bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Chronic Oral Antidiabetic Therapy on Insulin and Glucagon Responses to a Meal
Authors: Tsalikian Eva , Dunphy Thomas W , Bohannon Nancy V , Lorenzi Mara , Gerich John E , Forsham Peter H , Kane John P , Karam John H 
Published: September 2013

Nineteen maturity-onset diabetic patients receiving oral hypoglycemic therapy in a university diabetes dinic completed a study to assess the efficacy of the oral agents and to determine their effects on pancreatic islet hormone secretion. All patients were receiving sulfonylureas, and seven were also receiving phenformin. Hie subjects were studied as outpatients in the clinic setting on four different occasions with collections of a baseline blood sample before a standard breakfast and a second sampling two hours postprandially, twice while on their prescribed medication and twice after having been withdrawn from the medication. The values obtained during the two studies on and the two studies off medications were reproducible for each subject. Analysis of the results by paired differences revealed that mean 24-hour urine glucose values deteriorated significantly (p &lt; 0.005) after oral antidiabetic therapy was withdrawn; similarly, mean plasma glucose values, both at baseline and two hours postprandially, rose significantly (p &lt; 0.001) when subjects were off medication. Baseline serum insulin values were not changed, but postprandial levels were significantly higher on oral agents (p &lt;0.005). Plasma immunoreactive glucagon was significantly lower both at baseline (p &lt; 0.02) and postprandially (p &lt; 0.005) when the subjects were on their antidiabetic medications. During the trial off medication, 16 patients became symptomatic, with three of these developing symptoms severe enough to require hospitalization.
It is apparent from this study that oral hypoglycemic medications can play a role in controlling symptoms in maturity-onset diabetic patients and that the beneficial effect of these agents on hyperglycemia may, in part, be explained by their stimulation of endogenous insulin secretion and partial suppression of endogenous glucagon.
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.
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.
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 &lt; 0.005), but there was no consistent relationship of the insulin-binding capacity to the degree of diabetic instability (r = 0.15, p &gt; 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.
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.
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).
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.
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.
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&lt;0.02). Patients with IMCP were found to inject less insulin daily, and six of them were adequately treated with only one daily injection.
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.