bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucagon Response to Arginine Stimulation in Obese and Diabetic Children
Authors: Meschi Franco , Garlaschi Cristina , Natale Berardo Di , Guercio Maria José Del , Gargantini Luigi , Chiumello Giuseppe
Published: September 2013

The effect of arginine infusion on blood sugar and plasma levels of growth hormone and glucagon has been studied in children with clinical diabetes mellitus and in obese children with normal carbohydrate tolerance. Basal levels of plasma GH are significantly lower in obese children than in diabetics and controls; in obese subjects the increment of GH is significantly lower than in diabetics and controls. Basal plasma glucagon levels are comparable in all three groups despite the high sugar levels in diabetic patients. After arginine infusion there is a significant rise in glucagon levels without significant differences between the three groups.
The Effects of Long-term Therapy with Oral Hypoglycemic Agents on the Oral Glucose Tolerance Test Dynamics in Male Chemical Diabetics
Authors: Tan M H , Graham C A , Bradley R F , Gleason R E , Soeldner J S
Published: September 2013

The effect of fixed doses of oral hypoglycemic agents and placebo (diet alone) on the blood glucose, serum insulin, triglyceride, and cholesterol responses during oral glucose tolerance tests done annually for up to four years' follow-up was studied, in a doubleblind manner, in five groups of mild male chemical diabetics. The drugs used were chlorpropamide (100 mg. O.D.), tolbutamide (500 ing. b.i.d.), phenformin (50 mg. O.D.), acetohexamide (250 mg. O.D.), and placebo. Each subject was given an individualized diet aimed at attaining and maintaining ideal weight.

Comparison by chi-square analysis between the placebo group and each of the drug groups showed (a) no significant differences with regard to the number of subjects with normal glucose tolerance in each of the tests and (b) no change in the insulin secretion dynamics. Comparison between the initial test and each of the subsequent tests within each group showed (a) a greater number of subjects with normal glucose tolerance in the first follow-up test in the chlorpropamide group only, (b) no change in the insulin secretion dynamics except in the chlorpropamide group, where there was an increased insulin/glucose ratio in the first follow-up test, and (c) no change in the fasting serum triglyceride and cholesterol levels.
Control of Hyperglycemia in Adult Diabetics by Pulsed Insulin Delivery
Authors: Genuth Saul , Martin Paul
Published: September 2013

Nine adult diabetic subjects were treated for two weeks by an intravenous insulin-delivery system that provided preprogramed five-hour pulses of insulin with each meal such that a normal diurnal pattern of plasma insulin was attained. Plasma insulin peaked at 800 per cent of basal and at approximately 45 minutes after the onset of each pulse. On day 14, mean plasma glucose (hourly sampling × 22) was 94 mg./100 ml., with a range of 66 to 125 mg./100 ml. Eighty-eight per cent of all values were between 50 and 150 mg./100 ml. The dose of insulin required correlated significantly with the degree of obesity. On the first posttreatment day, hourly plasma glucose remained significantly below pretreatment levels while the endogenous plasma insulin area increased 46 per cent above pretreatment values (p < 0.01). Six of the patients still exhibited slight improvement in glucose tolerance for seven days while on diet but not on insulin treatment. It is concluded that insulin replacement, coordinated with meals in a physiologic manner, can virtually normalize plasma glucose even without feedback control of delivery rates. Definite but transient remission of beta-cell dysfunction may follow.
Short-term Effect of Insulin and 5(3-Piridyl) Tetrazole on Serum Triglycerides in Insulin-dependent Diabetic Patients
Authors: Alvarez-Reynolds M , Dominguez J M
Published: September 2013

A group of insulin-dependent diabetic patients was studied in order to determine the possible short-term regulatory effect of insulin and that of an antilipolytic drug on serum triglycerides.

Subcutaneous crystalline insulin (one third of the usual morning dose of intermediate long-acting insulin, NPH) and an oral dose of 5(3-piridyl) tetrazole, 800 mg., were administered.

During the three-hour period of the study, the amount of both substances was sufficient to suppress free fatty acids and to produce a progressive lowering of serum triglycerides without significant changes in serum cholesterol. However, although the level of blood sugar was normalized with insulin, it did not change with the administration of 5(3-piridyl) tetrazole. The rate of fall of plasma free fatty acids and serum triglycerides was similar in both substances and positively correlated with its basal concentration.
Diabetic Vascular Changes in Children
Authors: Malone John I , Cader Thomas C Van , Edwards William C
Published: September 2013

The microvascular complications of diabetes are demonstrated in the eye at a very early stage with the use of retinal ftuorescein angiography. One hundred and fifty-four children who have had diabetes mellitus for durations varying from one month to 18 years had their retinal vasculature evaluated with fluorescein angiography. Seventy-five per cent of the children examined had vascular abnormalities, including 20 children who had diabetes for one year or less. Twenty-five per cent of the children showed no vascular abnormalities. This included one child who had diabetes for 12 years. The severity of the vascular abnormalities increased with the duration of diabetes. Vascular abnormalities did not appear related to diabetic management or control. The possibility of two types of diabetes, one with and the other without associated vascular abnormalities, is suggested.
Peripheral Nerve Fiber Size in Experimental Diabetes
Authors: Sharma A K , Thomas P K , Molina A F De
Published: September 2013

Serial morphometric observations were made on the tibial nerves of mature rats before and five weeks after the induction of diabetes by streptozotocin. Maximum and average myelinated Fiber diameter did not alter, neither did the relationship between myelin sheath thickness and axon circumference. This confirms previous observations suggesting that the reduced nerve conduction velocity that is known to occur in experimental diabetes is likely to depend on metabolic alterations rather than on structural changes.
Studies on the Etiology of “Brittle Diabetes”: Relationship Between Diabetic Instability and Insulinogenic Reserve
Authors: Shima Kenji , Tanaka Ryoichi , Morishita Suzue , Tarui Seiichiro , Kumahara Yuichi , Nishikawa Mitsuo
Published: September 2013

To clarify possible etiologie mechanisms for brittleness of diabetic control, a relationship between the degree of diabetic instability and insulinogenic reserve or insulin-binding capacity of plasma IgG was studied in 46 insulin-treated diabetics attending the outpatient clinic. Evaluation of insulinogenic reserve was based on elevations of plasma C-peptide immunoreactivity (CPR) during the oral glucose tolerance test (OGTT). The degree of instability was quantified by the standard deviations (S.D.) of 10 values of fasting blood glucose, which were determined for the last six months while subjects were attending a hospital as outpatients. An inverse correlation was evident between residual B-cell secretory capacity and blood glucose regulatory instability (r = −0.69, p < 0.005), but there was no consistent relationship of the insulin-binding capacity to the degree of diabetic instability (r = 0.15, p > 0.05). Furthermore, pancreatic A-cell functions were investigated in seven unstable and seven stable diabetics, classified according to their S.D. values. Although immunoreactive glucagon (IRG) responses to an infusion of arginine were observed, plasma IRG did not rise in unstable diabetics during insulin-induced hypoglycemia, in which condition IRG in stable diabetics rose significantly. In contrast, plasma cortisol responses to the insulin-induced hypoglycemia were demonstrated in both diabetic groups. Plasma CPR did not decrease in unstable but did in stable diabetics fol towing the insulin injection. The comparison of unstable diabetic patients with more stable ones on the basis of clinical data, such as means of age, duration of diabetes mellitus, duration of insulin therapy, and dose of insulin, revealed no significant difference.

The total lack of insulinogenic reserve results inevitably in loss of the automatic regulation of circulating insulin levels, which seems to be one of the essential factors for causing the hyperla-biUty of diabetic control. The pancreatic A-cell dysfunction is also attributable in part to the metabolic variability in brittle diabetes.
The Effect of Somatostatin on Glucose Uptake and Production by Rat Tissues in Vitro
Authors: Cherrington A D , Caldwell M D , Dietz M R , Exton J H , Crofford O B
Published: September 2013

Somatostatin has recently been used as a tool to investigate the roles of insulin and glucagon in the regulation of glucose metabolism in vivo. The alterations in glucose uptake and production that somatostatin causes have been attributed to the modifications it induces in pancreatic hormone levels rather than to effects of the peptide per se, although the direct effects of the latter on glucose turnover have not been clearly assessed. The aim of the present study therefore was to determine whether or not somatostatin directly affects either the rate of glucose uptake by fat and muscle or the rate of glucose production by the liver.

Glucose uptake by the perfused rat hindquarter (skeletal muscle) was unaltered by somatostatin (10-1,000 ng./ml.) whether or not the process was stimulated by insulin (250 μU./ml.). Basal and insulin-(5-40 / μU./ml.)-stimulated glucose oxidation (uptake) by isolated rat adipocytes was also unaffected by somatostatin (5-500 ng./ml.). In addition, the peptide had no effect on basal or glucagon-(10−l0–10−9 M)-stimulated glucose output by isolated rat liver cells. Somatostatin also failed to modify the actions of these sub-maximally effective levels of glucagon on either the intracellular level of cAMP or the activity of cAMP-dependent protein kinase. The present studies support the hypothesis that the acute changes in the level and turnover of glucose induced by somatostatin are attributable to its effect on the endocrine system rather than to its direct effects on glucose metabolism.
Effects of Dietary Composition on Adipose Tissue Hexokinase-II and Glucose Utilization in Normal and Streptozotocin-diabetic Rats
Authors: Bernstein Robert S , Marshall Merville C , Carney Alice L
Published: September 2013

The control of adipose tissue hexokinase isoenzymes in response to altered dietary composition was investigated. Rats that were fasted and then refed carbohydrate-free diets increased their HK-II activity in epididymal fat pads above the level in fasted animals. However the ultimate activity of HK-II achieved during refeeding with seven diets of varying composition was dependent mainly on dietary carbohydrate; the effect of dietary carbohydrate overcame poor growth due to protein deficiency or decreased food intake. Fat pads from animals fed for three weeks from weaning with 19 per cent protein diets showed a marked increase in HK-II on 51 per cent carbohydrate over those on a carbohydrate-free diet but no further increase on 81 per cent carbohydrate. However, adipocytes from rats on 81 per cent carbohydrate had significantly higher HK-II than those from rats on 51 per cent carbohydrate.

In streptozotocin-diabetic rats there was no difference in adipose tissue HK-II between rats on 19 per cent protein-51 per cent carbohydrate and those on 19 per cent protein carbohydrate-free diets. Treatment of diabetic rats with 3 U. lente insulin daily brought HK-II into the range for normal rats, but once again there was no difference between the two diets. The treated rats showed marked weight gain but were still hyperglycemie.

Adipocytes from rats on the 19 per cent protein carbohydrate-free diet showed lower HK-II and glucose conversion to CO2 and triglyceride than adipocytes from rats on the 51 per cent carbohydrate diet. There was a high correlation of HK-II to both pathways of glucose utilization on both diets. However, the slope of the regression line of triglyceride production on HK-II was much lower on the carbohydrate-free than on the basal diet. Adipocytes from rats on the 81 per cent carbohydrate diet had HK-II activity and glucose utilization that fell within the 95 per cent confidence limits for the relationship derived from adipocytes from rats on the 51 per cent carbohydrate diet. Values for glucose utilization in adipocytes from treated diabetic rats on the carbohydrate-free diet were above the expected range for this diet for both CO2 and triglyceride production; CO2 production was also above the expected range for diet in treated diabetic rats on the 51 per cent carbohydrate diet. Glucose conversion to both end products was higher for a given level of HK-II in the treated diabetic animals on the 51 per cent carbohydrate diet than on the carbohydrate-free diet.

These data indicate that diet has a major effect on HK-II that is probably mediated by carbohydrate and is dependent on insulin. Although there appears to be a relationship between HK-H and glucose utilization in a given diet-and-treatment group, there is a departure from the normal relationship in adipocytes from rats on a high-fat carbohydrate-free diet or from partially treated diabetic rats.
Serum Glucose Levels and Alcohol-consumption Habits in a Large Population
Authors: Gérard Marie José , Klatsky Arthur L , Siegelaub Abraham B , Friedman Gary D , Feldman Robert
Published: September 2013

Using information from approximately 100,000 multiphasic check-ups performed in these facilities, we have found an association between alcohol-drinking habits and serum glucose values one hour after an oral challenge with 75 gm. of glucose. There was a positive dose-response relation between reported alcohol intake and serum glucose level over the most common range of alcohol intake. Serum glucose levels were highest in the group who consumed six to eight alcoholic drinks per day. However, among those who said they took nine or more drinks per day, mean serum glucose levels were significantly lower than in the six-to-eight-drink group. These relations persisted when the analysis was controlled for the effects of age, sex, race, adiposity, time since last food intake, time of day, previously known diabetes, and previously known liver disease. A search of the literature failed to uncover a complete explanation for these phenomena.
Growth Hormone Antiserum Suppresses the Growth Effect of Diabetic Serum: Studies on Rabbit Aortic Medial Cell Cultures
Authors: Ledet Thomas
Published: September 2013

Growth medium containing serum from young diabetic subjects caused a significant stimulation both of cell proliferation and of the outgrowth in cultures of rabbit aortic medial cells above that noted with normal human sera. The addition to the sera of guinea-pig human growth hormone antibody caused a marked inhibition of these stimulatory effects. The growth effect of rabbit serum was not affected by the human growth hormone antiserum.

Reinvestigation of the effect of human growth hormone disclosed that the same increase as observed in growth with the diabetic sera could be obtained with a growth hormone concentration of 0.2 ng. per milHliter medium.

The present results strongly suggest that the increased stimulatory effect of normolipemic human diabetic serum on growth and cell proliferation of aortic medial cell cultures is due to increased serum growth hormone concentration.
Effects of Hypocalcemia and Theophylline on Glucose Tolerance and Insulin Release in Human Beings
Authors: Gedik O , Zileli M S
Published: September 2013

A study was carried out to investigate the role of serum calcium in the regulation of insulin secretion and glucose tolerance in response to an oral glucose load on human subjects in hypocalcemie and normocalcemic states. The subjects for this study comprised three groups. Group 1 consisted of 15 patients with hypoparathy-roidism. They were subjected to an oral glucose load, and blood samples were taken at 0, 30, 60, 90, 120, 150, and 180 minutes to determine the blood glucose and serum insulin levels. These patients were treated with vitamin D2; after normocalcemic states were achieved the same study was repeated. This group of patients showed an abnormal glucose tolerance test and a markedly reduced insulin release during their hypocalcemie state; these abnormalities returned to normal after treatment. Group 2 consisted of six patients with hypoparathyroidism and one patient with vitamin-D-resistant rickets. These patients were subjected to an oral glucose load and a theophylline infusion (1 gm. in three hours) when they were hypocalcemie. The theophylline infusion increased the insulin release to the level of control subjects' in spite of hypocalcemia. Ten healthy volunteers served as a control group (group 3).

Our results indicate that serum calcium has an important role in glucose utilization by insulin release.

This is the first experiment to be performed on human beings and shows that theophylline has a stimulatory effect on insulin secretion in the presence of hypocalcemia.
Metabolic Effects of the Glucose Tolerance Factor (GTF) in Normal and Genetically Diabetic Mice
Authors: Tuman Robert W , Doisy Richard J
Published: September 2013

The acute metabolic effects of glucose tolerance factor (GTF), the biologically active form of trivalent chromium, were studied in normal and genetically diabetic (db/db) mice. A single intraperitoneal injection of GTF significantly reduced the nonfasting plasma glucose level in normal mice by 38 per cent, and in diabetic mice by 14 to 29 per cent. Time course studies in normal and diabetic mice showed a maximal lowering of plasma glucose at four hours after GTF treatment. Furthermore, a single injection of GTF significantly lowered the elevated plasma triglyceride and cholesterol levels by 47 and 35 per cent, respectively, four hours after injection. Genetically diabetic mice are refractory to insulin, and treatment with exogenous insulin produced a smaller decrement in plasma glucose (11-18 per cent). The combination treatment of diabetic mice with GTF and exogenous insulin was significantly more effective in reducing plasma glucose (39-51 per cent) and triglycerides (76 per cent) than either treatment alone. These findings are consistent with the suggestion that GTF and insulin act synergjstically.
Unexplained Hyperinsulinemia in Normal and “Prediabetic” Pima Indians Compared with Normal Caucasians: An Example of Racial Differences in Insulin Secretion
Authors: Aronoff Stephen L , Bennett Peter H , Gorden Phillip , Rushforth Norman , Miller Max
Published: September 2013

The pattern of insulin response to oral and/or intravenous glucose has been claimed to be characteristic of diabetes and even prediabetes. To determine if differences in insulin secretion might explain the exceptionally high prevalence of diabetes in the Pima Indians, 26 genetically normal Pimas (nondiabetic offspring of nondiabetic parents), 32 genetically prediabetic Pimas (nondiabetic offspring of diabetic parents), 10 diabetic Pimas, and 29 normal Caucasians were studied. All subjects received an intravenous glucose tolerance test (IVGTT) to examine the acute-phase insulin response, and all nondiabetic subjects received an oral glucose tolerance test (OGTT) and arginine infusion (AI). The prediabetics also received a cortisone-primed oral glucose tolerance test (CGTT) and were classified by the result of this test.

While acute-phase insulin release during the IVGTT was absent in the diabetics, there was a rapid response in all nondiabetics. Prediabetic Pimas with normal or abnormal CGTT had insulin levels similar to normal Indians during the IVGTT, OGTT, and AI. Thus, no evidence of impairment of acute- or late-phase insulin release was found. The normal and prediabetic Indians had fasting and stimulated insulin levels during all the tests two-to-threefold greater than the Caucasians. Differences in insulin levels between the two races could not be explained by differences in glucose level, age, or obesity.
HLA Antigens in Diabetic Children
Authors: Illeni Maria Teresa , Pellegris Giuseppe , Guercio Maria José Del , Tarantino Antonio , Busetto Fernanda , Pietro Carmelo Di , Clerici Enrico , Garotta Gianni , Chiumello Giuseppe
Published: September 2013

Ninety insulin-dependent diabetic children were HLA-typed in order to elucidate the role played by HLA complex-linked genes in the pathogenesis of diabetes melHtus of childhood. HLA-Aw30 and HLA-Bw35 were significantly increased and decreased, respectively, in the diabetic group as compared with controls. In relation to age at onset of diabetes, HLA-B8 was significantly increased in the 0-5-year group.

By dividing the patients according to the season at onset of the disease, only HLA-Aw30 in the October-January group reached the level of significance (P=0.05).
The Prader-Willi Syndrome Regulation of Fat Transport
Authors: Bier D M , Kaplan S L , Havel R J
Published: September 2013

Studies of fat mobilization and transport are reported in six patients with the Prader-Willi syndrome. Two patients had carbohydrate intolerance. One of these had a low and the other an augmented insulin response to glucose challenge. Following challenge with glucose, three of the four nondiabetics had normal insulin responses or increased responses consistent with their obesity; the other nondiabetic had insulinopenia. Measurements of the effects of norepinephrine, insulin, glucose, and 5-methylpyrazole-3-carboxylic acid on plasma levels of FFA, glycerol, and ketones provide no evidence for abnormal regulation of mobilization of fat from adipose tissue. Measurements of plasma lipids and postheparin lipolytic activity are consistent with normal uptake of fat into adipose tissue, and normal fatty acid composition of adipose tissue gives no evidence for abnormal Upogenesis.
Diabetic Glomerulopathy Following Unilateral Nephrectomy in the Rat
Authors: Steffes Michael W , Brown David M , Michael Mauer S
Published: September 2013

One month following induction of diabetes with streptozotocin, one half of diabetic and control rats underwent unilateral nephrectomy. Subsequently, all animals were studied with respect to renal function and glomerular alterations of diabetes. Blood pressure levels were similar in all animals. Diabetic and control animals with unilateral nephrectomy had similar but elevated serum creatinine levels and lower creatinine clearance values as compared with the intact rats. However, on a per kidney basis the creatinine clearance levels were higher in the animals with unilateral nephrectomy. At both three and six months following nephrectomy, markedly increased mesangial matrix thickening and mesangial deposition of IgG and C3 were observed in diabetic rats with unilateral nephrectomy as compared with intact diabetic animals. Nephrectomy had no detectable effects on glomerular morphology or im-munohistochemistry of nondiabetic rats. Thus, unilateral nephrectomy in the rat increases, at as early as three months, the severity of diabetic glomerular lesions.
Hyperglycemia, Hypoinsulinemia, and Hyperglucagonemia in Acute Water Intoxication
Authors: Thurston Jean Holowach , Hauhart Richard E , Dirgo John A
Published: September 2013

When acute (four-hour) hyponatremia with clinical signs of water intoxication was produced in normal weanling mice by the use of hypotonie glucose or deionized water, there was a two-to-fourfold increase in plasma glucose concentration. Concomitantly, concentrations of plasma insulin fell 63 to 68 per cent, whereas plasma glue agon increased to 262 per cent of control. The findings are compatible with stress-induced catecholamine release.
Characterization of Seven C-peptide Antisera
Authors: Faber O K , Binder C , Markussen J , Heding L G , Naithani V K , Kuzuya H , Blix P , Horwitz D L , Rubenstein A H
Published: September 2013

The plasma C-peptide immunoreactivity (CPR) in 10 normal subjects varied considerably when measured with different antisera in parallel assays. The CPR level correlated with the blank “CPR” value measured in plasma devoid of C-peptide and to a lesser degree with the sensitivity of the standard curves obtained with the individual antisera.

Storage of plasma samples at different temperatures and for different lengths of time before the analyses were carried out resulted In further variation in the CPR results. This was caused by a time- and temperature-dependent fall in CPR, which was more pronounced with some antisera than with others. This sensitivity to storage of plasma did not correlate with the antigenk characteristics of the antisera as determined by their reactivity with 11 specific fragments of the C-peptide molecule.

The contribution of human proinsulin to the CPR concentration in normal subjects was considered to be negligible even though the relative immunoreactivity of human proinsulin and C-peptide ranged from 11 to 143 per cent among these antisera.

These results suggest that differences in C-peptide antisera are a major reason for the variation in the concentration of circulating CPR as measured in different, C-peptide immunoassays.
C-peptide Metabolism and the Liver
Authors: Kühl C , Faber O K , Hornnes P , Jensen S Lindkaer
Published: September 2013

It is generally assumed that C-peptide is not degraded in the liver to any significant extent. This assumption is, however, based on indirect evidence. We therefore measured the hepatic extraction ratio (R) of insulin and C-peptide in anesthetized pigs with simultaneous sampling of portal and hepatic venous blood. Blood samples were taken at one-minute intervals for 10 minutes during basal (unstimulated) experimental conditions as well as after intravenous injection of 1 mg. glucagon into four normal-weight and four obese pigs. The hepatic extraction ratio of insulin or C-peptide was calculated as the portal concentration minus the hepatic concentration divided by the portal concentration. The average pre- and poststimulatory molar ratios of C-peptide to insulin were 1.5 ± 0.11 (S.E.M.) and 1.2 ± 0.06 in portal blood and 3.4 ± 0.21 and 2.2 ± 0.08 in hepatic blood. For all pigs the mean Rc-peptide was 0.30 ± 0.03 and 0.33 ± 0.02 pre- and poststimulatory, respectively. The corresponding figures for Rinsulin (0.71 ± 0.02 and 0.61 ± 0.02) were both significantly higher (p < 0.01). The mean R-values for C-peptide and insulin were consistently higher in obese pigs than in normal-weight pigs (p < 0.01). Additional experiments in two normal-weight pigs showed that ligation of the hepatic artery elicited a significant fall of mean Rc-peptide, which, however, never became less than 0.12. These results suggest that besides the wellknown hepatic extraction of insulin, the livers of anesthetized pigs also extract significant amounts of endogenous C-peptide. Hepatic extraction of C-peptide is, however, about 50 per cent lower than that of insulin.
Kinetics of Human C-peptide in Man
Authors: Faber Ole K , Kehlet Henrik , Madsbad Sten , Binder Christian
Published: September 2013

A review of studies concerned with the metabolism of human C-peptide showed that the kidney is the major organ in C-peptide removal. The turnover rate of C-peptide was similar to that of proinsulin but considerably slower than that of insulin.

An analysis of corresponding C-peptide and insulin concentrations in normal subjects after the administration of oral glucose or intravenous glucagon was used to define the relationships between the two peptides. These results show that different peripheral vein concentrations of insulin may correspond to identical C-peptide concentrations, depending on sampling conditions.
Residual Beta-cell Function and Its Metabolic Consequences
Authors: Binder Christian , Faber Ole K
Published: September 2013

Improvement in the sensitivity and specificity of the C-peptide immunoassay and studies of larger groups of patients have increased our knowledge of the importance of residual beta-cell function and its metabolic consequences in insulin-treated diabetic patients. During the first five to 10 years after the onset of diabetes mellitus residual beta-cell function is demonstrable in the majority of insulin-treated patients irrespective of the severity of the initial symptoms and only partly dependent on the patient's age at diagnosis. Residual beta-cell function facilitates good control. Stable patients have a higher C-peptide concentration in plasma than unstable ones, but unmeasurable C-peptide is not always associated with poor control. More data are needed before the full significance of an even minimal reserve of beta-cell function is elucidated. It also remains to be shown whether the reduction in beta-cell function in diabetic patients has a qualitative as well as quantitative component.
Insulin Therapy in Relation to Circulating C-peptide Levels
Authors: Beischer W , Kerner W , Raptis S , Keller L , Beischer B , Pfeiffer E F
Published: September 2013

Part 1. Beta-cell secretion was stimulated maximally by an intravenous glibenclamide-glucose load in four groups of 10 adultonset diabetics divided according to their therapy, which was determined by clinical criteria. Under the standardized conditions of this test, the 20 patients requiring insulin had a mean fasting blood glucose (BG) of 255 mg./100 ml. and showed no stimulation of immunoassayable C-peptide (IMCP) by glibenclamide-glucose. In contrast, the mean fasting BG was 160 mg./100 ml., but the IMCP rose in patients who were able to be managed with sulfonylurea tablets. These differences in IMCP proved to be of value for the clinician in predicting the efficacy of diabetes therapy with either insulin or sulfonylurea tablets.

Part 2. Twenty-four-hour profiles of BG and IMCP were per performed in 28 insulin-requiring diabetics (age range: 14 to 74 years) who were 66 to 111 per cent of normal weight and had had diabetes for 0.2 to 31 years. These patients were divided into diabetics with IMCP (n = 14) and without IMCP (n = 14); the mean age and weight were similar in the two groups. The mean IMCP value and its standard deviation correlated inversely with the mean blood glucose (MBG) in all diabetics and healthy subjects. According to clinical criteria, diabetes control was better in the patients with IMCP. Analysis of variance showed that the mean BG concentrations for diabetics with and without IMCP were statistically different (p<0.02). Patients with IMCP were found to inject less insulin daily, and six of them were adequately treated with only one daily injection.
Prevalence of Residual Beta-cell Function in Insulin-Dependent Diabetics in Relation to Age at Onset and Duration of Diabetes
Authors: Madsbad S , Faber O K , Binder C , McNair P , Christiansen C , Transbøl I
Published: September 2013

The influence of the age at onset as well as the duration of disease on the prevalence of residual beta-cell function was studied in insulin-dependent diabetic patients. Two hundred and sixty-seven patients presented at an early age (10–19.9 years) and 158 patients had a late onset (30–39.9 years of age). Beta-cell function was evaluated by measuring serum C-peptide immunoreactivity. Fifty-six patients (21.0 per cent) in the early-onset group and 64 (40.5 per cent) in the late-onset group had residual beta-cell function. The prevalence of residual beta-cell function was almost 100 per cent during the first two years of disease and was lower thereafter in diabetics with early onset. About 15 per cent of all patients with a duration between 15 and 35 years had residual beta-cell secretory function.
Somatostatin in Maturity-onset Diabetes
Authors: Christensen S E , Hansen Aa P , Lundbæk K
Published: September 2013

Plasma FFA, glucagon, insulin, glucose, and growth, hormone were followed every hour during 24 hours of saline infusion, 24 hours of somatostatin (4 mg.) infusion, and three hours without infusion in six nonobese and six obese maturity-onset diabetic men.

Somatostatin induced the same changes in the parameters of both groups of diabetic patients: A rise in plasma FFA, which gradually disappeared after some hours of infusion, a suppression of plasma glucagon and insulin, and an augmentation of plasma glucose both postprandially and during the night. Plasma growth hormone was suppressed in the nonobese patients, but somatostatin could not further suppress the low and nonfluctuating plasma growth hormone concentration in the obese maturity-onset diabetics.

The results indicate that a preparation with a pattern of hormone suppression like that of somatostatin will not be useful in the control of maturity-onset diabetes, because it suppresses insulin and elevates the blood glucose concentration.
Syngeneic Transplantation of Fetal Rat Pancreas: II. Effect of Insulin Treatment on the Growth and Differentiation of Pancreatic Implants Fifteen Days After Transplantation
Authors: McEvoy Robert C , Hegre Orion D
Published: September 2013

Eight 18-days-postcoltum fetal pancreases were transplanted to isogenic alloxan-diabetic male rats. Some recipients were treated with insulin for seven days immediately after transplantation. Eight animals in both the insulin-treated group and control group were killed 15 days after transplantation for morphologic and hormonal studies of the transplanted tissue. Using the morphometric technique of linear scanning, the insulin, glucagon, and somatostatin immunocytochemically positive, cell masses of the fetal pancreatic implants were quantitated.

The beta cell mass of the implants from the control animals increased roughly eightfold from the time of transplant; insulin treatment resulted in a further two- to threefold increase. The insulin content of the implants increased more than did the beta cell mass, resulting in the fivefold increase in insulin per beta cell. The alpha cell and delta cell masses did not change during the transplant site, the mass of functional beta cells, and the cell-to-cell content of the implanted tissue.

These results are discussed in relation to previous quantitative studies of pancreatic islet cell growth. The relationships of the transplant site, the mass of functional beta cells, and the cell-to-cell interaction within the islet to the maintenance of glucose homeostasis are also discussed.
Cholesterol Metabolism in Diabetes: I. The Effect of Diabetic Control on Sterol Balance
Authors: Saudek Christopher D , Brach Elizabeth L
Published: September 2013

To evaluate the effect of diabetic control on sterol balance, five subjects (one with fasting chylomicronemia) were studied when they had little control of blood glucose (period I) and, continuously, when increased insulin dosage improved diabetic control (period II). The four subjects with no chylomicronemia showed a diminished fecal bile acid (FBA) excretion. Although fecal neutral steroid excretion increased variably, the total steroid balance was unchanged. The results support the concept that good control of diabetes shifts the fecal steroid excretion towards diminished FBA, but steroid balance methods did not reveal an effect of insulin on total steroid balance.
Glucose and Amino Acid Metabolism in Perfused Skeletal Muscle: Effect of Dichloroacetate
Authors: Goodman Michael N , Ruderman Neil B , Aoki Thomas T
Published: September 2013

Dichloroacetate lowers blood glucose and diminishes blood levels of lactate, pyruvate, and alanine in both starvation and diabetes. To determine the role of skeletal muscle in these changes, studies were carried out in intact rats, with the isolated perfused rat hindquarter and soleus muscle preparation. In hindquarters from fed, starved, and diabetic rats, dichloroacetate alone or in the presence of insulin did not augment glucose uptake. On the other hand, it dramatically curtailed the release of the gluconeogenic precursors lactate, pyruvate, and alanine. Dichloroacetate increased markedly the generation of 14CO2 from lactate-1-14C in starved and diabetic rats, suggesting activation of pyruvate dehydrogenase. The increment in lactate oxidation was stoichiometri-cally equivalent to the decrease in lactate plus alanine release. Glycolysis, as determined from the sum of lactate and alanine release plus lactate oxidation in the hindquarter and from the formation of 3H2O from 3-3H-glucose by the incubated soleus muscle, was not altered by dichloroacetate. Dichloroacetate curtailed the release of most amino acids in the perfused hindquarter of fed rats. In starved and diabetic rats, it caused an increase in the release of valine, leucine, and isoleucine, suggesting inhibition of their metabolism. As judged from lactate-pyruvate and 3-hydroxybutyrate-acetoacetate ratios and changes in tissue α-glycerol-phosphate, perfusion with dichloroacetate caused the cytosol of the muscle cell to become more reduced and the mitochondria more oxidized. Similar changes occurred when it was administered to intact animals. These findings suggest that the hypoglycemic effect of dichloroacetate is, at least in part, due to a decrease in the release of gluconeogenic precursors from skeletal muscle secondary to activation of pyruvate dehydrogenase.
Antibody Binding of Insulin in Diabetic Ketoacidosis
Authors: Scott R S , Espiner E A , Donald R A , Smith J R
Published: September 2013

This study investigates the effects of insulin antibody binding on free insulin levels measured in patients with acute diabetic ketoacidosis receiving insulin by constant infusion. In spite of antibody binding ranging from 10 to 90 per cent of the total circulating insulin, the steady state concentrations of free insulin were similar to those observed in individuals on identical infusion rates but without insulin-binding antibodies. However, the levels of free insulin in two patients were substantially lower than expected for the rate of insulin infusion, even though levels of bound insulin were not greatly elevated. An infusion rate of at least 4 U. per hour produced satisfactory rate of fall of plasma glucose, whereas lower dose regimens (2 U. per hour)—producing steady state free insulin concentrations ranging from 28 to 49 mU. per liter in different subjects—were unreliable in controlling the metabolic abnormalities of diabetic ketoacidosis.
The Pathogenic Role of an Insulin-receptor Defect in Diabetes Mellitus of the Obese
Authors: Beck-Nielsen Henning
Published: September 2013

I-125-insulin binding to circulating monocytes was measured in 12 obese, maturity-onset diabetic patients, in 10 obese subjects, and in 12 normal persons. The diabetic obese patients were extremely insulin resistant and had an impaired glucose tolerance, while the normoglycemic obese subjects were slightly insulin resistant and had borderline values of glucose tolerance. The insulin secretion pattern of diabetic obese patients after a glucose load differed from that of the normal and normoglycemic obese subjects, showing a low initial response.

Insulin binding to monocytes from diabetic obese patients showed a 40 per cent decrease when compared with normal persons (p <0.05). Furthermore, insulin binding to monocytes was about 20 per cent lower in diabetic obese than in normoglycemic obese subjects. However, this difference was not statistically significant (p >0.1). In the total group of persons studied, the insulin binding correlated positively to both glucose tolerance (R = 0.69, p <0.001) and insulin sensitivity (R = 0.74, p <0.001). In the separate groups we also found a statistically significant correlation between insulin binding and insulin sensitivity in normoglycemic obese (R = 0.69, p <0.05) but not in diabetic obese subjects (R = 0.36, p > 0.1)

After 10 days of treatment with a 1200-kcal. diet the diabetic patients exhibited significant increases in glucose tolerance (p < 0.01), in insulin sensitivity (p < 0.01), and in insulin binding (p < 0.01)

We conclude that a close correlation exists between insulin binding and insulin sensitivity in the three groups studied. Among obese subjects the correlation was less pronounced (statistically insignificant) in diabetic obese persons, emphasizing that, especially in this group, there are other factors of importance for the insulin resistance in addition to the receptor defect.
Aspirin Stimulates Insulin and Glucagon Secretion and Increases Glucose Tolerance in Normal and Diabetic Subjects
Authors: Micossi Piero , Pontiroli Antonio E , Baron Steven H , Tamayo Raul C , Lengel Frieda , Bevilacqua Maurizio , Raggi Umberto , Norbiato Guido , Foà Piero P
Published: September 2013

Normal subjects and patients with adult-onset diabetes received 10 gm. of aspirin in four days. On the fourth day, the fasting serum glucose and the glucose response to oral glucose were decreased in both groups. These changes were associated with increased levels of serum insulin and pancreatic glucagon, although the glucagon responses to oral glucose were unchanged. In the diabetic patients, aspirin therapy was followed by a decreased glucose response to I.V. glucose and by the appearance of an early insulin peak, which could not be demonstrated before treatment. Aspirin did not affect the I.V. glucose tolerance in normal subjects, although it did enhance the early insulin peak. A decrease in the fasting levels of free fatty acids was noted in both groups, whereas the fasting level of triglycerides decreased only in the diabetic patients. Cholesterolemia did not change in either group. A few preliminary observations indicate that, in normal subjects, ibuprofen and ketoprofen, two other presumed prostaglandin inhibitors, did not affect fasting glycemia, glucose tolerance, or the insulin response to glucose. No changes were noted after the administration of placebo.
Carbohydrate Diet-induced Changes in Very Low Density Lipoprotein Composition and Structure
Authors: Witztum Joseph L , Schonfeld Gustav
Published: September 2013

High carbohydrate (CHO) diets cause accumulation in plasma of larger, triglyceride (TG)-enriched very low density lipoprotein (VLDL) particles. In man, the composition of the VLDL is changed by such diets as well. The source of the altered VLDL particles is presumed to be the liver, but the intestine is known to secrete VLDL, and VLDL is also altered during its postsecretory catabolism. To ascertain that the liver is a source of “diet-induced VLDL,” we fed rats CHO and control diets and we examined plasma levels of lipids chemically and apoproteins A-I (ApoA-I) and B (ApoB) by specific radioimmunoassay (RIA). VLDL (d < 1.006) and VLDL density subfractions were isolated and their composition studied by RIA, column chromatography, isoelectric focusing (IEF), and polyacrylamide gel electrophoresis. Livers from control and CHO-fed rats were perfused in vitro. Whole perfusates and perfusate VLDL were studied similarly.

In the CHO-fed rats, plasma TG increased, cholesterol and ApoA-I remained unchanged, and ApoB fell. The VLDL isolated were TG enriched and less dense. Although total VLDL-protein rose, the proportion of VLDL-protein that was ApoB and arginine-rich protein (ARP) fell, while ApoC rose. The ApoB content varied directly with density of particles. ARP subunits were not changed, but relative proportions of ApoC-III0 rose from 39 to 46 per cent of dye uptake on IEF gels and ApoC-III3 fell from 34 to 26 per cent. Thus, CHO feeding produced altered plasma VLDL in the rat.

The perfused livers of the CHO-fed rat secreted more TG, but absolute secretory rates for cholesterol, ApoB, and ApoA-I were unchanged. The VLDL isolated from perfusates were larger, TG-enriched, and less dense. Although VLDL-protein rose, the proportion that was ApoB fell; both ApoC and ARP rose, ARP sub-units were unchanged, while ApoC-III0 rose from 29 to 37 per cent and ApoC-III3 fell from 48 to 42 per cent. In contrast to plasma, ApoC content was not increased relative to ARP. As in plasma, content of ApoB varied with particle density.

Thus, CHO feeding induced changes in hepatic perfusate VLDL structure and composition that in general paralleled those changes seen in plasma. This strongly suggests that the action of diet on the liver is responsible for many of the changes seen in plasma VLDL. On the other hand, the discrepancy between the VLDL-ApoC content and subunit proportions of plasma and perfusate suggests that the discrepancy is due to postsecretory processing. Similarly, the failure to see decreases in absolute hepatic ApoB secretion, while plasma ApoB levels fell, suggests that the postsecretory metabolism of ApoB-containing lipoproteins is also altered by diet. In addition, the failure to see increases in hepatic VLDL-ApoB secretory rates at a time when VLDL-TG and VLDL-protein increased suggests that there is no tight coupling between the secretion of ApoB and lipids.
Quantitative Vitreous Fluorophotometry: A Sensitive Technique for Measuring Early Breakdown of the Blood-retinal Barrier in Young Diabetic Patients
Authors: Waltman Stephen R , Oestrich Charles , Krupin Theodore , Hanish Sidney , Ratzan Susan , Santiago Julio , Kilo Charles
Published: September 2013

Vitreous and aqueous humor fluorescein concentrations were measured one hour after graded intravenous fluorescein was given to 20 juvenile diabetics, ages 20 to 40, with and without ret-inopathy, and to 12 controls of similar age. Vitreous fluorescein concentrations were significantly higher in diabetics, indicating breakdown of the blood-retinal barrier. Mean vitreous fluorescein values were 10.66 ± 0.65 for the diabetics and 4.28 ± 0.37 ng./ml. for the controls. Breakdown of the blood-retinal barrier was also confirmed in diabetics under the age of 20 without retinopathy. The blood-aqueous barrier was similarly altered in diabetics. Vitreous fluorophotometry quantitatively measures breakdown of the blood-retinal barrier, possibly the earliest detectable ocular vascular abnormality in juvenile diabetic patients.
Circulating Alanine Production and Disposal in Healthy Subjects
Authors: Chochinov R H , Perlman K , Moorhouse J A
Published: September 2013

Circulating-alanine production and disposal rates were estimated in eight healthy postabsorptive subjects by means of U-14C alanine and U-14C glucose infusions. The mean circulating-alanine production rate was 368 ± S.E.M. 28 μmol/min. · 1.82. Approximately 50 per cent of circulating-alanine carbon exchanged rapidly with that of circulating lactate. Approximately 30 per cent of circulating alanine exchanged with protein stores. Other disposal was 29 ± 2 per cent to circulating glucose and 40 ± 4 per cent to oxidation. Conclusions: (1) The carbon moieties of circulating alanine and lactate are freely exchangeable. (2) Assessment of the contribution of alanine to gluconeogenesls will depend on establishing the extent to which the precursor pyruvate carbon is derived from glycolysis or from proteolysis. (3) If the principal pyruvate precursor is glycolysis, then the principal specific function of the glucose-alanine cycle appears to be ammonia transport.
Nasal Absorption of Insulin in Dogs
Authors: Hirai Shinichiro , Ikenaga Toshiaki , Matsuzawa Tai
Published: September 2013

The Intranasal application of an Insulin solution in dogs resulted in the rise of plasma immunoreactive insulin and in dose-dependent hypoglycemie. The absorption of insulin from this site was found to be enhanced when insulin was dissolved in an acid medium. In addition, when an insulin preparation with some surfactant was used, the effectiveness of nasally administered insulin was 25 to 30 per cent of that achieved with intravenously administered insulin.