bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beneficial Effect of Chromium-rich Yeast on Glucose Tolerance and Blood Lipids in Elderly Subjects
Authors: Offenbacher Esther G , Pi-Sunyer F Xavier 
Published: September 2013

SUMMARY
Twenty-four volunteers, mean age 78, including eight mildly non-insulin-dependent diabetics, were randomly allocated to one of two groups and were fed (daily for 8 wk) 9 g of either chromium-rich brewers' yeast (experimental) or chromium-poor torula yeast (control). Before and after yeast supplementation, the serum glucose and insulin response to 100 g oral glucose was measured at 30 min intervals for 2 h. Fasting serum cholesterol, total lipids, and triglycerides were also determined. In the total experimental group (normals + diabetics) and in both the diabetic and nondiabetic experimental subgroups, glucose tolerance improved significantly and insulin output decreased after supplementation. Cholesterol and total lipids fell significantly after supplementation in the total experimental group. The cholesterol decrease was particularly marked in hypercholesterolemic subjects (cholesterol &gt; 300 mg/dl). In the control group, no significant change in glucose tolerance, insulin, triglycerides, or total lipids was found. Cholesterol was significantly lowered in the nondiabetic but not in the diabetic group. Thus, chromium-rich brewers' yeast improved glucose tolerance and total lipids in elderly subjects, while chromium-poor torula yeast did not. An improvement in insulin sensitivity also occurred with brewers' yeast supplementation. This supports the thesis that elderly people may have a low level of chromium and that an effective source for chromjum repletion, such as brewers' yeast, may improve their carbohydrate tolerance and total lipids. The improvement in serum cholesterol in some control subjects, as well as in the total experimental group, also suggests the presence of a hypocholesterolemic factor other than chromium in both brewers' and torula yeast.
Ventromedial Hypothalamic Lesions Increase Pancreatic Sensitivity to Streptozotocin in Rats
Authors: West David B , Seino Yutaka , Woods Stephen C , Porte Daniel 
Published: September 2013

SUMMARY
Rats with electrolytic lesions of the ventromedial hypothalamus (VMX rats) and sham-operated controls (SHAM rats) were injected with streptozotocin (STZ) at a dose of 50 mg/kg 48 h after the lesions were made. VMX rats were significantly more sensitive to STZ in that over 70% died within 6 wk, whereas none of the SHAM rats died. When smaller doses of STZ were given to VMX rats (30–35 mg/kg), a large percentage still died, although the survivors appeared equally as diabetic (in terms of hyperglycemia and hypoinsulinemia) as SHAM rats given a larger dose of STZ. At 25 mg/kg, the surviving VMX rats were more hyperglycemic than matched controls. We suggest that the increased B-cell activity known to occur in VMX animals might be the important factor in the increased sensitivity to STZ observed. We speculate that similar variation in pancreatic B-cell response to an environmental injury may be an important determinant of diabetes susceptibility in man.
Type I (Insulin-dependent) Diabetic Multiplex Families: Mode of Genetic Transmission
Authors: Walker Angela , Cudworth A G 
Published: September 2013

HLA genotypes have been analyzed in 120 classic type I (insulin-dependent) diabetic sib pairs with an age of onset below 16 yr reported to the British Diabetic Association register (1972–78). By this age, siblings of diabetic children are 26 times more likely to develop type I diabetes than other children. There is a highly significant disturbance in the zygotic assortment of HLA haplotypes in these sib pairs, providing conclusive evidence for the existence of major susceptibility genes in the HLA complex.
The present data exclude a simple dominant or recessive mode of inheritance. It is likely that both parents contribute to the susceptibility, indicating the presence of two HLA-linked genes (or clusters of genes in linkage disequilibrium) that influence the predisposition to the disease. There is no evidence that type I diabetic multiplex families have an increased HLA risk or increased predisposition to autoimmunity compared with families with one affected child.
Arterial Procollagen Type I, Type III, and Fibronectin: Effects of Diabetic Serum, Glucose, Insulin, Ketone, and Growth Hormone Studied on Rabbit Aortic Myomedial Cell Cultures
Authors: Ledet Thomas , Vuust Jens 
Published: September 2013

Arterial myomedial cell cultures were grown from thoracic aortas of normal rabbits. The effect of normolipemic serum from young nonobese male juvenile diabetics on the production of procollagen type I, type III, and fibronectin was studied on nearly confluent primary cultures not treated with trypsin and incubated in the presence of [U-14C]-proline. The macromolecules were isolated from the incubation medium by ammonium sulfate precipitation, fractioned by DEAEcellulose chromatography and SDS urea-polyacrylamide gel electrophoresis, and quantitated by liquid scintillation counting.
Media containing diabetic serum enhanced the production of procollagen type I (P &lt; 0.05). There was no effect on the elaboration of procollagen type III. Diabetic serum, however, stimulated the production of fibronectin (P &lt; 0.005). There was no relationship between the glucose level and the amount of either procollagen type I or fibronectin.
Growth medium supplemented with normal serum and extra glucose did not change the production of procollagen type III or fibronectin but decreased the elaboration of procollagen type I (P &lt; 0.05). Addition of insulin (100 μU/ml) resulted in a significant decrease in procollagen type I, type III, and fibronectin elaboration (P &lt; 0.05, P &lt; 0.02). When ketones (0.2 mM) were added together with normal serum, no changes in the procollagens and fibronectin were observed.
Supplementation of normal serum with human growth hormone (1 ng/ml) resulted in a significant increase in the production of procollagen type I (P &lt; 0.02) and fibronectin (P &lt; 0.01).
The present results demonstrate that the factor(s) in normolipemic diabetic human serum enhancing theproduction of procollagen type I and fibronectin by arterial myomedial cell cultures cannot be imputed to glucose, insulin, or ketones, but leaves growth hormone as one possible factor
The data may be relevant for the understanding of the development of human diabetic macroangiopathy.
Amino Acid Transport in Isolated Hepatocytes from Streptozotocin-diabetic Rats
Authors: Samson Michel , Fehlmann Max , Dolais-Kitabgi Jacqueline , Freychet Pierre 
Published: September 2013

The enhanced ability of liver to extract glucogenic precursors from plasma in insulinopenic diabetes was investigated at the cellular level by measuring amino acid transport in isolated hepatocytes from streptozotocin-diabetic rats. The concentrative Na+-dependent uptake of α-amino[1-14C]isobutyric acid (AIB), a nonmetabolizable analog of alanine, was increased in hepatocytes from diabetic rats compared with controls. This increase was observed both at a low (0.1 mM) and high (30 mM) extracellular concentration of the amino acid. Analysis of the relationship between AIB influx and AIB concentration revealed that the increased uptake in diabetic rat hepatocytes was due to an enhanced capacity (i.e., a twofold increase in the Vmax) of the transport system whereas the apparent affinity (Km) for AIB was unaltered.
The increased amino acid transport activity in diabetic rat hepatocytes was due mainly to an increased transport through system A (alanine-preferring) and, to a much lesser extent, through system ASC (alanine, serine, cysteine). System L (leucine-preferring) and AIB entry through simple diffusion were not affected in diabetic rat hepatocytes compared with controls. Increased AIB transport of diabetic rat hepatocytes was returned to normal by insulin treatment.
Direct Evidence for Downregulation of Insulin Receptors by Physiologic Hyperinsulinemia in Man
Authors: Soman Vijay R , DeFronzo Ralph A 
Published: September 2013

To directly examine whether physiologic hyperinsulinemia regulates insulin receptors in normal man, we studied the effect of insulin infusion (employing the euglycemic insulin clamp technique) on 125I-insulin binding to monocytes. In Study I (9 subjects), when the steady-state plasma insulin concentration was raised to approximately 100 μU/ml, insulin binding to monocytes remained unchanged at 1 h, but decreased significantly by 3 h (20%, P &lt; 0.01) and fell further by 5 h (37%, P &lt; 0.001) following the insulin infusion. In Study II (5 subjects) increments in plasma insulin concentration to 31 μU/ml resulted in no change in insulin binding at 3 h (P &gt; 0.5) but resulted in a significant decrease at 5 h (25%, P &lt; 0.01). The plasma glucose concentration was maintained at basal levels in both infusion protocols. The decrease in insulin binding in both studies was due to a decrease in insulin receptor concentration. No significant change in receptor affinity was observed. In a control study (5 subjects) 5 h of saline infusion had no effect on insulin binding to monocytes.
We conclude that in normal humans, increments in the plasma insulin concentration in the physiologic range downregulates the number of insulin receptors in a dose- and time-dependent manner.
Insulin Resistance in Obesity as Analyzed by the Response of Glucose Kinetics to Glucagon Infusion
Authors: Vranic Mladen , Morita Soichiro , Steiner George 
Published: September 2013

A new approach has been developed to examine insulin sensitivity and resistance in vivo in man. In it, tracer methods are used, which permit the assessment of nonsteady state glucose kinetics by a method that is noninvasive and does not use pharmacologic agents. Graded doses of glucagon, infused intravenously, are used to drive glucose out of steady state and to stimulate the release of insulin into the portal circulation. By relating the changes in the rates of glucose production, utilization, and fractional disappearance to immunoreactive glucagon and insulin, it is possible to assess the body's sensitivity to physiologic levels of these two hormones.
The utility of this approach was examined in obesity, a known human model of insulin resistance. The data demonstrated that glucose production in the obese subjects responded normally to glucagon. They also showed that insulin was much less effective in promoting glucose utilization in the obese persons than it was in the normal ones. In the obese subjects who were studied, the pancreatic B-cells were shown to be normally responsive to the stimulatory effects of either glucose or glucagon. Hence, they did not release sufficient insulin to overcome the insulin resistance, and these obese individuals had impaired glucose tolerance. Thus, it is suggested that, in the presence of insulin resistance, the responsiveness of B-cells will determine whether the glucose tolerance will be normal or abnormal in obese persons. This approach can now be used to explore glucose homeostasis in other conditions associated with glucose intolerance, the metabolic basis of which is undefined.
Ketonuria in Pregnancy—With Special Reference to Calorie-restricted Food Intake in Obese Diabetics
Authors: Coetzee E J , Jackson W P U , Berman P A 
Published: September 2013

Early morning ketonuria, as judged by Ketostix testing, occurred in 19% of urine samples from insulin-independent diabetic pregnant women eating 1000 calorie diets, in 14% from diabetics on higher calorie diets, and in 7% of urines from nondiabetic pregnant women. Ketostix test was never found to be positive in blood, even when it was 2+ in urine samples, and acetoacetate levels were always below 1 mmol/L.
Enzymatic estimations of acetoacetate (AA) and beta-hydroxybutyrate (BB) in urine and plasma samples revealed (1) no significant differences in range or mean between the groups receiving different restricted diets or full diets, the highest value observed for plasma AA being 0.34 mmol/L; (2) that Ketostix became positive at a concentration of AA above 1 mmol/L and that such a value in urine corresponded to plasma levels of between 0.06 and 0.1 mmol/L, i.e., double the normal; and (3) a 50–100-fold increase in urine AA when blood levels exceeded 0.08 mmol/L.
Neonates born to diabetic mothers with ketonuria had no fetal distress or asphyxia neonatorum. The lowest Apgar score at 5 min was 8; 80% of neonates had a score of 10. Hence, positive Ketostix tests in urine samples do not indicate toxic levels in the blood, and a 1000 calorie diet for obese pregnant diabetics appears to be safe as regards neonatal outcome.
Effects of Insulin and Pancreatic Polypeptide on Gastric Somatostatin Release
Authors: Chiba Tsutomu , Taminato Tomohiko , Kadowaki Seizo , Abe Hiromi , Chihara Kazuo , Matsukura Shigeru , Goto Yasuo , Seino Yutaka , Fujita Takuo 
Published: September 2013

Effects of arginine and such pancreatic hormones as insulin and pancreatic polypeptide on gastric somatostatin release from the isolated perfused rat stomach were studied. The stomach was isolated from a fasted rat by a modification of the method of Lefébvre and was perfused with 4.6% dextran Krebs-Ringer bicarbonate buffer containing 5.5 mM glucose. Both insulin and pancreatic polypeptide (10−10, 10−9, and 10−8 M) caused a significant decrease in gastric somatostatin secretion. Insulin (10 −10 M), furthermore, inhibited the glucagon (5 × 10−8 M)-induced somatostatin response. Arginine (10 and 19 mM) failed to elicit any significant change of somatostatin release.
These results suggest that gastric somatostatin release is affected by pancreatic hormones.
Physiologic Effects of Epinephrine on Glucose Turnover and Plasma Free Fatty Acid Concentrations Mediated Independently of Glucagon
Authors: Gray D E , Lickley H L A , Vranic M 
Published: September 2013

SUMMARY
It has been suggested that the effects of epinephrine on glucose production by the liver may be mediated through glucagon. To investigate this possibility, epinephrine (EPI) (0.2 or 0.1 μg/kg-min) was infused in 12 conscious normal dogs with or without somatostatin (ST) (0.05 μg/kg-min), a known inhibitor of glucagon and insulin release. EPI (0.2 μg/kg-min) induced a sustained hyperglycemia. This resulted from both an increase in glucose production, which rose initially to 45% above basal and then plateaued at suprabasal levels, and a small but noticeable reduction (18%) in the metabolic clearance rate of glucose. Plasma levels of both immunoreactive glucagon (IRG) and insulin (IRI) also increased transiently. ST plus EPI resulted in a more severe hyperglycemia, which was due to an exaggerated initial peak of glucose production. This response occurred despite a clear suppression (71%) of IRG below basal. ST blunted the initial EPI-induced IRI peak, but IRI never fell below basal with the combined infusion of EPI and ST. The blunting of this initial insulin peak may have affected the hyperglycemie response to EPI. The lower dose of EPI (0.1 μg/kg-min) had a similar but less definite effect on glucose regulation and caused both insulin and glucagon levels to rise. However, at the lower EPI dose, ST had no appreciable effect on insulin release (as judged by peripheral IRI levels), although IRG was again greatly suppressed. Neither the EPI-induced hyperglycemia nor the rapid rise in glucose production was affected by ST, suggesting that the EPI-induced hyperglycemia is not mediated through glucagon release. It also appears that elevated EPI levels can compensate for the role of basal glucagon in regulation of basal glucose production in the postabsorptive state. EPI induced a transient 120% rise in free fatty acid (FFA) levels. The rise in FFA was more marked and more sustained when ST was given together with EPI irrespective of whether the initial EPI-induced insulin peak was blunted or remained unaltered, thus indicating a possible effect of ST on EPI-induced lipoly-sis. The same low dose of ST (0.5 μg/kg-min) infused without EPI greatly suppressed both IRG and IRI below basal (60%).
Thus (1) EPI infusion induced sustained hyperglycemia, resulting from a transient increase in glucose production and an inhibition of metabolic clearance of glucose; both IRG and IRI were also transiently increased. (2) The effect of EPI on glucose production was independent of glucagon, but it was possibly enhanced by suppression of the initial insulin peak. (3) A low dose of ST, which, by itself, suppressed basal IRI and IRG release, was able to override the effect of EPI on IRG but not on IRI release. Thus, the effect of a selective glucagon suppression could be studied. (4) EPI increased plasma FFA only transiently. (5) ST may directly or indirectly increase the lipolytic effect of EPI.
The Role of Hypoinsulinemia in Exercise Metabolism
Authors: Issekutz B 
Published: September 2013

SUMMARY
Dogs with indwelling catheters in the jugular vein and in the carotid artery ran on a treadmill (15% slope, 90 m/min). Hepatic glucose production (Ra), glucose utilization (Rd), and the metabolic clearance rate (MCR) of glucose were measured according to the primed constant rate infusion tracer techniques using 3-3H-glucose as tracer. In addition, plasma insulin (IRK) and glucagon (IRG) levels were determined. In 60 min, exercise increased Ra from 3.8 ± 0.3 to 8.5 ± 0.9 mg/kg min and MCR from 4.0 ± 0.2 to 10.4 ± 0.8 ml/kg min. Plasma insulin declined from 11.4 ± 1.2 to 7.9 ± 0.6 μ-U/ml and glucagon rose from 70 ± 10 to 110 ± 12 pg/ml. After 1 h, after a priming dose (0.36 g/kg), mannoheptulose was infused (6 mg/kg min) for 60 min. IRI fell to 3.4 μU/ml and IRG did not change significantly. Ra rose about 100% (to 16.3 ± 2.1 mg/kg min) and plasma glucose increased from 97 ± 2 to 200 ± 21 mg/dl followed by a slow rise of Rd. The MCR showed a transient decline from 10.3 ± 0.8 to 8.3 ± 1.5 ml/kg min. After that, it did not differ significantly from controls. These effects could be prevented by the infusion of insulin (0.1 mU/kg min). There was a significant inverse correlation between the logarithm of Ra and that of IRI (r = 0.83) and an even stricter correlation between Ra and the logarithm of the molar ratio of IRG/IRI (r = 0.96). It is concluded that the main role of exercise-induced hypoinsulinemia is to increase hepatic glucose production by increasing the sensitivity of the liver to glucagon. Glucose utilization of the working muscle is dominated by the increased activity of hexokinase (s), and physiologic changes of plasma insulin have little effect On it.
Cytotoxic Activation of Complement by Mouse Pancreatic Islet Cells
Authors: Idahl Lars-Åke , Sehlin Janove , Täljedal Inge-Bert , Thornell Lars-Eric 
Published: September 2013

SUMMARY
Human serum, or serum proteins excluded by Sephadex G-25, irreversibly inhibited the ability of mouse pancreatic islet cells to accumulate Rb+. The same treatment reduced the capacity of serum to subsequently inhibit Rb+ uptake by fresh islet cells or to lyse sensibilized sheep erythrocytes. Serum-treated islet cells exhibited electron microscopic signs of damage, including ruptures of the plasma membrane, swelling of mitochondria, and reduced electron density of the cytoplasmic ground substance. Serum induced a prompt insulin release, which was not inhibited by epinephrine. The serum effects were prevented by mild heating (50°C or 56°C, 30 min) but not by treating serum with 10 mM EGTA and 10 mM MgCl2, or with soybean trypsin inhibitor. Inhibition of Rb+ accumulation in response to human serum was also observed with dispersed mouse exocrine pancreas, liver, and spleen cells but not with whole islets. Homologous mouse serum had no effect on mouse liver or spleen cells but significantly decreased the Rb+ uptake by mouse islet cells. Autologous serum had no noticeable effect. It is suggested that mouse islet cells can activate complement via the alternative pathway and that triggering of this pathway is controlled by cellular discriminators of species, organ, and self.
Studies on the Insulin Mediator: II. Separation of Two Antagonistic Biologically Active Materials from Fraction II
Authors: Cheng Kang , Galasko Gail , Huang Laura , Kellogg Joan , Larner Joseph 
Published: September 2013

SUMMARY
Insulin treatment significantly altered the elution profile of deproteinized muscle extracts chromato-graphed on Sephadex G-25 columns, particularly in fraction II, which contains the insulin mediator. Further purification of fraction II by high-voltage paper electrophoresis at pH 1.9 and 3.5 resulted in two active fractions. Fraction 1 → 4 stimulated the cyclic AMP-dependent protein kinase and inhibited glycogen synthase phosphoprotein phosphatase, and may be a novel substance. Fractions 1 → &gt; 6 and 3 → 6 inhibited the cyclic AMP-dependent protein kinase and stimulated glycogen synthase phosphatase. It is proposed that the insulin mediator is present in fractions 1 → 6 and 3 → 6.
Rapid Changes in Calcium Content of Rat Pancreatic Islets in Response to Glucose
Authors: Ribes Gerard , Siegel Eberhard G , Wollheim Claes B , Renold Albert E , Sharp Geoffrey W G 
Published: September 2013

To study whether glucose affects total islet Ca content, 45Ca content was measured in isolated pancreatic islets, loaded with 45Ca++, during up to 48 h in tissue culture conditions. In islets maintained in 2.8 mM or 8.3 mM glucose the 45Ca content did not increase further after 24 h, indicating that, at this time point, islets are in isotopie equilibrium. Islets maintained in 8.3 mM glucose had a significantly higher Ca content of 9 pmol/islet than the 5 pmol of islets maintained in 2.8 mM glucose.
An increase in the glucose concentration from 2.8 mM to 8.3 mM after 24 h, in the continued presence of 45Ca++, caused a significant and rapid augmentation of the Ca content (+ 2.5 pmol/islet/5 min). Conversely, a decrease of the glucose concentration from 8.3 mM to 2.8 mM resulted in a rapid loss of cellular Ca. Thus, glucose rapidly affects the total Ca content of islets, the turnover of Ca amounting to approximately 10% of the total content per minute.
Islets maintained in 8.3 mM glucose for 24 h exhibited a greater insulin release in response to 16.7 mM glucose than islets maintained for 24 h in 2.8 mM glucose. The increased response, however, was not correlative with the difference in Ca content.
Correlation Between the Nature and Amount of Carbohydrate in Meal Intake and Insulin Delivery by the Artificial Pancreas in 24 Insulin-dependent Diabetics
Authors: Slama Gérard , Klein Jean-Claude , Delage Anne , Ardila Enrique , Lemaignen Hervé , Papoz Laure , Tchobroutsky Georges 
Published: September 2013

We have studied the effects of mixed meals and dextrose intake on blood glucose and insulin delivery by the artificial pancreas in 24 insulin-dependent diabetics. A group of 12 patients had 3 mixed meals containing at random 20, 40, and 60 g of complex carbohydrate along with protein and fat; another group of 12 diabetics, comparable in weight, age, and duration of diabetes, received at random 20, 40, and 60 g of dextrose.
Dextrose ingestion led to a higher initial blood glucose increase than did the mixed meal, but the duration of blood glucose increase lasted significantly longer after the mixed meal than after the dextrose load. The areas under the curves of hyperglycemia were not significantly different. There was a high (but not linear) correlation between the total amount of insulin delivered in order to restore initial blood glucose values and the amount of CHO consumed. There was no correlation with age, body weight, duration of diabetes, nor with the nature and order of administration of the CHO load; 5.1 ± 1.6 to 13.7 ± 2.1 units of insulin were needed for a period of 94 ± 11 to 132 ± 11 min. It is suggested that some of the data obtained in this study might be useful in the programming of an open-loop insulin infusion system.