richard , Pallotta Johanna
Published: December 2014

Seven episodes of severe ketoacidosis in six nondiabetic patients were recognized at this hospital within an eighteen month period. All were women; one pregnant patient experienced two episodes at twenty-eight and thirty-two weeks' gestation. All patients admitted to heavy chronic alcohol intake and drinking binges.

On admission, these patients were conscious and alert. Mean values were 143 mg./100 ml. for plasma glucose and 7.25 for arterial pH. Plasma bicarbonate was depressed with a mean anion gap of 18. Beta-hydroxybutyrate/acetoacetate ratio averaged 5.2. All patients had liver function abnormalities. Mean serum immunoreactive insulin was low, 5μU./ml. (n=2), while cortisol was markedly elevated at 76.5μg. per cent (n=3); mean growth hormone level was 14.1 ng./ml. (n=3). Free fatty acid concentration, measured on admission in one episode, was 1,945 mEq./L. Therapy with glucose, saline, and minimal amounts of alkali led to prompt recovery. Circulating levels of cortisol, insulin and growth hormone were measured serially in one patient during recovery; they quickly returned to normal.

The dissociation of severe ketosis from glycosuria and hyperglycemia in these patients raises important questions concerning coupling of ketogenesis to gluconeogenesis. The striking preponderance of women, including one pregnant patient, reported with this condition also suggests a possible role for ovarian and placental hormones in its pathogenesis; fetal drain on carbohydrate reserves may further contribute to the tendency to ketosis.

Alcoholic ketoacidosis may be relatively common, since we saw one case of this syndrome for about every four of diabetic ketoacidosis during this period.
Insulin and Glucose Responses to Identical Oral Glucose Tolerance Tests Performed Forty-eight Hours Apart
Authors: Olefsky Jerrold M , Reaven Gerald M
Published: December 2014

We compared the plasma glucose and insulin responses to two identical oral glucose tolerance tests performed forty-eight hours apart in thirty-one adult patients. The mean results of the two tests were essentially identical, indicating that no consistent difference in glucose or insulin response occurs upon repetitive oral glucose tolerance testing. When the variability of the glucose response curves were analyzed by comparing repeat values to each other, it was found that nine of thirty-one fasting values deviated by more than 10 per cent, but no fasting values deviated by more than 30 per cent. The one hour value was more variable: Twenty-two of thirty-one observations deviated by more than 10 per cent and six of thirty-one deviated by more than 30 per cent. The variability of the insulin response was greater. For example, fourteen of thirtyone fasting values deviated by more than 10 per cent, and three of thirty-one deviated by more than 30 per cent, while twenty-six of thirty-one one hour values deviated by more than 10 per cent and twenty-one of thirty-one deviated by more than 30 per cent. Furthermore, the ratio of the insulin response to the glucose response (I/G ratio) was as variable as was the insulin response alone. The extreme variability of the insulin response to identical glucose loads, coupled with similar variability of the I/G ratio, suggests that factors other than glucose concentration play a role in regulating insulin response.
Purification and Immunologic Identification of Aldose Reductases
Authors: Gabbay Kenneth H , Cathcart Edgar S
Published: December 2014

A general method for the identification and purification of aldose reductase (alditohNADP oxidoreductase, EC 1.1.1.21) and NADP-L-hexonate dehydrogenase (L-gulonate:NADP oxidoreductase, EC 1.1.1.19) from tissues is described. Two aldose reductase isoenzymes, AR-A and AR-B, were isolated from renal papilla and were characterized. These two forms were also found in brain, retina, pancreas, lens and optic nerve. AR-A and AR-B differed primarily in glucuronate-reducing activity. All tissues, with the exception of lens and optic nerve, also contained NADP-L-hexonate dehydrogenase activity. Human red blood cells contained NADP-L-hexonate dehydrogenase activity but not aldose reductase.

The aldose reductases and the two isoenzyme forms isolated from these tissues were immunologically identical as demonstrated with a specific antiserum prepared in rabbits against papillary AR-B. The antiserum inhibited AR-A and AR-B activity equally in vitro. The extent of enzyme inhibition by the antiserum was similar when glucuronate, glucuronolactone, xylose and glyceraldehyde were used as substrates. The antiserum did not react with NADP-L-hexonate dehydrogenase. Therefore, the method provides a specific means for identifying aldose reductase in crude tissue homogenates.
Acute Metabolic Effects of Human Growth Hormone
Authors: Fineberg S Edwin , Merimee Thomas J
Published: December 2014

These studies were done to clarify the actions of human growth hormone (HGH) during the two hours after concentrations were increased. These effects cannot be attributed to generation of somatomedin. Mean systemic levels of HGH were increased to 92.6 ng. per milliliter by the intravenous infusion of 4 mg. of HGH over thirty minutes. During the first hour, mean plasma glucose and free fatty acid (FFA) concentrations decreased by 9.5 ± 1.9 per cent and 21.2 ± 3.6 per cent, respectively. After two hours, FFA concentrations rose to 145 per cent of basal.

An identical preparation of HGH was then perfused across forearm tissues at mean forearm venous concentrations of 28.4 ± 1.5 ng. per milliliter or 200.3 ± 7.9 ng. per milliliter. Glucose uptake was acutely decreased (by 30 per cent) by both doses of HGH; neither dose had significant effects upon lipolysis. Therefore, neither physiologic nor supraphysiologic concentrations of HGH had an insulin-like effect upon peripheral muscle or adipose tissue. Small increases in peripheral HGH concentrations had virtually identical effects upon enhancement of potassium uptake and reduction of glucose uptake across muscle as mean concentrations ten times higher.
Studies of Glucagon Secretion in Pancreatectomized Patients
Authors: Muller W A , Brennan M F , Tan M H , Aoki T T
Published: December 2014

Intravenous arginine infusions were performed in two totally pancreatectomized patients and two age/sex-matched normal subjects. Plasma glucagon concentrations did not increase in the pancreatectomized patients, whereas a four- to sixfold rise of the glucagon levels following arginine administration was seen in the control subjects. Measurements of plasma glucagon-like im-munoreactivity revealed no difference between normal and pancreatectomized subjects. The data suggest the absence of a significant number of normally functioning alpha cells in extrapancreatic sites.
Cerebral Edema and Depression of Sensorium in Nonketotic Hyperosmolar Coma
Authors: Arieff Allen I , Carroll Hugh J
Published: December 2014

The influence of body water and solute equilibria between extracellular fluid and cerebrospinal fluid (CSF), both before and during therapy, was studied in fifty-three patients who had hyper-glycemia (blood glucose 600 mg./100 ml.) in the absence of ketoacidosis. Particular attention was directed to both depression of sensorium and the possible production of cerebral edema. Before therapy, depression of sensorium was highly correlated with plasma osmolality (r =.84), but not with glucose concentration or pH of either CSF or plasma. Plasma and CSF were in osmotic equilibrium before therapy (389 mOsm/kg.) but glucose concentration was significantly higher in plasma while Na+ and Cl− were higher in CSF. During treatment with insulin and hypotonic NaCl infusion, the osmolalities of CSF and plasma fell at essentially identical rates. Plasma osmolality fell as a consequence of both a fall in glucose concentration and a gain in free water, but the fall in CSF osmolality was almost entirely due to a gain in water by the CSF. Insulin administration was stopped when plasma glucose was about 250 mg./100 ml., and in all patients there was no increase in CSF pressure or clinical evidence of cerebral edema.

In patients with nonketotic coma, depression of sensorium is highly correlated with the plasma osmolality. During therapy with insulin and hypotonic NaCl infusion, it appears that cerebral edema does not occur if insulin is stopped before plasma glucose falls below 250 mg./100 ml.
Altered Glucoregulatory Hormones During Acute Pneumococcal Sepsis in the Rhesus Monkey
Authors: George David T , Rayfield Elliot J , Wannemacher Robert W
Published: December 2014

To determine the effects of a Diplococcus pneumoniae infection upon the dynamics of glucose metabolism and the hormones responsible for its control, intravenous glucose tolerance tests (IVGTT's) were performed in monkeys during baseline control conditions and twenty-four hours after initiating infection when the monkeys were febrile. Along with plasma glucose, immunoreactive insulin and glucagon concentrations were measured sequentially through each IVGTT. Furthermore, fasting concentrations of plasma amino acids, immunoreactive growth hormone and cortisol were determined.

These data reveal no differences in the fasting plasma concentrations of growth hormone and glucose, or in the disappearance rates of glucose during the two IVGTT's. There was, however, a mild relative hyperinsulinemia (p < 0.05) (following glucose) along with fasting hyperglucagonemia (p < 0.01) during infection. Of the twenty-one amino acids measured, twenty were depressed during infection; only cysteine was elevated (p < 0.05) in the infected monkeys. Although plasma cortisol levels were significantly (p < 0.05) increased above preinfection values by the stress of infection, they remained within the control range.

The hyperglucagonemia and depression of the mean insulin: glucagon molaf ratio are compatible with the catabolic events occurring during a mild bacterial infection in the monkey.
Are Abnormalities in Insulin Secretion Responsible for Reactive Hypoglycemia?
Authors: Hofeldt Fred D , Lufkin Edward G , Hagler Louis , Block Marshall B , Dippé Stephen E , Davis John W , Levin Seymour R , Forsham Peter H , Herman Robert H
Published: December 2014

Seventy patients with reactive hypoglycemia strictly defined by criteria which interpret the low blood glucose value in relationship to clinical and physiologic parameters, were studied to determine if abnormalities in insulin secretion could be demonstrated. These patients were separated into four groups: alimentary (N = 5), diabetic (N = 16), hormonal (N = 5), and idiopathic (N = 44). The findings in these patients were compared to normal control subjects and to weight- and disease-matched patient controls. All of the patients with hormonal and most patients with idiopathic reactive hypoglycemia (thirty-two of forty-four) demonstrated delayed insulin secretion regardless of the control group used for comparison. Diabetic reactive hypoglycemic patients exhibited delayed insulin secretion when compared to normal controls but not when compared to weight-matched diabetic controls. Excessive insulin secretion was consistently found only in the patients with the alimentary variety of reactive hypoglycemia. Using weight- and diseasematched control groups, no abnormalities in insulin secretion could be found to account for the hypoglycemia in the diabetic reactive hypoglycemic patients and some idiopathic reactive hypoglycemic (nine of forty-four) patients. These results help to explain the inconsistent findings of previous investigators and suggest that reactive hypoglycemia is a syndrome having multiple etiologies.
Effect of Phenformin on Glucose-Insulin Interrelationships
Authors: Stout R W , Brunzell J D , Bierman E L , Porte D
Published: December 2014

Phenformin was administered to nine male subjects with fasting plasma glucose levels below 110 mg./lOO ml. and oral glucose tolerance levels ranging from clearly normal to mildly abnormal. Most of the subjects were slightly overweight, but weight was maintained constant throughout the study. Two weeks' administration of phenformin, 100 mg. per day, resulted in a fall in fasting plasma glucose levels both on a 45 per cent carbohydrate (mean change −4 per cent) and an 85 per cent carbohydrate diet (mean change −2 per cent). The glucose-lowering effect of the drug was not related to the initial glucose level, and the glucose-lowering effect of increased dietary carbohydrate was not altered by the drug. Both the total and the incremental glucose responses to oral glucose tended to be reduced by phenformin. Intravenous glucose tolerance (Kg) was improved by the drug, the mean change being similar to the mean change in oral glucose tolerance (−12 per cent). Basal insulin levels on both diets were lowered by phenformin (mean change −23 per cent) as were the total insulin responses to both oral and intravenous glucose (mean changes −18 per cent and −19 per cent respectively). It is suggested that phenformin's primary action is to enhance peripheral glucose assimilation, and that the changes in insulin secretion are secondary to this, having a counter-regulatory role in preventing profound hypoglycemia, and minimizing the changes in blood glucose in nondiabetic subjects. The absence of any drug effect on the acute insulin response to intravenous glucose (per cent basal) is consistent with the depressed insulin secretion being secondary to the drug's effect on glucose metabolism, rather than to a direct effect of phenformin on the pancreatic islets. The similar changes in the effect of the drug on oral and intravenous glucose tolerance suggest that impairment of intestinal glucose absorption is not an important effect of phenformin.
Characterization of Carbohydrate Metabolism in the Isolated Fetal Rat Heart: Effects of Fasting and Alloxan Diabetes
Authors: Vinicor Frank , Kohalmi Diane , Clark Charles M
Published: December 2014

Studies have been made on the effects of maternal fasting and alloxan-induced diabetes on fetal and maternal plasma glucose and insulin concentrations, as well as on fetal myocardial and hepatic glycogen concentrations. Maternal fasting for sixteen hours, ending seventy-two hours prior to sacrifice, had no effect on maternal glucose and insulin concentrations. Under these conditions fetal insulin and hepatic and myocardial glycogen concentrations were also unchanged; fetal plasma glucose increased [from 16±2 to 26±3 mg.'100 ml. (p<0.02]. A sixteen-hour maternal fast immediately preceding sacrifice significantly decreased maternal insulin and glucose concentrations. Fetal hepatic and myocardial glycogen levels and insulin concentrations were also decreased; fetal glucose again increased [from 35±1 to 43±1 mg.'100 ml. the fetal rat, and the importance of fetal insulin on fetal glycogen concentrations are discussed.

Maternal alloxan diabetes produced elevated glucose concentrations, unchanged insulin values, decreased hepatic glycogen and increased myocardial glycogen in the fetuses. Possible mechanisms for these findings are discussed. Fetal myocardial glucose uptake in vitro was not affected by either fasting or maternal diabetes.

The data suggest that, whereas near-term fetal rats do possess some ability to control their glucose and glycogen concentrations, manipulation of maternal nutrition by fasting or alloxan diabetes can significantly alter fetal carbohydrate metabolism.